World Wide Fund For Nature

World Wide Fund for Nature
From Wikipedia, the free encyclopedia
Abbreviation WWF
Motto Building a future in which people and nature thrive.
Formation 29 April 1961; 55 years ago a
Bernhard of Lippe-Biesterfeld b
Founders
Prince Philip, Duke of Edinburgh
Julian Huxley [1]
Max Nicholson
Peter Scott
Guy Mountfort
Godfrey A. Rockefeller [2][citation needed]
Type Charitable trust
Purpose Environmentalism
Conservation
Ecology
Headquarters Avenue du Mont-Blanc,
Gland, Vaud, Switzerland
Coordinates 46.4171864°N 6.2709482°E
Region Worldwide
Methods Lobbying
Research
Consultancy
Key people  Prince Philip, Duke of

Edinburgh, President Emeritus
 Yolanda Kakabadse, President
 Marco Lambertini, Director General
Revenue(2010[3]) € 654 million (2013)
Slogan "For a Living Planet"
Website worldwildlife.org
panda.org
a
First office opened 11 September 1961 in Morges,
Switzerland.
b
Also the WWF's first president.[4]
Earth Hour 2013 at the Verona Arena amphitheatre,Piazza Bra, Verona, Italy before (top) and while the street lighting was
switched off.
The World Wide Fund for Nature (WWF) is an international non-governmental organization founded in

1961, working in the field of the wilderness preservation, and the reduction of humanity's footprint on
the environment. It was formerly named theWorld Wildlife Fund, which remains its official name
in Canada and the United States.
It is the world's largest conservation organization with over 5 million supporters worldwide, working in more
than 100 countries, supporting around 1,300[5] conservation and environmental projects. WWF is a
foundation,[6] with 55% of funding from individuals and bequests, 19% from government sources (such as
the World Bank, DFID, USAID) and 8% from corporations in 2014.[3]
The group's mission is "to stop the degradation of the planet’s natural environment and to build a future in
which humans live in harmony with nature."[7] Currently, much of its work focuses on the conservation of
three biomes that contain most of the world'sbiodiversity: oceans and coasts, forests,
and freshwater ecosystems. Among other issues, it is also concerned with endangered species,
sustainable production of commodities and climate change.
Contents
[hide]
 1The Conservation Foundation

 2Morges Manifesto
 3Later history
 4Panda symbol
 521st century
 6Publications
o 6.1Policy-making
 7Controversies
o 7.1Corporate partnerships
o 7.2Project "Lock"
o 7.3Mekong River dolphins report
o 7.4Pandaleaks
o 7.5ARD documentary
o 7.6Hunting
o 7.7Alleged human-rights abuses
 8Presidents
 9The 1001: A Nature Trust
 10WWF initialism dispute
 11WWF in music
 12Notable programs and campaigns
 13Global initiatives
 14See also
 15References
 16External links
The Conservation Foundation[edit]

The Conservation Foundation, a precursor to WWF, was founded in 1947 by Fairfield Osborn in New
York City in support of capitalism-friendly ecological practices. The advisory council included leading
scientists such as Charles Sutherland Elton, G Evelyn Hutchinson, Aldo Leopold, Carl Sauer, and Paul
Sears.[8] It supported much of the scientific work cited by Rachel Carson's Silent Spring, including that
of John L. George, Roger Hale, Robert Rudd, and George Woodwell.
In 1963, the Foundation held a conference and published a major report warning of anthropogenic global
warming, written byNoel Eichhorn based on the work of foundation vice-president Frank Fraser
Darling, Edward Deevey, Erik Eriksson, Charles Keeling, Gilbert Plass, Lionel Walford, and William
Garnett.[9]
In 1990, the Conservation Foundation was merged into WWF, after becoming an affiliate of WWF in 1985,
when it became a distinct legal entity but with the same staff and board. The organization now known as
the Conservation Foundation in the United States is the former Forest Foundation of DuPage County.[10][11]
Morges Manifesto[edit]
The idea for a fund on behalf of endangered animals was initially proposed by Victor Stolan to Sir Julian
Huxley in response to articles he published in the British newspaper The Observer. This proposal led
Huxley to put Stolan in contact with Max Nicholson, a person who had had thirty years experience of
linking progressive intellectuals with big business interests through the Political and Economic
Planning think tank.[1][12][13] Nicholson thought up the name of the organization. WWF was conceived on 29
April 1961, under the name of World Wildlife Fund, and its first office was opened on 11 September that
same year in Morges, Switzerland. WWF was conceived to act as a funding institution for existing
conservations groups such as the International Union for the Conservation of Nature and Natural
Resources and The Conservation Foundation.[10]Godfrey A. Rockefeller also played an important role in its
creation, assembling the first staff.[2] Its establishment marked with the signing of the "Morges Manifesto",
[14]
the founding document that sets out the fund's ideology.
The WWF hot air balloon in Brazil
...They need above all money, to carry out missions and to meet conservation emergencies by buying land
where wildlife treasures are threatened, money, for example, to pay guardians of wildlife refuges ...for
educations among those who would care... For sending experts to danger spots and training... Making it all
possible that their needs are met before it is too late.
— Morges Manifesto
Later history[edit]
WWF has set up offices and operations around the world. It originally worked by fundraising and providing
grants to existing non-governmental organizations, based on the best-available scientific knowledge and
with an initial focus on the protection ofendangered species. As more resources became available, its
operations expanded into other areas such as the preservation of biological diversity, sustainable use
of natural resources, the reduction of pollution, and climate change. The organization also began to run its
own conservation projects and campaigns, and by the 1980s started to take a more strategic approach to
its conservation activities.
In 1986, the organization changed its name to World Wide Fund for Nature, while retaining the WWF
initials. However, it continued at that time to operate under the original name in the United States and
Canada.[7]
That year was the 25th anniversary of WWF's foundation, an event marked by a gathering in Assisi, Italy to
which the organization's International President HRH Prince Philip, the Duke of Edinburgh, invited religious
authorities representing Buddhism, Christianity, Hinduism, Islam and Judaism. These leaders produced
The Assisi Declarations, theological statements showing the spiritual relationship between their followers
and nature that triggered a growth in the engagement of those religions with conservation around the world.
[15]
In the 1990s, WWF revised its mission statement to:

Stop the degradation of the planet's natural environment and to build a future in which humans live in
harmony with nature, by:
 conserving the world's biological diversity;

 ensuring that the use of renewable natural resources is sustainable;
[and]
 promoting the reduction of pollution and wasteful consumption.
WWF scientists and many others identified 238 ecoregions that represent the world's most biologically
outstanding terrestrial, freshwater and marine habitats, based on a worldwide biodiversity analysis which
the organization says was the first of its kind. [16] In the early 2000s (decade), its work was focused on a
subset of these ecoregions, in the areas of forest, freshwater and marine habitat conservation, endangered
species conservation, climate change, and the elimination of the most toxic chemicals.
"We shan't save all we should like to, but we shall save a great deal more than if we had never tried." –
Sir Peter Scott [17]
In 1996, the organization obtained general consultative status from UNESCO.
Panda symbol[edit]
The giant panda has become the symbol of WWF.
WWF's giant panda logo originated from a panda named Chi Chi that had been transferred from Beijing
Zoo to London Zoo in 1958, three years before WWF became established. The logo was founded by
Young and was founded in 1966. Being famous as the only panda residing in the Western world at that
time, its uniquely recognisable physical features and status as an endangered species were seen as ideal
to serve the organization's need for a strong recognisable symbol that would overcome all language
barriers.[18] Moreover, the organization also needed an animal that would have an impact in black and white
printing. The logo was then designed by Sir Peter Scottfrom preliminary sketches made by Gerald
Watterson, a Scottish naturalist.[19][20] However the logo shown on this page is not the logo designed by Peter
Scott but a later one, designed for WWF when it changed its name from World Wildlife Fund to World Wide
Fund for Nature.[citation needed]
21st century[edit]
WWF's strategy for achieving its mission specifically focuses on restoring populations of
36 species (species or species groups that are important for their ecosystem or to people,
including elephants, tunas, whales, dolphins and porpoises), and ecological footprint in 6 areas (carbon
emissions, cropland, grazing land, fishing, forestry and water). [citation needed]
The organization also works on a number of global issues driving biodiversity loss and unsustainable use of
natural resources, including finance, business practices, laws, and consumption choices. Local offices also
work on national or regional issues.[21]
WWF works with a large number of different groups to achieve its goals, including other NGOs,
governments, business, investment banks, scientists, fishermen, farmers and local communities. It also
undertakes public campaigns to influence decision makers, and seeks to educate people on how to live in a
more environmentally friendly manner.It urges people to donate funds to protect the environment. The
donors can also choose to receive gifts in return.[citation needed]
Publications[edit]
WWF publishes the Living Planet Index in collaboration with the Zoological Society of London. Along
with ecological footprint calculations, the Index is used to produce a bi-yearlyLiving Planet Report giving an
overview of the impact of human activity on the world.[22]
The organization also regularly publishes reports, fact sheets and other documents on issues related to its
work, in order to raise awareness and provide information to policy and decision makers. [23]
Policy-making[edit]
Policies of the WWF are made by the board members who are elected for three- year terms. The Executive
Team guides and develops WWF's strategy. There is also a National Council which stands as an advisory
group to the board and finally a team of scientists and experts in conservation who research for WWF.
National and international law plays an important role in determining how habitats and resources are
managed and used. Laws and regulations become one of the organization’s global priorities.
The WWF has been opposed to the extraction of oil from the Canadian tar sands and has campaigned on
this matter. Between 2008 and 2010 the WWF worked with The Co-operative Group, the UK's
largest consumer co-operative to publish reports which concluded that: (1) exploiting the Canadian tar
sands to their full potential would be sufficient to bring about what they described as 'runaway climate
change;[24] (2) carbon capture and storage (CCS) technology cannot be used to reduce the release of
carbon dioxide into the atmosphere to a level comparable to that of other methods of oil extraction; [25] (3) the
$379 billion which is expected to be spent extracting oil from tar sands could be better spent on research
and development in renewable energy technology; [26] and (4) the expansion of tar sands extraction poses a
serious threat to the caribou in Alberta .[27]
The organization convinces and helps governments and other political bodies to adopt, enforce, strengthen
and/or change policies, guidelines and laws that affect biodiversity and natural resource use. It also
ensures the governments to consent and/or keeps their commitment to international instruments relating to
the protection of biodiversity and natural resources.[28][29]
In 2012, David Nussbaum, Chief Executive of WWF-UK, spoke out against the way shale gas is used in the
UK, saying: "...the Government must reaffirm its commitment to tackling climate change and prioritise
renewables and energy efficiency." [30]
Controversies[edit]
Corporate partnerships[edit]
WWF has been accused by the campaigner Corporate Watch of being too close to businesses to campaign
objectively.[31][32] WWF claims partnering with corporations such asCoca-Cola, Lafarge, Carlos Slim's
and IKEA will reduce their effect on the environment.[33] WWF received €56 million (US$80 million) from
corporations in 2010 (an 8% increase in support from corporations compared to 2009), accounting for 11%
of total revenue for the year.[3]
Project "Lock"[edit]
In 1988, Prince Bernhard, previously WWF's first President, sold paintings for GBP 700,000 to raise money
for the World Wildlife Fund. The money was deposited in a Swiss WWF bank account. In 1989, Charles de
Haes, then WWF Director-General, transferred GBP 500,000 back to Bernhard for what he (de Haes)
called a "private project". It was then revealed, in 1991, that Prince Bernhard had used the money to hire
KAS International, owned by SAS founder David Stirling, for an operation called Project "Lock" during
whichmercenaries (mostly British) fought poachers in nature reserves.[34]
Mekong River dolphins report[edit]

In June 2009, Touch Seang Tana, chairman of Cambodia's Commission for Conservation and
Development of the Mekong River Dolphins Eco-tourism Zone, charged that the WWF had misrepresented
the danger of extinction of the Mekong dolphin in order to boost fundraising.[35] The report stated that the
deaths were caused by a bacterial disease that became fatal due to environmental contaminants
suppressing the dolphins' immune systems.[36] He called the report unscientific and harmful to the
Cambodian government and threatened the WWF's Cambodian branch with suspension unless they met
with him to discuss his claims.[37] Touch Seang Tana later said he would not press charges of supplying
false information and would not make any attempt to prevent WWF from continuing its work in Cambodia,
but advised WWF to adequately explain its findings and check with the commission before publishing
another report. After this, in January 2012, Touch Seang Tana signed the "Kratie Declaration on the
Conservation of the Mekong River Irrawaddy Dolphin" along with WWF and the Cambodian Fisheries
Administration, an agreement binding the parties to work together on a "roadmap" addressing dolphin
conservation in the Mekong River.[38]
Pandaleaks[edit]
In 2012, German investigative journalist Wilfried Huissmann published a book called "The Silence of the
Pandas". It became a bestseller in Germany, but was banned from Britain until 2014, when it was released
under the title of "Pandaleaks", after a series of injunctions and court orders. [39] The book criticizes WWF for
its supposed involvement with corporations that are responsible for large-scale destruction of the
environment, such as Coca-Cola, and gives details into the existence of the secret 1001 Club, whose
members, Huismann claims, continue to have an unhealthy influence on WWF's policy making. [39] However,
WWF has sought to deny the allegations made against it. [40]
ARD documentary[edit]
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message)
The German public television ARD aired a documentary on 22 June 2011 that claimed to show how the
WWF cooperates with corporations such as Monsanto, providing sustainability certification in exchange for
donations – essentially greenwashing.[41] WWF has denied the allegations.[42] By encouraging high-impact
eco-tourism, the program alleges that WWF contributes to the destruction of habitat and species it claims to
protect. WWF-India is not active at the tiger reserve given as the example, [citation needed] but it is active elsewhere
seeking to limit adverse tourism effects and better sharing of tourism benefits to local communities. The
program also alleges WWF certified a palm oil plantation operated by Wilmar International, a Singaporean
company, on the Indonesian island of Borneo, even though the establishment of the plantation led to the
destruction of over 14,000 hectares of rainforest. Only 80 hectares were ultimately conserved, the ARD
documentary claims. According to the programme, two orangutans live on the conserved land, but have
very slim chances of survival because no fruit trees remain and the habitat is too small to sustain them. To
survive, they steal palm nuts from the neighbouring plantation, thereby risking being shot by plantation
workers. WWF notes that the plantation filmed is PT Rimba Harapan Sakti, which has not been certified as
a sustainable producer by theRound Table on Sustainable Palm Oil. Aerial photographs show that around
4000 hectares, or about a third of the forest cover, has been conserved. [citation needed]
Hunting[edit]
The President of Honor of WWF in Spain used to be King Juan Carlos I,[43] who has been a known hunting
enthusiast. In 1962, when he was 24 years old, he was invited by the German Baron Werner von
Alvensleben to a hunt in Mozambique.[44] Since then, the king has taken part in hunting forays
in Africa and Eastern Europe. In October 2004, he was a member of a hunt in Romania that killed
a wolf and nine brown bears, including one that was pregnant, according to the Romanian
newspaper Romania Libera.[45] He was also accused by a Russian official of killing a bear called Mitrofan,
supposedly after giving vodka to the animal, in an episode that sparked controversy in Spain, although the
claim was never proven.[46] In the same year, according to The Guardian, the Polish government allowed
him to kill a European bison in Białowieża Forest, even though it is an endangered species.[47] Further
controversy arose in April 2012 when the king's participation in an elephant hunt in Botswana was
discovered only after he returned to Spain on an emergency flight after tripping over a step and fracturing
his hip.[48] Many Spanish environmental groups and leftist parties criticized the monarch's hobby,[49] and the
WWF stripped him of the honorary position in July 2012, in an extraordinary assembly by 94% of the votes
of the members.[50]
Prince Charles, the UK head of the WWF,[51] has stated that he enjoys hunting.[52] He is believed, however,
to adhere to legal British traditional hunting and speaks out against hunting endangered species. [citation needed]
Alleged human-rights abuses[edit]

In a 2016 complaint to the Organisation for Economic Co-operation and Development (OECD), The
nonprofit group Survival International accused WWF of inadvertently facilitating serious human-rights
abuses against indigenous pygmy inhabitants of the rainforest in Cameroon. The complaint alleged that
"anti-poaching eco-guards who were part-funded and logistically helped by WWF, victimised the hunter
gatherer Baka people, razed to the ground their camps, destroyed or confiscated their property, forced
them to relocate and have regularly used physical force and threats of violence against them". [53] It was the
first such complaint to be made against a conservation group. The complaint alleges that WWF violated
OECD guidelines for the conduct of multinational companies and the UN Declaration of human rights.
WWF responded saying that eco-guards were for the most part "protecting the integrity and resources of a
[forest] zoning system that includes community forests, hunting and access zones vital to Baka
communities." The group disclaimed knowledge of any direct involvement by its staff in rights abuses. [53]
Survival International has also accused WWF of violating its own policies regarding indigenous people's
rights by forming a partnership with French logging company Rougier, which it says is responsible for large
areas of deforestation in southeast Cameroon, illegally and without the consent of local Baka tribespeople.
[54]
WWF France stated in 2015 that it had entered a "three-year strategic collaboration" with the Rougier
Group.[55]
Presidents[edit]
Prince Bernhard of Lippe-Biesterfeld in 1942.
Years Name
1961–1976 Prince Bernhard of Lippe-Biesterfeld
1976–1981 John Hugo Loudon
1981–1996 Prince Philip, Duke of Edinburgh
1996–1999 Syed Babar Ali
2000 Ruud Lubbers
2000–2001 Sara Morrison
2001–2010 Chief Emeka Anyaoku
2010–
Yolanda Kakabadse
present
Source: WWF Presidents
The 1001: A Nature Trust[edit]

Main article: The 1001: A Nature Trust
In the early 1970s, Prince Bernhard, Prince Philip, Duke of Edinburgh and a few associates set up the The
1001: A Nature Trust to handle the WWF's administration and fund-raising. 1001 members each
contributed $10,000 to the trust.[17]
WWF initialism dispute[edit]
See also: WWE § Legal disputes
In 2000, the World Wide Fund for Nature sued the World Wrestling Federation (now named WWE) for
unfair trade practices. Both parties had shared the initials "WWF" since 1979. The conservation
organization claimed that the sports entertainment company had violated a 1994 agreement regarding
international use of the WWF initials.[56][57]
On August 10, 2001, a U.K. court ruled in favour of the World Wide Fund for Nature. The World Wrestling
Federation filed an appeal in October 2001. However, on May 10, 2002, the World Wrestling Federation
changed its Web address from WWF.com to WWE.com, and replaced every "WWF" reference on the
existing site with "WWE", as a prelude to changing the company's name to "World Wrestling
Entertainment." Its stock ticker also switched from WWF to WWE.
Abandonment of the initialism did not end the two organizations' legal conflict. Later in 2002, the World
Wide Fund for Nature petitioned the court for $360 million in damages, but was not successful. A
subsequent request to overturn by the World Wide Fund for Nature was dismissed by the British Court of
Appeal on June 28, 2007. In 2003, World Wrestling Entertainment won a limited decision which permitted
them to continue marketing certain pre-existing products with the abandoned WWF logo. However, WWE
was mandated to issue newly branded merchandise such as apparel, action figures, video games,
and DVDs with the "WWE" initials. Additionally, the court order required the company to remove both
auditory and visual references to "WWF" in its library of video footage outside the United Kingdom.
Starting with the 1,000th episode of Raw in July 2012, the WWF "scratch" logo is no longer censored in
archival footage. In addition, the WWF initials are no longer censored when spoken or when written in plain
text in archival footage. In exchange, WWE is no longer permitted to use the WWF initials or logo in any
new, original footage, packaging, or advertising, with any old-school logos for retro-themed programming
now using the original WWF logo, but modified without the F.
WWF in music[edit]
No One's Gonna Change Our World was a charity album released in 1969, for the benefit of the WWF.
Peter Rose and Anne Conlon are music theatre writers, well known for their environmental musicals for
children, who were commissioned by WWF-UK to write several environmental musicals as part of an
education plan. Some were narrated by David Attenborough, and broadcast on television in numerous
countries.
The British pop group S Club 7 were ambassadors for WWF-UK during their time together as a band
(1999-2003). Each of the members sponsored an endangered animal, and in 2000, they traveled to the
various locations around the world of their chosen animals for a seven part BBC documentary series
entitled S Club 7 Go Wild.
Environmentally Sound: A Select Anthology of Songs Inspired by the Earth is a benefit album released in
2006, for WWF-Philippines, featuring artists that included Up Dharma Down, Radioactive Sago
Project, Kala, Cynthia Alexander, and Joey Ayala.[58]
In June 2012, WWF launched an online music download store with fairsharemusic from which 50% of the
profit goes to the charity.
In April 2015, Hailey Gardiner released her solo EP, titled The Woods. In honor of Earth Day, 15% of the
proceeds made towards the purchase of the EP would be donated to the WWF.
Notable programs and campaigns[edit]

 Debt-for-Nature Swap
 Earth Hour
 Healthy Grown
 Marine Stewardship Council
Global initiatives[edit]
Since 2008, through its Global Programme Framework (GPF), WWF has said it is focusing its efforts on
thirteen global initiatives:[59]
 Amazon
 Arctic
 China for a Global Shift
 Climate and Energy
 Coastal East Africa
 Coral Triangle
 Forest and Climate
 Green Heart of Africa
 Heart of Borneo
 Living Himalayas
 Market Transformation
 Smart Fishing
 Tigers
See also[edit]
 Centres of Plant Diversity
 Conservation movement
 Environmental movement
 Eugene Green Energy Standard, founded by the WWF.
 Global 200, ecoregions identified by the WWF as priorities for
conservation.
 Natural environment
 Sustainability
 Sustainable development
 TRAFFIC, the wildlife trade monitoring network, a joint programme of
WWF and the International Union for Conservation of Nature (IUCN).
 World Conservation Award, created in conjunction with the WWF.
 West Coast Environmental Law
 Environmental Dispute Resolution Fund
 List of environmental organizations
References[edit]
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London: Telegraph.co.uk. Retrieved 2012-08-19.
51. Jump up^ Press Association (2011-09-08). "Prnce Charles -
President of UK WWF". London: Guardian. Retrieved 2012-08-19.
52. Jump up^ Stephen Bates (2004-11-06). "Charles enjoys hunting".
London: Guardian. Retrieved2012-08-19.
53. ^ Jump up to: Vidal, John (3 March 2016). "WWF accused of facilitating
a b
human rights abuses of tribal people in Cameroon". The Guardian.

54. Jump up^ "WWF partners with logging company destroying 'Pygmy'
land". Survival International. 25 May 2016.
55. Jump up^ "WWF France and Rougier to jointly advance responsible
forest management and trade" (Press release). WWF. 9 April 2015.
56. Jump up^ InternetNews Realtime IT News – Wildlife Fund Pins
Wrestling Federation ArchivedNovember 14, 2006, at the Wayback
Machine.
57. Jump up^ Text of the 1994 legal agreement with the World Wrestling
Federation ArchivedOctober 13, 2006, at the Wayback Machine.
58. Jump up^ "The Harmonics of being Environmentally Sound". World
Wildlife Fund - Philippines. 18 August 2006. Retrieved 2010-06-30.
59. Jump up^ WWF Global Initiatives
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WWF in Brief
What is WWF?
 WWF is one of the world's largest conservation organizations.
 It was conceived on the 29th April 1961.
 Its first office opened in September 1961 in the Swiss town of Morges.
 The central secretariat for the network - called WWF International - is
now located in Gland, Switzerland (organizational structure)
 WWF is an independent foundation registered under Swiss law.
 The organization has offices in more than 80 countries around the world.
 It employs around 6,200 full time staff
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 WWF originally stood for "World Wildlife Fund".
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International Union for Conservation of Nature

International Union for Conservation of Nature and Natural

Resources (IUCN)
Founded October 1948, Fontainebleau,France
Type International organization
Focus Nature conservation, biodiversity
Rue Mauverney 28, 1196 Gland,Switzerland

Location
Area served Worldwide
Members 1218
Key people Inger Andersen (Director General)
Zhang Xinsheng (President)
Revenue CHF 114 million / US$ 116 million (2013)
Employees Over 1,000 (worldwide)
Volunteers 11,000
Mission "Influence, encourage and assist societies throughout the world
to conserve the integrity and diversity of nature and to ensure
that any use of natural resources is equitable and ecologically
sustainable."[1]
Website www.iucn.org
The International Union for Conservation of Nature and Natural Resources (IUCN) is an international

organization working in the field of nature conservation and sustainable use of natural resources. It is
involved in data gathering and analysis, research, field projects, advocacy, lobbying and education. IUCN's
mission is to "influence, encourage and assist societies throughout the world to conserve nature and to
ensure that any use of natural resources is equitable and ecologically sustainable."
Over the past decades, IUCN has widened its focus beyond conservation ecology and now incorporates
issues related to gender equality, poverty alleviation and sustainable business in its projects. Unlike other
international NGOs, IUCN does not itself aim to mobilize the public in support of nature conservation. It
tries to influence the actions of governments, business and other stakeholders by providing information and
advice, and through lobbying and partnerships. The organization is best known to the wider public for
compiling and publishing the IUCN Red List, which assesses the conservation status of species worldwide.
[2]
IUCN has a membership of over 1200 governmental and non-governmental organizations. Some 11,000
scientists and experts participate in the work of IUCN commissions on a voluntary basis. It employs
approximately 1000 full-time staff in more than 60 countries. Its headquarters are in Gland, Switzerland.[2]
IUCN has observer and consultative status at the United Nations, and plays a role in the implementation of
several international conventions on nature conservation and biodiversity. It was involved in establishing
the World Wide Fund for Nature and the World Conservation Monitoring Centre. In the past, IUCN has
been criticized for placing the interests of nature over those of indigenous peoples. In recent years, its
closer relations with the business sector have caused controversy. [3][4]
IUCN was established in 1948. It was previously called the International Union for Protection of Nature
(1948–1956) and the World Conservation Union (1990–2008).
Contents
[hide]
 1History
o 1.1Overview
o 1.2Timeline
 2Current work
o 2.1Workprogram 2013–2016
o 2.2Habitats and species
o 2.3Business partnerships
o 2.4National and international policy
 3Organizational structure
o 3.1Members
o 3.2Commissions
o 3.3Secretariat
 4Governance and funding
o 4.1Governance
o 4.2Funding
 5Influence and criticism
o 5.1Influence
o 5.2Criticism
 6Publications
 7See also
 8Footnotes
 9References
History[edit]
[nb 1]
Overview[edit]
Establishment[5]
In 1947, the Swiss League for the Protection of Nature organised an international conference on
the protection of nature in Brunnen (Switzerland).[6] Afterwards, the IUCN was established on 5 October
1948, in Fontainebleau, France, when representatives of governments and conservation organizations
signed a formal act constituting the International Union for Protection of Nature (IUPN). It is considered to
be the first government-organized non-governmental organization. The initiative to set up the new
organisation came fromUNESCO and especially from its first Director General, the British biologist Julian
Huxley.
Julian Huxley, the first Director General of UNESCO, took the initiative to set up IUCN
The objectives of the new Union were to encourage international cooperation in the protection of nature, to
promote national and international action and to compile, analyse and distribute information. At the time of
its founding IUPN was the only international organisation focusing on the entire spectrum of nature
conservation (an international organisation for the protection of birds, now BirdLife International, had been
established in 1922.)
Early years: 1948–1956[7]
IUPN started out with 65 members. Its secretariat was located in Brussels. Its first work program focused
on saving species and habitats, increasing and applying knowledge, advancing education, promoting
international agreements and promoting conservation. Providing a solid scientific base for conservation
action was the heart of all activities; commissions were set up to involve experts and scientists.
IUPN and UNESCO were closely associated. They jointly organized the 1949 Conference on Protection of
Nature (Lake Success, USA). In preparation for this conference a list of gravely endangered species was
drawn up for the first time, a precursor of the IUCN Red List of Threatened Species. In the early years of its
existence IUPN depended almost entirely on UNESCO funding and was forced to temporarily scale down
activities when this ended unexpectedly in 1954.
IUPN was successful in engaging prominent scientists and identifying important issues such as the harmful
effects of pesticides on wildlife but not many of the ideas it developed were turned into action. This was
caused by unwillingness to act on the part of governments, uncertainty about the IUPN mandate and lack
of resources. In 1956, IUPN changed its name to International Union for Conservation of Nature and
Natural Resources.
Increased profile and recognition: 1956–1965[8]
In the 1950s and 1960s Europe entered a period of economic growth and formal colonies became
independent. Both developments had impact on the work of IUCN. Through the voluntary (i.e. pro bono)
involvement of experts in its Commissions IUCN was able to get a lot of work done while still operating on a
low budget. It expanded its relations with UN-agencies and established links with the Council of Europe. In
1961, at the request of ECOSOC, the United Nations Economic and Social Council, IUCN published the
first global list of national parks and protected areas which is has updated ever since. IUCN's best known
publication, the Red Data Book on the conservation status of species, was first published in 1964.
IUCN began to play a part in the development of international treaties and conventions, starting with
the African Convention on the Conservation of Nature and Natural Resources. Environmental law and
policy making became a new area of expertise.
Africa was the first regional focus of IUCN conservation action
Africa was the focus of many of the early IUCN conservation field projects. IUCN supported the
‘Yellowstone model’ of protected area management, which severely restricted human presence and activity
in order to protect nature. IUCN and other conservation organisations were criticized for protecting nature
against people rather than with people. This model was initially also applied in Africa and played a role in
the decision to remove the Maasai people from Serengeti National Park and the Ngorongoro Conservation
Area.[3]
To establish a stable financial basis for its work, IUCN participated in setting up the World Wildlife Fund
(1961) (now theWorld Wide Fund for Nature WWF). WWF would work on fundraising, public relations, and
increasing public support. IUCN would continue to focus on providing sound science and data, and
developing ties with international bodies. Funds raised by WWF would be used to cover part of the
operational costs of IUCN. Also in 1961, the IUCN headquarters moved from Belgium to Morges in
Switzerland.
Consolidating its position in the international environmental movement: 1966–1975 [9]
Public concerns about the state of the environment in the sixties and seventies led to the establishment of
new NGOs, some of which (e.g. Greenpeace and Friends of the Earth) also worked globally. Many of these
new organisations were more activist and critical of government than IUCN which remained committed to
providing science-based advice to governments. As a result, IUCN was criticized by some as being old-
fashioned and irrelevant.
IUCN’s membership still grew (from 200 in 1961 to 400 in 1974) and its formal standing and influence
increased. A grant from the Ford Foundation in 1969 enabled it to boost its secretariat and expand
operations. During the 1960s, IUCN lobbied the UN General Assembly to create a new status for NGOs.
Resolution 1296, adopted in 1968, granted 'consultative' status to NGOs. IUCN itself was eventually
accredited with six UN organizations.[10] IUCN was one the few NGOs formally involved in the preparations
of the United Nations Conference on the Human Environment (Stockholm, 1972). The Stockholm
Conference eventually led to three new international conventions, with IUCN involved in their drafting and
implementation:
 Convention Concerning the Protection of World Cultural and Natural

Heritage (1972). IUCN provides technical evaluations and monitoring
 CITES- the Convention on International Trade in Endangered Species
of Wild Fauna and Flora (1974) IUCN is a signatory party and the
CITES secretariat was originally lodged with IUCN
 Ramsar Convention – Convention on Wetlands of International
Importance (1975). The secretariat is still administered from IUCN's
headquarters.
IUCN entered into an agreement with the United Nations Environment Programme UNEP to provide
regular reviews of world conservation. The income this generated, combined with growing revenue via
WWF, put the organisation on relatively sound financial footing for the first time since 1948.
This period saw the beginning of a gradual change in IUCN’s approach to conservation. Ensuring the
survival of habitats and species remained its key objective, but there was a growing awareness that
economic and social demands had to be taken into account. IUCN started to publish guidelines on
sustainable development. In 1975 the IUCN General Assembly passed a resolution to retain indigenous
peoples and cater for their traditional rights in National Parks and protected areas. As a result, IUCN
became more appealing to organisations and governments in the developing world.
The World Conservation Strategy 1975–1985[11]
In the late seventies, between its General Assemblies in Kinshasha (1975) and Ashkabad (1978), IUCN
went through a phase of turbulence in governance and management. Its work program continued to grow,
in part as a result of the partnership with WWF. In 1978, IUCN was running 137 projects, largely in the
global south. The involvement of representatives from the developing world in the IUCN Council,
Committees and staff increased.
In 1975 IUCN started work on the World Conservation Strategy.
Stopping illegal trade of wildlife is one of IUCN's priorities
The drafting process – and the discussions with the UN agencies involved – led to an evolution in thinking
within IUCN and growing acceptance of the fact that conservation of nature by banning human presence no
longer worked. (The debate about the balance between strict nature protection and conservation through
sustainable development would, however, continue within IUCN well into the 1990s.) TheWorld
Conservation Strategy was launched in 35 countries simultaneously on 5 March 1980. It set out
fundamental principles and objectives for conservation worldwide, and identified priorities for national and
international action. It is considered one of the most influential documents in 20th century nature
conservation and one of the first official documents to introduce the concept of sustainable development.
The Strategy was followed in 1982 by the World Charter for Nature, which was adopted by the United
Nations General Assembly, after preparation by IUCN.
In 1980, IUCN and WWF moved into shared new offices in Gland, Switzerland. This marked a phase of
closer cooperation with WWF. It was the support of WWF that allowed IUCN to weather a financial crisis in
1980–1982. The close ties between IUCN and WWF were severed in 1985 when WWF decided to take
control of its own field projects, which so far had been run by IUCN. In 1989, IUCN moved into a separate
building in Gland, close to the offices it had shared with WWF.
Sustainable development and regionalisation: 1985–2000 [12]
In 1982, IUCN set up a Conservation for Development Centre within its secretariat. The Centre undertook
projects to ensure that nature conservation was integrated in development aid and in the economic policies
of developing countries. Over the years, it supported the development of national conservation strategies in
30 countries. Several European countries began to channel considerable amounts of bilateral aid via
IUCN’s projects. Management of these projects was primarily done by IUCN staff, often working from the
new regional and country offices IUCN set up around the world. This marked a shift within the organisation.
Previously the volunteer Commissions had been very influential, now the Secretariat and its staff began to
play a more dominant role. Initially, the focus of power was still with the Headquarters in Gland but the
regional offices and regional members’ groups gradually got a bigger say in operations.
In spite of the increased attention for sustainable development, the protection of habitats and species
remained a core activity of IUCN. Special programs were developed for Antarctica, tropical forests and
wetlands, and IUCN expanded its operations in Latin America.
In 1991, IUCN (together with UNEP and WWF) published Caring for the Earth, a successor to the World
Conservation Strategy. It was published in the run-up to the Earth Summit, the 1992 UN Conference on
Environment and Development in Rio de Janeiro. The World Conservation Strategy, Caring for the Earth,
and the Global Diversity Strategy (also published in 1992 by UNEP, IUCN, and WRI) are considered hugely
influential in shaping the global environmental agenda. They lay the foundations for the Convention on
Biological Diversity, a new global treaty for the conservation and sustainable use of biological diversity
developed by UNEP with support from IUCN, the Framework Convention on Climate Change and Agenda
21.[10]
Social aspects of conservation were now integrated in IUCN’s work; projects began to take account of the
role of women in natural resource management and to value the knowledge indigenous peoples have
about their natural environment. At the General Assembly in 1994 the IUCN mission was redrafted to its
current wording to include the equitable and ecologically use of natural resources.
IUCN-Headquarters in Gland, Switzerland
Closer to business: 2000 to present day

The increased attention on sustainable development as a means to protect nature brought IUCN closer to
the corporate sector. A discussion started about cooperation with business, including the question if
commercial companies could become IUCN members. The members decided against this, but IUCN did
forge a partnership with the World Business Council for Sustainable Development.
The IUCN Global Business and Biodiversity Program (BBP) was established in 2003. The Program wants
to engage with business sectors that have a significant impact on natural resources and livelihoods to
promote sustainable use of natural resources.[13] Most prominent in the Business and Biodiversity Program
is the five-year collaboration IUCN started with the energy company Shell International in 2007. The aim
was to mitigate the environmental impact of Shell's operations. The partnership almost immediately came
under fire from IUCN's members, especially the NGO-members who feared for IUCN’s reputation. At the
World Conservation Congress (formerly the IUCN General Assembly) in Barcelona in 2008 NGO-members
tabled a motion to terminate the Shell contract. The proposal was narrowly defeated. [14][15]
Timeline[edit]
Some key dates in the growth and development of IUCN:
 1948: International Union for the Preservation of Nature (IUPN) established  1980: IUCN (toge
 1956: Name changed to the International Union for the Conservation of Nature and Natural the World Wide Fund
Resources (IUCN) Conservation Strategy
 1959: UNESCO decides to create an international list of Nature Parks and equivalent reserves, and  1982: Following I
the United Nations Secretary General asks the IUCN to prepare this list Assembly adopts the W
 1961: The World Wildlife Fund set up as a complimentary organisation to focus on fund raising,  1990: Began using
public relations, and increasing public support for nature conservation while continuing using
 1969: IUCN obtains a grant from the Ford Foundation which enables it to boost its international  1991: IUCN (toge
secretariat. theWorld Wide Fund f
 1972: UNESCO adopts the Convention Concerning the Protection of World Cultural and Natural  2001: Establishme
Heritage and the IUCN is invited to provide technical evaluations and monitoring  2008: Stopped usi
 1974: IUCN is involved in obtaining the agreement of its members to sign a Convention on its name back to Intern
International Trade in Endangered Species of Wild Fauna and Flora (CITES), whose secretariat was  2012: IUCN publi
originally lodged with the IUCN
 1975: The Convention on Wetlands of International Importance (Ramsar Convention) comes into
force, and its secretariat is administered from the IUCN's headquarters
Current work[edit]
Workprogram 2013–2016[edit]
According to its website, IUCN works on the following topics: business,
economics, ecosystems, education, environmental law, forest conservation, gender, global
policy, marineand polar, protected areas, science and knowledge, social policy, species, wildlife trade,
water and world heritage.[16]
IUCN works on the basis of four-year programs, determined by the membership. In the IUCN Program for
2013–2016 conserving nature and biodiversity is inextricably linked to sustainable development and
poverty reduction. IUCN states that it aims to have a solid factual base for its work and takes into account
the knowledge held by indigenous groups and other traditional users of natural resources.
The 2013–2016 work program identifies three program areas:
1. Valuing and conserving nature.

2. Effective and equitable governance of nature’s use.
3. Deploying nature-based solutions to global challenges in climate,
food and development.[17]
Unlike other environmental NGOs, IUCN does not itself aim to directly mobilize the general public.
Education has been part of IUCN's work program since the early days but the focus is on stakeholder
involvement and strategic communication rather than mass-campaigns. [18]
Habitats and species[edit]

IUCN runs field projects for habitat and species conservation around the world. It produces the IUCN Red
List of Threatened Species and the IUCN Red List of Ecosystems which in a similar way measures risks to
ecosystems. The IUCN Red List of Ecosystems is a global standard to assess the conservation status of
ecosystems. It is applicable at local, national, regional and global levels. It is based on a set of rules, or
criteria, for performing evidence-based, scientific assessments of the risk of ecosystem collapse, as
measured by reductions in geographical distribution or degradation of the key processes and components
of ecosystems.
IUCN participates in efforts to restore critically endangered species. In 2012 it published a list of the world's
100 most threatened species. It wants to expand the global network ofnational parks and other protected
areas and promote good management of such areas, for example through the publication of the Green List
of well-managed protected areas.[19] IUCN is the governing body responsible for the development of
the Protected Area Management Categories into which each protected area is divided depending on its
conservation requirements and management aims. It is also developing a standard to identify Key
Biodiversity Areas — places of international importance for conservation. In particular, it focuses on greater
protection of the oceans and marine habitats.
Mongolian Przewalski Horse

Arabian oryx
California Condor
Oceans
Antarctica
Mangrove forest
Examples of endangered species and threatened habitats that are the focus of IUCN programs
Business partnerships[edit]
IUCN has a growing program of partnerships with the corporate sector to promote sustainable use of
natural resources. In its Annual Report over 2013 IUCN list cooperation withGlobal Blue, Groupe
Danone, Holcim, Nokia Corporation, Rio Tinto Group, Sakhalin Energy Investment Company Limited, Shell
Nigeria, Marriott International and Nespresso.[20]
National and international policy[edit]

On the national level, IUCN helps governments prepare national biodiversity policies. Internationally, IUCN
provides advice to environmental conventions such as the Convention on Biological Diversity, CITES and
the Framework Convention on Climate Change. It advises UNESCO on natural world heritage.
It has a formally accredited permanent observer mission to the United Nations in New York. According to
its own website, IUCN is the only international observer organization in the UN General Assembly with
expertise in issues concerning the environment, specifically biodiversity, nature conservation and
sustainable natural resource use.[21]
IUCN has official relations with the Council of Europe, the Food and Agriculture Organization of the United
Nations (FAO), the International Maritime Organization (IMO), theOrganization of American States (OAS),
the United Nations Conference on Trade and Development (UNCTAD), the United Nations Environment
Programme (UNEP), the UNEP World Conservation Monitoring Centre (UNEP-WCMC), the United Nations
Educational, Scientific and Cultural Organization (UNESCO), the World Intellectual Property
Organization(WIPO) and the World Meteorological Organization (WMO).[22]
Organizational structure[edit]
As an organization, IUCN has three components: the member organizations, the six scientific commissions,
and the secretariat.
Members[edit]
IUCN members are states, government agencies, international nongovernmental organizations, national
nongovernmental organizations or other affiliates. In 2014, IUCN had 1218 members. The members can
organize themselves in national or regional committees to promote cooperation. In 2014, there were 56
national committees and 7 regional committees.
Stamp commemorating the 1978 IUCN General Assembly inAshgabat
Commissions[edit]
The six IUCN Commissions involve 10,000 volunteer experts from a range of disciplines. They 'assess the
state of the world’s natural resources and provide the Union with sound know-how and policy advice on
conservation issues'.[23]
 Commission on Education and Communication (CEC): communication,

learning and knowledge management in IUCN and the wider
conservation community. Members: 1,200
 Commission on Environmental, Economic, and Social Policy (CEESP):
economic and social factors for the conservation and sustainable use
of biological diversity. Members: 1465.
 World Commission on Environmental Law (WCEL): developing new
legal concepts and instruments, and building the capacity of societies
to employ environmental law for conservation and sustainable
development. Members: 800.
 Commission on Ecosystem Management(CEM): integrated ecosystem
approaches to the management of natural and modified ecosystems.
Members: 1000.
 Species Survival Commission (SSC): technical aspects of species
conservation and action for species that are threatened with extinction.
Members: 7500.
Main article: IUCN Species Survival Commission
 World Commission on Protected Areas (WCPA): establishment and

effective management of a network of terrestrial and marine protected
areas. Members: 1300.
Main article: World Commission on Protected Areas
Secretariat[edit]
The Secretariat is led by the Director General. For management of its operations IUCN distinguishes eight
geographical regions; each is led by a director who reports to the Director General.
The IUCN head office is in Gland, Switzerland. Eight regional offices implement IUCN’s program in their
respective territories. Since 1980, IUCN has established offices in more than 45 countries. The total
number of staff grew from 100 (1980) to around 1,000 (2014); nearly all this growth was in the national and
regional offices. Approximately 150 staff are based in the head office. [24]
Governance and funding[edit]

Governance[edit]
Inger Andersen, IUCN Director General since January 2015
The World Conservation Congress (Members’ Assembly) is IUCN’s highest decision-making body. The

Congress convenes every four years, most recently in Hawaii (2016) and previously in Jeju, South Korea
(2012). It elects the Council, including the President, and approves IUCN’s workprogram and budget.
The IUCN Council is the principal governing body of IUCN. The Council provides strategic direction for the
activities of the Union, discusses specific policy issues and provides guidance on finance and the
membership development of the Union. The Council is composed of the President, four Vice Presidents
(elected by the Council from among its members), the Treasurer, the Chairs of IUCN's six Commissions,
three Regional Councillors from each of IUCN's eight Statutory Regions and a Councillor from the State in
which IUCN has its seat (Switzerland). IUCN's current President is Zhang Xinsheng.
The Council appoints a Director General, who is responsible for the overall management of IUCN and the
running of the Secretariat.Inger Andersen is IUCN Director General since January 2015.[25] She
succeeded Julia Marton-Lefèvre.[26]
IUCN Presidents since 1948[27] IUCN Directors General since 1948[27]
 1948–1954: Charles Jean Bernard  1948–1955: Jean Paul Harro

 1954–1958: Roger Heim  1959–1960: M.C. Bloemers
 1958–1963: Jean Georges Baer  1962: Gerald Watterson

 1963–1966: Hugh Elliott
 1963–1966: François Bourlière
 1966–1970: Joe Berwick
 1966–1972: Harold J. Coolidge
 1970–1976: Gerardo Budow
 1972–1978: Donald Kuenen  1977–1980: David Munro
 1978–1984: Mohamed Kassas  1980–1982: Lee M. Talbot

 1983–1988: Kenton Miller
 1984–1990: M. S. Swaminathan
 1988–1994: Martin Holdgate
 1990–1994: Sridath Ramphal
 1994–1999: David McDowe
 1994–1996: Jay D. Hair
 1999–2001: Marita Koch-We
 1996–2004: Yolanda Kakabadse
 2001–2006: Achim Stei
 2004–2008: Valli Moosa
 2007–2014: Julia Marton-Le
 2008–2012: Ashok Khosla
 since 2015: Inger Andersen
 Since 2012: Zhang Xinsheng
Funding[edit]
IUCN’s total income in 2013 was 114 million CHF, equaling approximately 95 million Euro or 116 million US
dollar.
IUCN’s funding mainly comes from Official Development Assistance budgets of national, international or
intergovernmental institutions. This represented 61% of its income in 2013. Additional sources of income
are the membership fees, as well as grants and project funding from foundations, institutions and
corporations.[28]
Influence and criticism[edit]

Influence[edit]
IUCN is considered one of the most influential conservation organisations in the world and, together with
WWF and the World Resources Institute (WRI), is seen as a driving force behind the rise of NGO influence
at the UN and around the world.[29][30]
It has established a network covering all aspects of global conservation via its worldwide membership of
governmental and non-governmental organisations, the participation of experts in the IUCN commissions,
formal involvement in international agreements, ties to intergovernmental organisations and increasingly
partnerships with international business. The World Conservation Congress and the World Parks event
organised by IUCN are the largest gatherings of organisations and individuals involved in conservation
worldwide. They involve governmental organisations, NGOs, media, academia and the corporate sector.
According to some, IUCN is not only a major global player in conservation action, but also has considerable
influence in defining what nature conservation actually is.[31] The IUCN Red List of Threatened Species and
the IUCN Red List of Ecosystems determine which species and natural areas merit protection. Through the
Green List of well-managed protected areas and the system of IUCN protected area categories IUCN
influences how protected areas are managed.
Criticism[edit]
The relevance of the scientific insights and the data that IUCN produces are not often drawn into question,
but IUCN has encountered criticism throughout its history. Its actions can still lead to controversy.
It has been claimed that IUCN put the needs of nature above those of humans, disregarding economic
considerations and the interests of indigenous peoples and other traditional users of the land. Until the
1980s IUCN favored the "Yellowstone Model’ of conservation which called for the removal of humans from
protected areas. The expulsion of the Maasai people from Serengeti National Park and the Ngorongoro
Conservation Area is perhaps the best known example of this approach.[3][8]
IUCN's relationships with local land users like the Maasai have caused controversy in the past
This is linked to another criticism that has been directed at IUCN, namely that throughout its history it has
mainly been ‘Northern focused’, i.e. had a West-European or North-American perspective on global
conservation. Some critics point to the fact that many individuals involved in the establishment of IUCN had
been leading figures in the British Society for the Preservation of the Wild Fauna of Empire, which wanted
to protect species against the impact of ‘native’ hunting pressure in order to safeguard hunting by
Europeans.[31] The fact that at least until the 1990s, most of IUCN staff, the chairs of the Commissions and
the IUCN President came from western countries has also led to criticism. [12] Over the past decade, IUCN
has changed its approach. It now aims to work in close cooperation with indigenous groups. It has also
become more regionalized in its operations and more truly global in its staffing. [12]
More recently, activist environmental groups have argued that IUCN is too closely associated with
governmental organisations and with the commercial sector. [30] IUCN’s cooperation with Shell came in for
criticism, also from its own membership.[15] Its decision to hold the 2012 World Conservation Congress
on Jeju Island, South Korea, where the local community and international environmental activists were
protesting against the construction of a navy base also led to controversy. [32] IUCN remains committed to its
partnerships with the business sector, seeing sustainable development as the way to ensure long-term
protection of natural areas and species.[33]
Publications[edit]
IUCN has a wide range of publications, reports, guidelines and databases related to conservation
and sustainable development. It publishes or co-authors more than 150 books and major assessments
every year, along with hundreds of reports, documents and guidelines. [34] Since 2006, every year around 40
scientific papers listing "IUCN" as an author’s affiliation have been published in the peer-reviewed literature
indexed in the Web of Science. This is a tenfold increase since the 1980s.[35]
A report, released at the IUCN World Parks Congress in Sydney on 13 November 2014 showed that the
209,000 conservation reserves around the world now cover 15.4 per cent of the total land area. The new
figures are a step in the right direction of protecting 17 percent of land and 10 percent of ocean
environments on Earth by 2020 since an agreement between the worlds nations at the Convention on
Biological Diversity, held in Japan in 2010.[36]
At its World Conservation Congress in Hawaii in 2016, the IUCN launched a report Explaining ocean
warming: causes, scale, effects and consequences, one of the most comprehensive reviews to date on
ocean warming.[37]
See also[edit]
 List of conservation organisations
 List of environmental organizations
Footnotes[edit]
1. Jump up^ The information in the section on history is largely based
on Holdgate, M. 1999. The green web: a union for world conservation.
Earthscan. For each paragraph in the section one reference to the
pages used is included following the header. Where information in the
paragraph is based on other sources a separate reference is included
in the text
References[edit]
1. Jump up^ "About IUCN:IUCN's Vision and Mission". iucn.org. IUCN.
Retrieved 27 November2015.
2. ^ Jump up to: "About IUCN". IUCN. Retrieved 17 November 2014.
a b
3. ^ Jump up to: "Kenya: The Maasai Stand up to IUCN Displacement

a b c
Attempts from their Forest". World Rainforest Movement. Retrieved 2

December 2014.
4. Jump up^ < "Environmentalists Spar Over Corporate
Ties". Worldwatch. Retrieved 5 December2014.
5. Jump up^ Holdgate, Martin. The green web: a union for world
conservation. Earthscan. pp. 16–38.ISBN 1 85383 595 1.
6. Jump up^ (French) "Les 10 succès de Pro Natura", Pro Natura (page
visited on 26 July 2016).
conservation. Earthscan. pp. 47–63.ISBN 1 85383 595 1.
8. ^ Jump up to: Holdgate, Martin. The green web: a union for world
a b
conservation. Earthscan. pp. 67–82. ISBN 1 85383 595 1.

10. ^ Jump up to: "Understanding
a b
NGOs". agendatwentyone.wordpress.com. WordPress.com.

Retrieved 5 December 2014.
12. ^ Jump up to: Holdgate, Martin. The green web: a union for world
a b c

13. Jump up^ "Global Business and Biodiversity Programme". IUCN.
Retrieved 28 November 2014.
14. Jump up^ "IUCN and Shell: Guiding the way". Business &
Biodiversity. Retrieved 5 December2014.
15. ^ Jump up to: "Environmentalists spar over corporate ties". Worldwatch.
a b
Retrieved 5 December2014.
16. Jump up^ "What we do". IUCN. Retrieved 4 December 2014.
17. Jump up^ "IUCN Global Program". IUCN. Retrieved 4
December 2014.
18. Jump up^ "CEC – what we do". IUCN. Retrieved 26
December 2014.
19. Jump up^ "'Green List' awards world's top conservation
sites". Australian Geographic. 14 November 2014. Retrieved 18
November 2014.
20. Jump up^ "IUCN Annual Report 2013" (PDF). IUCN. pp. 16–17.
21. Jump up^ "About IUCN: secretariat and offices". IUCN. Retrieved 4
December 2014.
22. Jump up^ "UNESCO NGO database". UNESCO. Retrieved 4
December 2014.
23. Jump up^ "IUCN – Commissions". International Union for
Conservation of Nature. 12 May 2010. Retrieved 8 September 2010.
24. Jump up^ "About IUCN". IUCN. Retrieved 22 December 2014.
25. Jump up^ "Inger Andersen named IUCN Director General". IUCN.
26. Jump up^ "Our Union". IUCN. Retrieved 3 December 2014.
27. ^ Jump up to: Hesselink, Frits; Čeřovský, Jan: Learning to Change the
a b
Future, IUCN 2008, p. 22. URL retrieved 2011-01-24.

28. Jump up^ "IUCN Annual Report 2013" (PDF). IUCN. Retrieved 22
December 2014.
29. Jump up^ "Understanding NGOs". AgendaTwentyone. Retrieved 5
December 2014.
30. ^ Jump up to: "What is IUCN?". WiseGeek. Retrieved 12
a b
December 2014.
31. ^ Jump up to: MacDonald, Kenneth. IUCN: A History of Constraint (PDF).
a b
UCLouvain. Retrieved12 December 2014.

32. Jump up^ "Jeju island navy base controversy divides
iucn". Biodiversity media alliance. Retrieved 12 December 2014.
33. Jump up^ "Natural capital must be the way forward, says IUCN
director general". The Guardian. Retrieved 21 January 2015.
34. Jump up^ "Publications". IUCN. Retrieved 2012-01-28.
35. Jump up^ IUCN Annual Report
2013 (PDF).https://portals.iucn.org/library/sites/library/files/documents/I
UCN-2014-017.pdf: IUCN. p. 7.
36. Jump up^ "Big increase in Earth's protected areas". Australian
Geographic. 13 November 2014. Retrieved 17 November 2014.
37. Jump up^ Baxter, J.M.; Laffoley, Daniel D'A (September 5,
2016). "Explaining ocean warming". IUCN. Retrieved September
9, 2016.
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Down syndrome
Down syndrome
Down's syndrome
A boy with Down syndrome assembling a bookcase
Classification and external resources
Specialty Medical genetics, pediatrics
ICD-10 Q90
ICD-9-CM 758.0
OMIM 190685
DiseasesDB 3898
MedlinePlus 000997
eMedicine ped/615
Patient UK Down syndrome
MeSH D004314
[edit on Wikidata]
Down syndrome (DS or DNS), also known as trisomy 21, is a genetic disorder caused by the presence of
all, or part of a third copy of chromosome 21.[1] It is typically associated with physical growth delays,
characteristic facial features, and mild to moderateintellectual disability.[2] The average IQ of a young adult
with Down syndrome is 50, equivalent to the mental age of an 8- or 9-year-old child, but this can vary
widely.[3]
The parents of the affected individual are typically genetically normal.[4] The extra chromosome occurs by
random chance.[5] There is no known behavior or environmental factor that changes the risk. [5] Down
syndrome can be identified during pregnancy by prenatal screening followed by diagnostic testing, or after
birth by direct observation and genetic testing. [6] Since the introduction of screening, pregnancies with the
diagnosis are often terminated.[7][8] Regular screening for health problems common in Down syndrome is
recommended throughout the person's life. [3]
There is no cure for Down syndrome.[9] Education and proper care have been shown to improve quality of
life.[10] Some children with Down syndrome are educated in typical school classes, while others require more
specialized education.[11] Some individuals with Down syndrome graduate from high school and a few
attend post-secondary education.[12] In adulthood, about 20% in the United States do paid work in some
capacity[13] with many requiring a sheltered work environment. [11] Support in financial and legal matters is
often needed.[14] Life expectancy is around 50 to 60 years in the developed world with proper health care.[3][14]
Down syndrome is one of the most common chromosome abnormalities in humans.[3] It occurs in about one
per 1000 babies born each year.[2] In 2013, Down syndrome was present in 8.5 million individuals and
resulted in 36,000 deaths down from 43,000 deaths in 1990. [15][16] It is named after John Langdon Down, the
British doctor who fully described the syndrome in 1866. [17] Some aspects of the condition were described
earlier by Jean-Étienne Dominique Esquirol in 1838 and Édouard Séguin in 1844.[18] The genetic cause of
Down syndrome—an extra copy of chromosome 21—was identified by French researchers in 1959. [17]
Video explanation
Contents
[hide]
 1Signs and symptoms

o 1.1Physical
o 1.2Neurological
o 1.3Senses
o 1.4Heart
o 1.5Cancer
o 1.6Endocrine
o 1.7Gastrointestinal
o 1.8Teeth
o 1.9Fertility
 2Genetics
o 2.1Trisomy 21
o 2.2Translocation
 3Mechanism
o 3.1Epigenetics
 4Screening
o 4.1Ultrasound
o 4.2Blood tests
 5Diagnosis
o 5.1Before birth
o 5.2Abortion rates
o 5.3After birth
 6Management
o 6.1Health screening
o 6.2Cognitive development
o 6.3Other
 7Prognosis
 8Epidemiology
 9History
 10Society and culture
o 10.1Name
o 10.2Ethics
o 10.3Advocacy groups
 11Research
 12References
Signs and symptoms
A drawing of the facial features of an infant with Down syndrome

An eight-year-old boy with Down syndrome
Those with Down syndrome nearly always have physical and intellectual disabilities. [19] As adults, their
mental abilities are typically similar to those of an 8- or 9-year-old. [3] They also typically have poor immune
function[4] and generally reachdevelopmental milestones at a later age.[14] They have an increased risk of a
number of other health problems, includingcongenital heart defect, epilepsy, leukemia, thyroid diseases,
and mental disorders, among others.[17]
Percentag
Characteristics Characteristics Percentage
e
Mental impairment 99%[20] Abnormal teeth 60%[21]
Stunted growth 90%[22] Slanted eyes 60%[4]
Umbilical hernia 90%[23] Shortened hands 60%[21]
Increased skin back of neck 80%[17] Short neck 60%[21]
Low muscle tone 80%[24] Obstructive sleep apnea 60%[17]
Narrow roof of mouth 76%[21] Bent fifth finger tip 57%[4]

Flat head 75%[4] Brushfield spots in the iris 56%[4]
Flexible ligaments 75%[4] Single transverse palmar crease 53%[4]
Proportionally large tongue[25] 75%[24] Protruding tongue 47%[21]
Abnormal outer ears 70%[17] Congenital heart disease 40%[21]
Flattened nose 68%[4] Strabismus ~35%[2]
Separation of first and second

68%[21] Undescended testicles 20%[26]
toes
Physical
Feet of a boy with Down syndrome
People with Down syndrome may have some or all of these physical characteristics: a small chin, slanted
eyes, poor muscle tone, a flat nasal bridge, a single crease of the palm, and a protruding tongue due to a
small mouth and relatively large tongue.[24][25] These airway changes lead to obstructive sleep apnea in
around half of those with Down syndrome.[17] Other common features include: a flat and wide face,[24] a short
neck, excessive joint flexibility, extra space between big toe and second toe, abnormal patterns on the
fingertips and short fingers.[21][24] Instability of the atlantoaxial joint occurs in about 20% and may lead
to spinal cord injury in 1–2%.[3][14] Hip dislocations may occur without trauma in up to a third of people with
Down syndrome.[17]
Growth in height is slower, resulting in adults who tend to have short stature—the average height for men is
154 cm (5 ft 1 in) and for women is 142 cm (4 ft 8 in).[27] Individuals with Down syndrome are at increased
risk for obesity as they age.[17]Growth charts have been developed specifically for children with Down
syndrome.[17]
Neurological
Most individuals with Down syndrome have mild (IQ: 50–69) or moderate (IQ: 35–50) intellectual
disability with some cases having severe (IQ: 20–35) difficulties.[2][28] Those with mosaic Down syndrome
typically have IQ scores 10–30 points higher.[29] As they age, people with Down syndrome typically perform
less well than their same-age peers.[28][30] Some after 30 years of age may lose their ability to speak.[3] This
syndrome causes about a third of cases of intellectual disability. [4]Many developmental milestones are
delayed with the ability to crawl typically occurring around 8 months rather than 5 months and the ability to
walk independently typically occurring around 21 months rather than 14 months.[31]
Commonly, individuals with Down syndrome have better language understanding than ability to speak. [17]
[28]
Between 10 and 45% have either a stutter or rapid and irregular speech, making it difficult to understand
them.[32] They typically do fairly well with social skills.[17] Behavior problems are not generally as great an
issue as in other syndromes associated with intellectual disability. [28] In children with Down
syndrome, mental illness occurs in nearly 30% with autism occurring in 5–10%.[14] People with Down
syndrome experience a wide range of emotions.[33] While people with Down syndrome are generally happy,
[34]
symptoms of depression and anxiety may develop in early adulthood.[3]
Children and adults with Down syndrome are at increased risk of epileptic seizures which occur in 5–10%
of children and up to 50% of adults.[3] This includes an increased risk of a specific type of seizure
called infantile spasms.[17] Many (15%) who live 40 years or longer develop Alzheimer disease.[35] In those
who reach 60 years of age, 50–70% have the disease. [3]
Senses
Brushfield spots, visible in the irises of a baby with Down syndrome
Hearing and vision disorders occur in more than half of people with Down syndrome. [17] Vision problems
occur in 38 to 80%.[2] Between 20 and 50% have strabismus, in which the two eyes do not move together.
[2]
Cataracts (cloudiness of the lens of the eye) occur in 15%, [14] and may be present at birth.
[2]
Keratoconus (a thin, cone-shaped cornea)[3] andglaucoma (increased eye pressure) are also more
common,[2] as are refractive errors requiring glasses or contacts.[3]Brushfield spots (small white or
grayish/brown spots on the outer part of the iris) are present in 38 to 85% of individuals. [2]
Hearing problems are found in 50–90% of children with Down syndrome. [36] This is often the result of otitis
media with effusion which occurs in 50–70%[14] and chronic ear infections which occur in 40 to 60%.[37] Ear
infections often begin in the first year of life and are partly due to poor eustachian tube function.[38]
[39]
Excessive ear wax can also cause hearing loss due to obstruction of the outer ear canal. [3] Even a mild
degree of hearing loss can have negative consequences for speech, language understanding, and
academics.[2][39]Additionally, it is important to rule out hearing loss as a factor in social and cognitive
deterioration.[40] Age-related hearing loss of the sensorineural type occurs at a much earlier age and affects
10–70% of people with Down syndrome.[3]
Heart
The rate of congenital heart disease in newborns with Down syndrome is around 40%.[21] Of those with
heart disease, about 80% have an atrioventricular septal defect orventricular septal defect with the former
being more common.[3] Mitral valve problems become common as people age, even in those without heart
problems at birth.[3] Other problems that may occur include tetralogy of Fallot and patent ductus arteriosus.
[38]
People with Down syndrome have a lower risk of hardening of the arteries.[3]
Cancer
Although the overall risk of cancer is not changed,[41] the risk of leukemia and testicular cancer is increased
and risk of solid cancers is reduced. [3] Solid cancers are believed to be less common due to increased
expression of tumor suppressor genes present on chromosome 21.[42]
Cancers of the blood are 10 to 15 times more common in children with Down syndrome.[17] In
particular, acute lymphoblastic leukemia is 20 times more common and themegakaryoblastic form of acute
myeloid leukemia is 500 times more common.[43] Transient myeloproliferative disease, a disorder of blood
cell production that does not occur outside of Down syndrome, affects 3–10% of infants. [43][44] The disorder is
typically not serious but occasionally can be. [44] It resolves most times without treatment; however, in those
who have had it, a 20 to 30% risk of developing acute lymphoblastic leukemia at a later time exists. [44]
Endocrine
Problems of the thyroid gland occur in 20–50% of individuals with Down syndrome. [3][17] Low thyroid is the
most common form, occurring in almost half of all individuals. [3] Thyroid problems can be due to a poorly or
nonfunctioning thyroid at birth (known as congenital hypothyroidism) which occurs in 1%[14] or can develop
later due to an attack on the thyroid by the immune system resulting in Graves' disease or autoimmune
hypothyroidism.[45] Type 1 diabetes mellitus is also more common.[3]
Gastrointestinal
Constipation occurs in nearly half of people with Down syndrome and may result in changes in behavior.
[17]
One potential cause is Hirschsprung's disease, occurring in 2–15%, which is due to a lack of nerve cells
controlling the colon.[46] Other frequent congenital problems include duodenal atresia, pyloric
stenosis, Meckel diverticulum, and imperforate anus.[38] Celiac disease affects about 7–20%[3]
[17]
and gastroesophageal reflux disease is also more common.[38]
Teeth
Individuals with Down syndrome tend to be more susceptible to gingivitis as well as early,
severe periodontal disease, necrotising ulcerative gingivitis, and early tooth loss, especially in the lower
front teeth.[47][48] While plaque and poor oral hygiene are contributing factors, the severity of these
periodontal disease cannot be explained solely by external factors. [48] Research suggests that the severity is
likely a result of a weakened immune system.[48][49] The weakened immune system also contributes to
increased incidence of yeast infections in the mouth (from Candida albicans).[49]
Individuals with Down syndrome also tend to have a more alkaline saliva resulting in a greater resistance
to tooth decay, despite decreased quantities of saliva,[50] less effective oral hygiene habits and higher
plaque indexes.[47][49][50][51]
Higher rates of tooth wear and bruxism are also common.[49] Other common oral manifestations of Down
syndrome include enlarged hypotonic tongue, crusted and hypotonic lips, mouth breathing, narrow palate
with crowded teeth, class III malocclusion with an underdeveloped maxilla and posterior crossbite, delayed
exfoliation of baby teeth and delayed eruption of adult teeth, shorter roots on teeth, and often missing and
malformed (usually smaller) teeth.[47][49][50][51] Less common manifestations include cleft lip and palate,enamel
hypocalcification (20% prevalence).[51]
Fertility
Males with Down syndrome usually do not father children, while females have lower rates of fertility relative
to those who are unaffected.[52] Fertility is estimated to be present in 30–50% of females.
[53]
Menopause typically occurs at an earlier age.[3] The poor fertility in males is thought to be due to
problems with sperm development; however, it may also be related to not being sexually active. [52] As of
2006, three instances of males with Down syndrome fathering children and 26 cases of females having
children have been reported.[52] Without assisted reproductive technologies, around half of the children of
someone with Down syndrome will also have the syndrome.[52][54]
Genetics
Main article: Genetics of Down syndrome
Karyotype for trisomy Down syndrome: Notice the three copies of chromosome 21
Down syndrome is caused by having three copies of the genes on chromosome 21, rather than the usual
two.[1][55] The parents of the affected individual are typically genetically normal. [4] Those who have one child
with Down syndrome have about a 1% risk of having a second child with the syndrome, if both parents are
found to have normal karyotypes.[53]
The extra chromosome content can arise through several different ways. The most common cause (about
92–95% of cases) is a complete extra copy of chromosome 21, resulting in trisomy 21.[54][56] In 1.0 to 2.5% of
cases, some of the cells in the body are normal and others have trisomy 21, known as mosaic Down
syndrome.[53][57] The other common mechanisms that can give rise to Down syndrome include:
a Robertsonian translocation, isochromosome, or ring chromosome. These contain additional material from
chromosome 21 and occur in about 2.5% of cases.[17][53] An isochromosome results when the two long arms
of a chromosome separate together rather than the long and short arm separating together during egg or
sperm development.[54]
Trisomy 21
Trisomy 21 (also known by the karyotype 47,XX,+21 for females and 47,XY,+21 for males)[58] is caused by a
failure of the 21st chromosome to separate during egg or sperm development. [54] As a result, a sperm or
egg cell is produced with an extra copy of chromosome 21; this cell thus has 24 chromosomes. When
combined with a normal cell from the other parent, the baby has 47 chromosomes, with three copies of
chromosome 21.[1][54] About 88% of cases of trisomy 21 result from nonseparation of the chromosomes in
the mother, 8% from nonseparation in the father, and 3% after the egg and sperm have merged. [59]
Translocation
The extra chromosome 21 material may also occur due to a Robertsonian translocation in 2–4% cases.[53]
[60]
In this situation, the long arm of chromosome 21 is attached to another chromosome, often chromosome
14.[61] In a male affected with Down syndrome, it results in a karyotype of 46XY,t(14q21q). [61][62] This may be a
new mutation or previously present in one of the parents. [63] The parent with such a translocation is usually
normal physically and mentally;[61] however, during production of egg or sperm cells, a higher chance of
creating reproductive cells with extra chromosome 21 material exists. [60] This results in a 15% chance of
having a child with Down syndrome when the mother is affected and a less than 5% probability if the father
is affected.[63] The probability of this type of Down syndrome is not related to the mother's age. [61] Some
children without Down syndrome may inherit the translocation and have a higher probability of having
children of their own with Down syndrome.[61] In this case it is sometimes known as familial Down syndrome.
[64]
Mechanism
The extra genetic material present in DS results in overexpression of a portion of the 310 genes located on
chromosome 21.[55] This overexpression has been estimated at around 50%. [53] Some research has
suggested the Down syndrome critical region is located at bands 21q22.1–q22.3, [65] with this area including
genes for amyloid, superoxide dismutase, and likely the ETS2 proto oncogene.[66] Other research, however,
has not confirmed these findings.[55] microRNAs is also proposed to be involved.[67]
The dementia which occurs in Down syndrome is due to an excess of amyloid beta peptide produced in the
brain and is similar to Alzheimer's disease.[68] This peptide is processed from amyloid precursor protein, the
gene for which is located on chromosome 21.[68] Senile plaques and neurofibrillary tangles are present in
nearly all by 35 years of age, though dementia may not be present. [4] Those with DS also lack a normal
number of lymphocytes and produce less antibodies which contributes to their increased risk of infection. [17]
Epigenetics
Down syndrome is associated with an increased risk of many chronic diseases that are typically associated
with older age such as Alzheimer's disease. The accelerated aging suggest that trisomy 21 increases the
biological age of tissues, but molecular evidence for this hypothesis is sparse. According to a biomarker of
tissue age known as epigenetic clock, trisomy 21 increases the age of blood and brain tissue (on average
by 6.6 years).[69]
Screening
Guidelines recommend screening for Down syndrome to be offered to all pregnant women, regardless of
age.[70][71] A number of tests are used, with varying levels of accuracy. They are typically used in combination
to increase the detection rate.[17] None can be definitive, thus if screening is positive,
either amniocentesis or chorionic villous sampling is required to confirm the diagnosis.[70] Screening in both
the first and second trimesters is better than just screening in the first trimester. [70] The different screening
techniques in use are able to pick up 90 to 95% of cases with a false-positive rate of 2 to 5%. [72]
First- and second-trimester screening[70]
Week of
Detection False
Screen pregnancy when Description
rate positive
performed
Uses ultrasound to measure nuchal
Combined
10–13.5 wks 82–87% 5% translucency in addition to blood tests for free or
test
total beta-hCG and PAPP-A
Measures the maternal serum alpha-fetoprotein,

Quad screen 15–20 wks 81% 5%
unconjugated estriol, hCG, and inhibin-A
Integrated Is a combination of the quad screen, PAPP-A,

15–20 wks 94–96% 5%
test and NT
Cell-free A blood sample is taken from the mother

From 10 wks[73] 96-100%[74] 0.3%[75]
fetal DNA by venipuncture and is sent for DNA analysis.
Ultrasound
Ultrasound of fetus with Down syndrome showing alarge bladder
Enlarged NT and absent nasal bone in a fetus at 11 weeks with Down syndrome
Ultrasound imaging can be used to screen for Down syndrome. Findings that indicate increased risk when
seen at 14 to 24 weeks of gestation include a small or no nasal bone, large ventricles, nuchal fold
thickness, and an abnormal rightsubclavian artery, among others.[76] The presence or absence of many
markers is more accurate.[76] Increased fetal nuchal translucency (NT) indicates an increased risk of Down
syndrome picking up 75–80% of cases and being falsely positive in 6%. [77]
Blood tests
Several blood markers can be measured to predict the risk of Down syndrome during the first or second
trimester.[72][78]Testing in both trimesters is sometimes recommended and test results are often combined
with ultrasound results.[72] In the second trimester, often two or three tests are used in combination with two
or three of: α-fetoprotein, unconjugated estriol, total hCG, and free βhCG detecting about 60–70% of
cases.[78]
Testing of the mother's blood for fetal DNA is being studied and appears promising in the first trimester. [74]
[79]
The International Society for Prenatal Diagnosis considers it a reasonable screening option for those
women whose pregnancies are at a high risk for trisomy 21. [80] Accuracy has been reported at 98.6% in the
first trimester of pregnancy.[17] Confirmatory testing by invasive techniques (amniocentesis, CVS) is still
required to confirm the screening result.[80]
Diagnosis
Before birth
When screening tests predict a high risk of Down syndrome, a more invasive diagnostic test
(amniocentesis or chorionic villus sampling) is needed to confirm the diagnosis.[70] If Down syndrome occurs
in one in 500 pregnancies and the test used has a 5% false-positive rate, this means, of 26 women who
test positive on screening, only one will have Down syndrome confirmed. [72] If the screening test has a 2%
false-positive rate, this means one of eleven who test positive on screening have a fetus with DS.
[72]
Amniocentesis and chorionic villus sampling are more reliable tests, but they increase the risk
ofmiscarriage between 0.5 and 1%.[81] The risk of limb problems is increased in the offspring due to the
procedure.[81] The risk from the procedure is greater the earlier it is performed, thus amniocentesis is not
recommended before 15 weeks gestational age and chorionic villus sampling before 10 weeks gestational
age.[81]
Abortion rates
About 92% of pregnancies in Europe with a diagnosis of Down syndrome are terminated. [8] In the United
States, termination rates are around 67%, but this rate varied from 61% to 93% among different
populations evaluated.[7] When nonpregnant people are asked if they would have a termination if their fetus
tested positive, 23–33% said yes, when high-risk pregnant women were asked, 46–86% said yes, and
when women who screened positive are asked, 89–97% say yes. [82]
After birth
The diagnosis can often be suspected based on the child's physical appearance at birth. [14] An analysis of
the child's chromosomes is needed to confirm the diagnosis, and to determine if a translocation is present,
as this may help determine the risk of the child's parents having further children with Down syndrome.
[14]
Parents generally wish to know the possible diagnosis once it is suspected and do not wish pity. [17] The
National Down Syndrome Society have developed information regarding the positive aspects of life with
Down Syndrome.[83]
Management
Efforts such as early childhood intervention, screening for common problems, medical treatment where
indicated, a good family environment, and work-related training can improve the development of children
with Down syndrome. Education and proper care can improve quality of life.[10] Raising a child with Down
syndrome is more work for parents than raising an unaffected child. [84] Typical childhood vaccinations are
recommended.[17]
Health screening
Recommended screening
Testing Children[85] Adults[3]
Hearing 6 months, 12 months, then yearly 3–5 years
T4 and TSH 6 months, then yearly
Eyes 6 months, then yearly 3–5 years
Teeth 2 years, then every 6 months
Coeliac Between 2 and 3 years of age,

disease or earlier if symptoms occur
3 to 4 years, or earlier if
Sleep study symptoms
of obstructive sleep apnea occur
Neck X-rays Between 3 and 5 years of age
A number of health organizations have issued recommendations for screening those with Down syndrome
for particular diseases.[85] This is recommended to be done systematically.[17]
At birth, all children should get an electrocardiogram and ultrasound of the heart.[17] Surgical repair of heart
problems may be required as early as three months of age. [17] Heart valve problems may occur in young
adults, and further ultrasound evaluation may be needed in adolescents and in early adulthood. [17] Due to
the elevated risk of testicular cancer, some recommend checking the person's testicles yearly. [3]
Cognitive development
Hearing aids or other amplification devices can be useful for language learning in those with hearing loss.
[17]
Speech therapy may be useful and is recommended to be started around 9 months of age. [17] As those
with Down's typically have good hand-eye coordination, learning sign language may be possible.
[28]
Augmentative and alternative communication methods, such as pointing, body language, objects, or
pictures, are often used to help with communication. [86] Behavioral issues and mental illness are typically
managed with counseling or medications.[14]
Education programs before reaching school age may be useful. [2] School-age children with Down syndrome
may benefit from inclusive education (whereby students of differing abilities are placed in classes with their
peers of the same age), provided some adjustments are made to the curriculum. [87] Evidence to support
this, however, is not very strong.[88] In the United States, the Individuals with Disabilities Education Act of
1975 requires public schools generally to allow attendance by students with Down's. [89]
Other
Tympanostomy tubes are often needed[17] and often more than one set during the person's childhood.
[36]
Tonsillectomy is also often done to help with sleep apnea and throat infections.[17] Surgery, however,
does not always address the sleep apnea and a continuous positive airway pressure (CPAP) machine may
be useful.[36] Physical therapy and participation in physical education may improve motor skills. [90] Evidence
to support this in adults, however, is not very good.[91]
Efforts to prevent respiratory syncytial virus (RSV) infection with human monoclonal antibodies should be
considered, especially in those with heart problems.[2] In those who develop dementia there is no evidence
for memantine,[92] donepezil,[93] rivastigmine,[94] or galantamine.[95]
Plastic surgery has been suggested as a method of improving the appearance and thus the acceptance of
people with Down's.[96] It has also been proposed as a way to improve speech.[96] Evidence, however, does
not support a meaningful difference in either of these outcomes. [96] Plastic surgery on children with Down
syndrome is uncommon,[97] and continues to be controversial.[96] The U.S. National Down Syndrome
Society views the goal as one of mutual respect and acceptance, not appearance. [97]
Many alternative medical techniques are used in Down syndrome; however, they are poorly supported by
evidence.[96] These include: dietary changes, massage, animal therapy,chiropractics and naturopathy,
among others.[96] Some proposed treatments may also be harmful.[53]
Prognosis
Deaths due to Downs syndrome per million persons in 2012
0-0
1-1
2-2
3-3
4-4
5-5
6-6
7-8
9-16
Between 5 and 15% of children with Down syndrome in Europe attend regular school. [98] Some graduate
from high school; however, most do not.[12] Of those with intellectual disability in the United States who
attended high school about 40% graduated. [99] Many learn to read and write and some are able to do paid
work.[12] In adulthood about 20% in the United States do paid work in some capacity. [13][100] In Europe,
however, less than 1% have regular jobs. [98] Many are able to live semi-independently,[4] but they often
require help with financial, medical, and legal matters. [14] Those with mosaic Down syndrome usually have
better outcomes.[53]
Individuals with Down syndrome have a higher risk of early death than the general population. [17] This is
most often from heart problems or infections.[2][3] Following improved medical care, particularly for heart
and gastrointestinal problems, the life expectancy has increased.[2] This increase has been from 12 years in
1912,[101] to 25 years in the 1980s,[2] to 50 to 60 years in the developed world in the 2000s.[3][14] Currently
between 4 and 12% die in the first year of life. [44] The probability of long-term survival is partly determined by
the presence of heart problems. In those with congenital heart problems 60% survive to 10 years and 50%
survive to 30 years of age.[4] In those without heart problems 85% survive to 10 years and 80% survive to
30 years of age.[4] About 10% live to 70 years of age.[54]
Epidemiology
The risk of having a Down syndrome pregnancy in relation to a mother's age[102]
Globally, as of 2010, Down syndrome occurs in about 1 per 1000 births [2] and results in about 17,000
deaths.[103] More children are born with Down syndrome in countries where abortion is not allowed and in
countries where pregnancy more commonly occurs at a later age. [2] About 1.4 per 1000 live births in the
United States[104] and 1.1 per 1000 live births in Norway are affected.[3] In the 1950s, in the United States, it
occurred in 2 per 1000 live births with the decrease since then due to prenatal screening and abortions.
[63]
The number of pregnancies with Down syndrome is more than two times greater with many
spontaneously aborting.[14] It is the cause of 8% of all congenital disorders.[2]
Maternal age affects the chances of having a pregnancy with Down syndrome. [102] At age 20, the chance is
one in 1441; at age 30, it is one in 959; at age 40, it is one in 84; and at age 50 it is one in 44. [102] Although
the probability increases with maternal age, 70% of children with Down syndrome are born to women 35
years of age and younger, because younger people have more children. [102] The father's older age is also a
risk factor in women older than 35, but not in women younger than 35, and may partly explain the increase
in risk as women age.[105]
History
It has been suggested that this Early Netherlandish painting depicts a person with Down syndrome as one of the angels.[106]
English physician John Langdon Down first characterized Down syndrome as a separate form of mental
disability in 1862, and in a more widely published report in 1866. [17][107][108] Édouard Séguin described it as
separate from cretinism in 1944.[18][109] By the 20th century, Down syndrome had become the most
recognizable form of mental disability.
In ancient times, many infants with disabilities were either killed or abandoned. [18] A number of historical
pieces of art are believed to portray Down syndrome, including pottery from AD 500 from South America
and the 16th-century painting The Adoration of the Christ Child.[18]
In the 20th century, many individuals with Down syndrome were institutionalized, few of the associated
medical problems were treated, and most died in infancy or early adult life. With the rise of the eugenics
movement, 33 of the then 48 U.S. states and several countries began programs of forced sterilization of
individuals with Down syndrome and comparable degrees of disability. Action T4 in Nazi Germany made
public policy of a program of systematic involuntary euthanization.[110]
With the discovery of karyotype techniques in the 1950s, it became possible to identify abnormalities of
chromosomal number or shape.[109] In 1959, Jérôme Lejeune reported the discovery that Down syndrome
resulted from an extra chromosome.[17] However, Lejeune's claim to the discovery has been disputed, [111] and
in 2014, the Scientific Council of the French Federation of Human Genetics unanimously awarded its
Grand Prize to his colleague Marthe Gautier for this discovery.[112] As a result of this discovery, the condition
became known as trisomy 21.[113] Even before the discovery of its cause, the presence of the syndrome in
all races, its association with older maternal age, and its rarity of recurrence had been noticed. Medical
texts had assumed it was caused by a combination of inheritable factors that had not been identified. Other
theories had focused on injuries sustained during birth. [114]
Society and culture

See also: List of people with Down syndrome
Name
Due to his perception that children with Down syndrome shared facial similarities with those
of Blumenbach's Mongolian race, John Langdon Down used the term 'mongoloid'. [54][115] While the term
mongoloid (also mongolism, Mongolian imbecility or idiocy) continued to be used until the early 1970s, it is
now considered unacceptable and is no longer in common use. [116] In 1961, 19 scientists suggested that
"mongolism" had "misleading connotations" and had become "an embarrassing term". [116][117] The World
Health Organization (WHO) dropped the term in 1965 after a request by the Mongolian delegate. [116]
In 1975, the United States National Institutes of Health (NIH) convened a conference to standardize the
naming and recommended eliminating the possessive form, Down's syndrome, [118] although both the
possessive and nonpossessive forms are used by the general population. [119] The term "trisomy 21" is also
used frequently.[117][120]
Ethics
Some argue that not to offer screening for Down syndrome is unethical. [121] As it is a medically reasonable
procedure, per informed consent, people should at least be given information about it.[121] It will then be the
woman's choice, based on her personal beliefs, how much or how little screening she wishes. [122][123] When
results from testing become available, it is also considered unethical not to give the results to the person in
question.[121][124]
Some deem it reasonable for parents to select a child who would have the highest well-being. [125] One
criticism of this reasoning is it often values those with disabilities less. [126]Others argue that Down syndrome
shouldn't be prevented or cured and that eliminating Down syndrome amounts to genocide. [127]
[128]
The disability rights movement does not have a position on screening,[129] although some members
consider testing and abortion discriminatory.[129] Some in the United States who are pro-life support abortion
if the fetus is disabled, while others do not.[130] Of a group of 40 mothers in the United States who have had
one child with Down syndrome, half agreed to screening in the next pregnancy. [130]
Within the US, some Protestants denominations see abortion as acceptable when a fetus has Down
syndrome,[131] while Orthodox Christians and Roman Catholics often do not.[131] Some of those against
screening refer to it as a form of "eugenics".[131] Disagreement exists within Islam regarding the acceptability
of abortion in those carrying a fetus with Down syndrome.[132] Some Islamic countries allow abortion, while
others do not.[132] Women may face stigmatization whichever decision they make.[133]
Advocacy groups
Advocacy groups for individuals with Down syndrome began to be form after the Second World War.
[134]
These were organizations advocating for the inclusion of people with Down syndrome into the general
school system and for a greater understanding of the condition among the general population, [134] as well as
groups providing support for families with children living with Down syndrome. [134] Before this individuals with
Down syndrom were often placed in mental hospitals or asylums. Organizations included the Royal Society
for Handicapped Children and Adults founded in the UK in 1946 by Judy Fryd,[134][135] Kobato Kai founded in
Japan in 1964,[134] the National Down Syndrome Congress founded in the United States in 1973 by Kathryn
McGee and others,[134][136] and the National Down Syndrome Society founded in 1979 in the United States.[134]
The first World Down Syndrome Day was held on 21 March 2006.[137] The day and month were chosen to
correspond with 21 and trisomy, respectively.[138] It was recognized by the United Nations General
Assembly in 2011.[137]
Research
See also: Down syndrome research and Mouse models of Down syndrome
Efforts are underway to determine how the extra chromosome 21 material causes Down syndrome, as
currently this is unknown,[139] and to develop treatments to improve intelligence in those with the syndrome.
[140]
One hope is to use stem cells.[139] Other methods being studied include the use of antioxidants, gamma
secretase inhibition,adrenergic agonists, and memantine.[141] Research is often carried out on an animal
model, the Ts65Dn mouse.[142]
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External links
media related to Down
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 Down syndrome at DMOZ
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Klinefelter syndrome
Not to be confused with XYY syndrome.
Klinefelter syndrome
XXY syndrome, Klinefelter's syndrome
47,XXY karyotype
Pronunciation /ˈklaɪnfɛltər/
Specialty medical genetics
ICD-10 Q98.0-Q98.4
ICD-9-CM 758.7
DiseasesDB 7189
MedlinePlus 000382
eMedicine ped/1252
Patient UK Klinefelter syndrome
MeSH D007713
[edit on Wikidata]
Klinefelter syndrome (KS) also known as 47,XXY or XXY, is the set of symptoms that result from two or
more X chromosomes in males.[1] The primary feature is sterility.[1] Often symptoms may be subtle and many
people do not realize they are affected. Sometimes symptoms are more prominent and may include weaker
muscles, greater height, poor coordination, less body hair, smaller genitals, breast growth, and less interest
in sex.[2] Often it is only at puberty that these symptoms are noticed.[3]Intelligence is usually normal;
however, reading difficulties and problems with speech are more common. Symptoms are typically more
severe if three or more X chromosomes are present. [2]
Klinefelter syndrome usually occurs randomly. An older mother might increase the risk slightly. The
condition is not inherited from one's parents.[4] The underlying mechanisms involves at least one extra X
chromosome in addition to a Y chromosome such that there is a total of 47 or more chromosomes rather
than usual 46.[5] KS is diagnosed by the genetic test known as a karyotype.[3]
While there is no cure, a number of treatments may help. [6] Physical therapy, speech and language
therapy, counselling, and adjustments of teaching methods may be useful. Testosterone replacement may
be used in those who have significantly low levels. Enlarged breasts may be removed by surgery. About
half of males affected with the help of assisted reproductive technology have a chance of having children;
however, this is expensive and carries risks. [7] Males appear to have a higher risk of breast cancer than
typical but still lower than that of females.[8] The condition has a nearly normal life expectancy.[6]
Klinefelter syndrome is one of the most common chromosomal disorders, occurring in 1:500 to 1:1000 live
male births.[4][9] It is named after Harry Klinefelter who identified the condition in the 1940s.[10] 1956 saw the
identification of the extra X chromosome.[11] Mice can also have the XXY syndrome, making them a useful
research model.[12]
Contents
[hide]

o 1.1Physical
o 1.2Cognitive and developmental
 2Cause
o 2.1Variations
 3Diagnosis
o 3.1Differential diagnosis
 4Treatment
o 4.1Infertility treatment
 5Prognosis
 6Epidemiology
 7History
 8See also
 9References
 10Further reading
Signs and symptoms[edit]

A person with typical untreated (surgery/hormones) Klinefelter 46,XY/47,XXY mosaic, diagnosed at age 19. Scar
from biopsy may be visible on left nipple.
While it is possible to characterise XXY males based on physical characteristics, substantial variation in
physical and developmental traits mean the only reliable method of positive or negative identification
is karyotype testing.
Physical[edit]
As babies and children, XXY males may have weaker muscles and reduced strength. As they grow older,
they tend to become taller than average. They may have less muscle control and coordination than other
boys of their age.[13]
During puberty, the physical traits of the syndrome become more evident; because these boys do not
produce as much testosterone as other boys, they have a less muscular body, less facial and body hair,
and broader hips. As teens, XXY males may develop breast tissue [14] and also have weaker bones, and a
lower energy level than other males.[13]
By adulthood, XXY males look similar to males without the condition, although they are often taller. In
adults, possible characteristics vary widely and include little to no sign of affectedness, a lanky, youthful
build and facial appearance, or a rounded body type with some degree of gynecomastia (increased breast
tissue).[15] Gynecomastia is present to some extent in about a third of affected individuals, a slightly higher
percentage than in the XY population. About 10% of XXY males havegynecomastia noticeable enough that
they may choose to have cosmetic surgery. [16]
Affected males are often infertile, or may have reduced fertility. Advanced reproductive assistance is
sometimes possible.[17]
The term hypogonadism in XXY symptoms is often misinterpreted to mean "small testicles" when it means
decreased testicular hormone/endocrine function. Because of this (primary) hypogonadism, individuals will
often have a low serum testosterone level but high serum follicle-stimulating hormone (FSH) and luteinizing
hormone (LH) levels.[18] Despite this misunderstanding of the term, however, it is true that XXY men may
also have microorchidism (i.e., small testicles).[18]
XXY males are also more likely than other men to have certain health problems that typically affect
females, such as autoimmune disorders, breast cancer, venous thromboembolic disease,
and osteoporosis.[13][19] In contrast to these potentially increased risks, it is currently thought that rare X-
linked recessive conditions occur less frequently in XXY males than in normal XY males, since these
conditions are transmitted by genes on the X chromosome, and people with two X chromosomes are
typically onlycarriers rather than affected by these X-linked recessive conditions. [citation needed]
Cognitive and developmental[edit]

Some degree of language learning or reading impairment may be present, [20] and neuropsychological
testing often reveals deficits in executive functions, although these deficits can often be overcome through
early intervention.[21] There may also be delays in motor development which can be addressed through
occupational therapy and physical therapy.[22] XXY males may sit up, crawl, and walk later than other
infants; they may also struggle in school, both academically and with sports. [13]
Cause[edit]
Birth of a cell with karyotype XXY due to a non-disjunction event of one X chromosome from a Y chromosome during meiosis
I in the male.
Birth of a cell with karyotype XXY due to a non-disjunction event of one X chromosome during meiosis II in the female.
The extra chromosome is retained because of a nondisjunction event during paternal or maternal meiosis

I (gametogenesis). Nondisjunction occurs when homologous chromosomes, in this case the X and Y or two
X sex chromosomes, fail to separate, producing a sperm with an X and a Y chromosome or an egg with
two X chromosomes. Fertilizing a normal (X) egg with this sperm produces an XXY offspring (Klinefelter).
Fertilizing a double X egg with a normal sperm also produces an XXY offspring (Klinefelter).
Another mechanism for retaining the extra chromosome is through a nondisjunction event during meiosis
II in the egg. Nondisjunction will occur when sister chromatids on the sex chromosome, in this case an X
and an X, fail to separate. (meiosis) An XX egg is produced which, when fertilized with a Y sperm, yields
XXY offspring. This XXY chromosome arrangement is one of the most common genetic variations from the
XY karyotype, occurring in about 1 in 500 live male births.[13] See also Triple X syndrome.
In mammals with more than one X chromosome, the genes on all but one X chromosome are not
expressed; this is known as X inactivation. This happens in XXY males as well as normal XX females.
[23]
However, in XXY males, a few genes located in thepseudoautosomal regions of their X chromosomes,
have corresponding genes on their Y chromosome and are capable of being expressed. [24]
The first published report of a man with a 47,XXY karyotype was by Patricia Jacobs and John
Strong at Western General Hospital inEdinburgh, Scotland in 1959.[25] This karyotype was found in a 24-
year-old man who had signs of Klinefelter syndrome. Jacobs described her discovery of this first reported
human or mammalian chromosome aneuploidy in her 1981 William Allan Memorial Award address.[26]
Variations[edit]
48,XXYY and 48,XXXY occur in 1 in 18,000–50,000 male births. The incidence of 49,XXXXY is 1 in 85,000
to 100,000 male births.[27]These variations are extremely rare. Additional chromosomal material can
contribute to cardiac, neurological, orthopedic and other anomalies.
Males with Klinefelter syndrome may have a mosaic 47,XXY/46,XY constitutional karyotype and varying
degrees of spermatogenic failure. Mosaicism 47,XXY/46,XX with clinical features suggestive of Klinefelter
syndrome is very rare. Thus far, only about 10 cases have been described in literature. [28]
Analogous XXY syndromes are known to occur in cats—specifically, the presence
of calico or tortoiseshell markings in male cats is an indicator of the relevant abnormal karyotype. As such,
male cats with calico or tortoiseshell markings are a model organism for Klinefelter syndrome.[29]
Diagnosis[edit]
Percentages of Klinefelter's diagnosis divided by age groups, with most diagnoses occurring in adulthood. [30]
About 10% of Klinefelter cases are found by prenatal diagnosis.[31] The first clinical features may appear in
early childhood or, more frequently, during puberty, such as lack of secondary sexual
characteristics and aspermatogenesis,[32] while tall stature as a symptom can be hard to diagnose during
puberty. Despite the presence of small testes, only a quarter of the affected males are recognized as
having Klinefelter syndrome at puberty.[33][34] Another quarter receive their diagnosis in late adulthood. About
64% of affected individuals are never recognized.[35] Often the diagnosis is made incidentally as a result of
examinations and medical visits for reasons not linked to the condition. [36]
The standard diagnostic method is the analysis of the chromosomes' karyotype on lymphocytes. In the
past, the observation of the Barr body was common practice as well.[34] To confirm mosaicism, it is also
possible to analyze the karyotype usingdermal fibroblasts or testicular tissue.[37]
Other methods may be: research of high serum levels of gonadotropins (follicle-stimulating
hormone and luteinizing hormone), presence of azoospermia, determination of the sex chromatin,
[38]
and prenatally via chorionic villus sampling or amniocentesis. A 2002 literature review of
elective abortion rates found that approximately 58% of pregnancies in the United States with a diagnosis
of Klinefelter syndrome were terminated.[39]
Differential diagnosis[edit]
The symptoms of Klinefelter syndrome are often variable; therefore, a karyotype analysis should be
ordered when small testes, infertility, gynecomastia, long legs/arms, developmental delay,
speech/language deficits, learning disabilities/academic issues and/or behavioral issues are present in an
individual.[5] The differential diagnosis for the Klinefelter syndrome can include the following
conditions: fragile X syndrome, Kallmann syndrome and Marfan syndrome. The cause of hypogonadism
can be attributed to many other different medical conditions.
There have been some reports of individuals with Klinefelter syndrome who also have other chromosome
abnormalities, such as Down syndrome.[40]
Treatment[edit]
The genetic variation is irreversible, however, individuals who want to look more masculine can
take testosterone.[41] Treating adolescents with implants of controlled release testosterone has shown good
results when appropriately monitored.[42] Hormone therapy is also useful in preventing the onset
of osteoporosis.
Often individuals that have noticeable breast tissue or hypogonadism experience depression and/or social
anxiety because they are outside of social norms. An academic term for this is psychosocial morbidity.[43] At
least one study indicates that planned and timed support should be provided for young men with Klinefelter
syndrome to ameliorate current poor psychosocial outcomes. [43] The surgical removal of the breasts may be
considered for both the psychological reasons and to reduce the risk of breast cancer. [44]
The use of behavioral therapy can mitigate any language disorders, difficulties at school and socialization.
An approach by occupational therapy is useful in children with Down syndrome who have dyspraxia motor.
[45]
Infertility treatment[edit]
Intracytoplasmic sperm injection.
By 2010 over 100 successful pregnancies have been reported using IVF technology with surgically
removed sperm material from males with Klinefelter syndrome.[46] Microdissection testicular sperm
extraction in adult men with Klinefelter syndrome reported success rates of up to 45%. [47]
Prognosis[edit]
Children with XXY differ little from other children. Although they can face problems during adolescence,
often emotional and behavioral, and difficulties at school, most of them can achieve full independence from
their families in adulthood. Most can lead a normal, healthy life.
The results of a study carried out on 87 Australian adults with the syndrome shows that those who have
had a diagnosis and appropriate treatment from a very young age had a significant benefit with respect to
those who had been diagnosed in adulthood.[48]
There is research suggesting Klinefelter syndrome substantially decreases life expectancy among affected
individuals, though the evidence is not definitive. [49] A 1985 publication identified a greater mortality mainly
due to diseases of the aortic valve, development of tumors and possible subarachnoid hemorrhages,
reducing life expectancy by about 5 years. [50] Later studies have reduced this estimated reduction to an
average of 2.1 years.[51] These results are still questioned data, are not absolute, and will need further
testing.[49]
Epidemiology[edit]
This syndrome, evenly spread in all ethnic groups, has a prevalence of 1-2 subjects every 1000 males in
the general population.[33][52][53][54] 3.1% of infertile males have Klinefelter syndrome. The syndrome is also the
main cause of male hypogonadism.[55]
According to a meta-analysis, the prevalence of the syndrome has increased over the past decades;
however, this does not appear to be correlated with the increase of the age of the mother at conception, as
no increase was observed in the prevalence of other trisomies of sex chromosomes (XXX and XYY).[56]
History[edit]
The syndrome was named after Harry Klinefelter, who, in 1942, worked with Fuller
Albright at Massachusetts General Hospital in Boston, Massachusetts, and first described it in the same
year.[15][32] The account given by Klinefelter came to be known as Klinefelter syndrome as his name
appeared first on the published paper, and seminiferous tubule dysgenesis was no longer used.
See also[edit]
 Aneuploidy
 Intersex
 Mosaic (genetics)
 True hermaphroditism
 Turner syndrome
 XXYY syndrome
References[edit]
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Human Development. 2013-10-25. Retrieved15 March 2015.
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36. Jump up^ Grzywa-Celińska A, Rymarz E, Mosiewicz J; Rymarz;
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K, Musilová J, Stĕpán J, Michalová K; Zemanová; Hána; Mayerová;
Pacovská; Musilová; Stĕpán; Michalová (April 1999). "[Molecular
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0272.1994.tb00773.x. PMID 8085664.
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syndromes: A systematic literature review". Prenatal
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Musoles F; Raga; Cuesta; Claramunt; Bonilla-Musoles (November
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6.doi:10.1136/jech.39.4.330. PMC 1052467 . PMID 4086964.
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70.doi:10.1038/sj.ejhg.5201956. PMID 18000523.
Further reading[edit]
 Virginia Isaacs Cover (2012). Living with Klinefelter Syndrome,
Trisomy X and 47,XYY: A Guide for Families and Individuals Affected
by Extra X and Y Chromosomes. ISBN 978-0-615-57400-4.
 Klinefelter syndrome at DMOZ
[hide]
Down syndrome
21
Edwards syndrome
18
Patau syndrome
13
Trisomies
Trisomy 9
Warkany syndrome 2
Cat eye syndrome/Trisomy 22
22
Trisomy 16
Monosomies/deletions 1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome
Wolf–Hirschhorn syndrome
Cri du chat/Chromosome 5q deletion syndrome
Williams syndrome
7

Jacobsen syndrome
11
Miller–Dieker syndrome/Smith–Magenis syndrome
17
DiGeorge syndrome
22
22q11.2 distal deletion syndrome
22
22q13 deletion syndrome
22
genomic imprinting
Angelman syndrome/Prader–Willi syndrome (15)
Distal 18q-/Proximal 18q-
Monosomy Turner syndrome (45,X)
Klinefelter syndrome (47,XXY)
48,XXYY
48,XXXY
49,XXXYY
49,XXXXY
Trisomy/tetrasomy, Triple X syndrome (47,XXX)
other karyotypes/mosaics 48,XXXX
49,XXXXX
47,XYY
48,XYYY
49,XYYYY
45,X/46,XY
Leukemia/lymphoma Lymphoid Burkitt's lymphoma t(8 MYC;14 IGH)
Follicular lymphoma t(14 IGH;18 BCL2)
Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH)
Anaplastic large-cell lymphoma t(2 ALK;5 NPM1)

Acute lymphoblastic leukemia
Philadelphia chromosome t(9 ABL; 22 BCR)
Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1)

Myeloid
Acute promyelocytic leukemia t(15 PML,17 RARA)
Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1)
Ewing's sarcoma t(11 FLI1; 22 EWS)
Synovial sarcoma t(x SYT;18 SSX)
Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB)
Other
Myxoid liposarcomat(12 DDIT3; 16 FUS)
Desmoplastic small-round-cell tumor t(11 WT1; 22 EWS)
Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1)
Fragile X syndrome
Uniparental disomy
XX male syndrome
Ring chromosome (13; 14; 15; 20)
GND: 4164211-9
Categories:
 Sex chromosome aneuploidies
 Syndromes
 Intersex and medicine
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Turner syndrome
Turner syndrome
Ullrich–Turner syndrome, gonadal dysgenesis, 45,X

Girl with Turner syndrome before and after an operation for neck-webbing
Specialty Pediatrics, medical genetics
ICD-10 Q96
ICD-9-CM 758.6
DiseasesDB 13461
MedlinePlus 000379
eMedicine ped/2330
Patient UK Turner syndrome
MeSH D014424
Orphanet 881
[edit on Wikidata]
Turner syndrome (TS) also known as 45,X, is a condition in which a female is partly or completely missing
an X chromosome.[1]Signs and symptoms vary among those affected. Often, a short and webbed neck, low-
set ears, low hairline at the back of the neck,short stature, and swollen hands and feet are seen at birth.
Typically, they are without menstrual periods, do not develop breasts, and are unable to have
children. Heart defects, diabetes, and low thyroid hormone occur more frequently. Most people with TS
have normal intelligence. Many, however, have troubles with spatial visualization such as that needed
for mathematics.[2] Vision and hearing problems occur more often. [3]
Turner syndrome is not usually inherited from a person's parents.[4] No environmental risks are known and
the mother's age does not play a role.[4][5] Turner syndrome is due to a chromosomal abnormality in which all
or part of one of the X chromosomes is missing or altered. While most people have 46 chromosomes,
people with TS usually have 45.[6] The chromosomal abnormality may be present in just some cells in which
case it is known as TS with mosaicism.[3] In these cases, the symptoms are usually fewer and possibly none
occur at all.[7] Diagnosis is based on physical signs and genetic testing.[8]
No cure for Turner syndrome is known. Treatment, however, may help with symptoms. Human growth
hormone injections during childhood may increase adult height. Estrogen replacement therapy can promote
development of the breasts and hips. Medical care is often required to manage other health problems with
which TS is associated.[9]
Turner syndrome occurs in between one in 2000[10] and one in 5000 females at birth.[11] All regions of the
world and cultures are affected about equally. [4] Generally people with TS have a shorter life expectancy,
mostly due to heart problems and diabetes.[3]Henry Turner first described the condition in 1938. In 1964, it
was determined to be due to a chromosomal abnormality.[12]
Contents
[hide]

o 1.1Prenatal
o 1.2Cardiovascular
o 1.3Skeletal
o 1.4Kidney
o 1.5Thyroid
o 1.6Diabetes
o 1.7Cognitive
o 1.8Reproductive
 2Cause
o 2.1Inheritance
 3Diagnosis
o 3.1Prenatal
o 3.2Postnatal
 4Treatment
 5Epidemiology
 6History
 7See also
 8References

Lymphedema, puffy legs of a newborn with Turner syndrome
Of the following common symptoms of Turner syndrome, an individual may have any combination of
symptoms and is unlikely to have all symptoms.
 Short stature
 Lymphedema (swelling) of the hands and feet of a newborn
 Broad chest (shield chest) and widely spaced nipples
 Low posterior hairline
 Low-set ears
 Reproductive sterility
 Rudimentary ovaries gonadal streak (underdeveloped gonadal structures that later become
fibrotic)
 Amenorrhoea, the absence of a menstrual period
 Increased weight, obesity
 Shortened metacarpal IV
 Small fingernails
 Characteristic facial features
 Webbed neck from cystic hygroma in infancy
 Aortic valve stenosis
 Coarctation of the aorta
 Bicuspid aortic valve
 Horseshoe kidney
 Visual impairments - sclera, cornea, glaucoma, etc.
 Ear infections and hearing loss
 High waist-to-hip ratio (the hips are not much bigger than the waist)
 Attention deficit hyperactivity disorder (problems with concentration, memory, attention with
hyperactivity seen mostly in childhood and adolescence)
 Nonverbal learning disability (problems with math, social skills, and spatial relations)
Other features may include a small lower jaw (micrognathia), cubitus valgus,[13] soft upturned nails, palmar
crease, and drooping eyelids. Less common are pigmented moles, hearing loss, and a high-arch palate
(narrow maxilla). Turner syndrome manifests itself differently in each female affected by the condition;
therefore, no two individuals share the same features.
While most of the physical findings are harmless, significant medical problems can be associated with the
syndrome.
Prenatal[edit]
Despite the excellent postnatal prognosis, 99% of Turner-syndrome conceptions are thought to end in
spontaneous abortion or stillbirth,[14] and as many as 15% of all spontaneous abortions have the 45,X
karyotype.[15] Among cases that are detected by routine amniocentesis or chorionic villus sampling, one
study found that the prevalence of Turner syndrome among tested pregnancies was 5.58 and 13.3 times
higher, respectively, than among live neonates in a similar population. [16]
Cardiovascular[edit]
Prevalence of cardiovascular malformations[edit]
The prevalence of cardiovascular malformations among patients with Turner syndrome ranges from
17% [17] to 45%.[18] The variations found in the different studies are mainly attributable to variations in
noninvasive methods used for screening and the types of lesions that they can characterize. [19] However,[20] it
could be simply attributable to the small number of subjects in most studies.
Different karyotypes may have differing prevalence of cardiovascular malformations. Two studies found a
prevalence of cardiovascular malformations of 30% [21] and 38%[22] in a group of pure 45,X monosomy.
Considering other karyotype groups, though, they reported a prevalence of 24.3% [21] and 11%[22] in patients
with mosaic X monosomy, and a prevalence of 11% in patients with X chromosomal structural
abnormalities.[21]
The higher prevalence in the group of pure 45,X monosomy is primarily due to a significant difference in the
prevalence of aortic valve abnormalities and coarctation of the aorta, the two most common cardiovascular
malformations.
Congenital heart disease[edit]

The most commonly observed are congenital obstructive lesions of the left side of the heart, leading to
reduced flow on this side of the heart. This includes bicuspid aortic valveand coarctation (narrowing) of the
aorta. More than 50% of the cardiovascular malformations of individuals with Turner syndrome in one study
were bicuspid aortic valves or coarctation of the aorta (usually preductal), alone or in combination. [20]
Other congenital cardiovascular malformations, such as partial anomalous venous drainage and aortic
valve stenosis or aortic regurgitation, are also more common in Turner syndrome than in the general
population. Hypoplastic left heart syndrome represents the most severe reduction in left-sided structures.
Bicuspid aortic valve[edit]
Up to 15% of adults with Turner syndrome have bicuspid aortic valves, meaning only two, instead of three,
parts to the valves in the main blood vessel leading from the heart are present. Since bicuspid valves are
capable of regulating blood flow properly, this condition may go undetected without regular screening.
However, bicuspid valves are more likely to deteriorate and later fail. Calcification also occurs in the valves,
[23]
which may lead to a progressive valvular dysfunction as evidenced by aortic stenosis or regurgitation. [24]
With a prevalence from 12.5%[21] to 17.5% (Dawson-Falk et al., 1992), bicuspid aortic valve is the most
common congenital malformation affecting the heart in this syndrome. It is usually isolated, but it may be
seen in combination with other anomalies, particularly coarctation of the aorta.
Coarctation of the aorta[edit]
Between 5% and 10% of those born with Turner syndrome have coarctation of the aorta, a congenital
narrowing of the descending aorta, usually just distal to the origin of the left subclavian artery (the artery
that branches off the arch of the aorta to the left arm) and opposite to the duct (and so termed
"juxtaductal"). Estimates of the prevalence of this malformation in patients with Turner syndrome range
from 6.9[21] to 12.5% . A coarctation of the aorta in a female is suggestive of Turner syndrome, and suggests
the need for further tests, such as a karyotype.
Partial anomalous venous drainage[edit]
This abnormality is a relatively rare congenital heart disease in the general population. The prevalence of
this abnormality also is low (around 2.9%) in Turner syndrome. However, its relative risk is 320 in
comparison with the general population. Strangely, Turner syndrome seems to be associated with unusual
forms of partial anomalous venous drainage.[21][25]
In a patient with Turner syndrome, these left-sided cardiovascular malformations can result in an increased
susceptibility to bacterial endocarditis. Therefore, prophylactic antibiotics should be considered when
procedures with a high risk of endocarditis are performed, such as dental cleaning. [24]
Turner syndrome is often associated with persistent hypertension, sometimes in childhood. In the majority
of Turner syndrome patients with hypertension, no specific cause is known. In the remainder, it is usually
associated with cardiovascular or kidney abnormalities, including coarctation of the aorta.
Aortic dilation, dissection, and rupture[edit]

Two studies have suggested aortic dilatation in Turner syndrome, typically involving the root of the
ascending aorta and occasionally extending through the aortic arch to the descending aorta, or at the site
of previous coarctation of the aorta repair.[26]
 A study that evaluated 28 girls with Turner syndrome found a significantly greater mean aortic root
diameter in patients with Turner syndrome than in the control group (matched for body surface area).
Nonetheless, the aortic root diameters found in Turner syndrome patients were still well within the
limits.[27]
 This has been confirmed by a study that evaluated 40 patients with Turner syndrome. [18] The study
presented basically the same findings: a greater mean aortic root diameter, which nevertheless
remains within the normal range for body surface area.
Whether aortic root diameters that are relatively large for body surface area but still well within normal limits
imply a risk for progressive dilatation remains unproven.[20]
Prevalence of aortic abnormalities[edit]
The prevalence of aortic root dilatation ranges from 8.8 [26] to 42%[24] in patients with Turner syndrome. Even
if not every aortic root dilatation necessarily goes on to an aortic dissection (circumferential or transverse
tear of the intima), complications such as dissection, aortic rupture resulting in death may occur. The
natural history of aortic root dilatation is still unknown, but it is linked to aortic dissection and rupture, which
has a high mortality rate.[28]
Aortic dissection affects 1 to 2% of patients with Turner syndrome. As a result, any aortic root dilatation
should be seriously taken into account, as it could become a fatal aortic dissection. Routine surveillance is
highly recommended.[24]
Risk factors for aortic rupture[edit]
Cardiovascular malformations (typically bicuspid aortic valve, coarctation of the aorta, and some other left-
sided cardiac malformations) and hypertension predispose to aortic dilatation and dissection in the general
population. Indeed, these same risk factors are found in more than 90% of patients with Turner syndrome
who develop aortic dilatation. Only a small number of patients (around 10%) have no apparent
predisposing risk factors. The risk of hypertension is increased three-fold in patients with Turner syndrome.
Because of its relation to aortic dissection, blood pressure must be regularly monitored and hypertension
should be treated aggressively with an aim to keep blood pressure below 140/80 mmHg. As with the other
cardiovascular malformations, complications of aortic dilatation is commonly associated with 45,X
karyotype.[24]
Pathogenesis of aortic dissection and rupture [edit]
The exact role that all these risk factors play in the process leading to such fatal complications is still quite
unclear. Aortic root dilatation is thought to be due to a mesenchymal defect as pathological evidence of
cystic medial necrosis has been found by several studies. The association between a similar defect and
aortic dilatation is well established in such conditions such as Marfan syndrome. Also, abnormalities in
other mesenchymal tissues (bone matrix and lymphatic vessels) suggests a similar primary mesenchymal
defect in patients with Turner syndrome.[26] However, no evidence suggests that patients with Turner
syndrome have a significantly higher risk of aortic dilatation and dissection in absence of predisposing
factors. So, the risk of aortic dissection in Turner syndrome appears to be a consequence of structural
cardiovascular malformations and hemodynamic risk factors rather than a reflection of an inherent
abnormality in connective tissue. The natural history of aortic root dilatation is unknown, but because of its
lethal potential, this aortic abnormality needs to be carefully followed.
Skeletal[edit]
Normal skeletal development is inhibited due to a large variety of factors, mostly hormonal. The average
height of a woman with Turner syndrome, in the absence of growth hormone treatment, is 4 ft 7
in (140 cm). Patients with Turner's mosaicism can reach normal average height.
The fourth metacarpal bone (fourth toe and ring finger) may be unusually short, as may the fifth.
Due to inadequate production of estrogen, many of those with Turner syndrome develop osteoporosis. This
can decrease height further, as well as exacerbate the curvature of the spine, possibly leading to scoliosis.
It is also associated with an increased risk of bone fractures.
Kidney[edit]
About one-third of all women with Turner syndrome have one of three kidney abnormalities:
1. A single, horseshoe-shaped kidney on one side of the body

2. An abnormal urine-collecting system
3. Poor blood flow to the kidneys
Some of these conditions can be corrected surgically. Even with these abnormalities, the kidneys of most
women with Turner syndrome function normally. However, as noted above, kidney problems may be
associated with hypertension.
Thyroid[edit]
Approximately one-third of all women with Turner syndrome have a thyroid disorder. [29] Usually it
is hypothyroidism, specifically Hashimoto's thyroiditis. If detected, it can be easily treated with thyroid
hormone supplements.
Diabetes[edit]
Women with Turner syndrome are at a moderately increased risk of developing type 1 diabetes in
childhood and a substantially increased risk of developing type 2 diabetes by adult years. The risk of
developing type 2 diabetes can be substantially reduced by maintaining a healthy weight.
Cognitive[edit]
Turner syndrome does not typically cause intellectual disability or impair cognition. However, learning
difficulties are common among women with Turner syndrome, particularly a specific difficulty in perceiving
spatial relationships, such as nonverbal learning disorder. This may also manifest itself as a difficulty with
motor control or withmathematics.[citation needed] While it is not correctable, in most cases it does not cause
difficulty in daily living. Most Turner syndrome patients are employed as adults and lead productive lives.
Also, a rare variety of Turner syndrome, known as "Ring-X Turner syndrome", has about a 60% association
with intellectual disability[clarification needed]. This variety accounts for around 2–4% of all Turner syndrome cases. [30]
Reproductive[edit]
Women with Turner syndrome are almost universally infertile. While some women with Turner syndrome
have successfully become pregnant and carried their pregnancies to term, this is very rare and is generally
limited to those women whose karyotypes are not 45,X. [31][32] Even when such pregnancies do occur, there is
a higher than average risk ofmiscarriage or birth defects, including Turner Syndrome or Down Syndrome.
[33]
Some women with Turner syndrome who are unable to conceive without medical intervention may be
able to use IVF or other fertility treatments.[34]
Usually estrogen replacement therapy is used to spur growth of secondary sexual characteristics at the
time when puberty should onset. While very few women with Turner Syndrome menstruate spontaneously,
estrogen therapy requires a regular shedding of the uterine lining ("withdrawal bleeding") to prevent its
overgrowth. Withdrawal bleeding can be induced monthly, like menstruation, or less often, usually every
three months, if the patient desires. Estrogen therapy does not make a woman with nonfunctional ovaries
fertile, but it plays an important role in assisted reproduction; the health of the uterus must be maintained
with estrogen if an eligible woman with Turner Syndrome wishes to use IVF (using donated oocytes).
Turner syndrome is a cause of primary amenorrhea, premature ovarian failure (hypergonadotropic
hypogonadism), streak gonads and infertility. Failure to develop secondary sex characteristics (sexual
infantilism) is typical.
Especially in mosaic cases of Turner syndrome that contains Y-chromosome (e.g. 45,X/46,XY) due to the
risk of development of ovarian malignancy (most common is gonadoblastoma) gonadectomy is
recommended.[29] [35] Turner syndrome is characterized by primary amenorrhoea, premature ovarian
failure, streak gonads and infertility. However, technology (especially oocyte donation) provides the
opportunity of pregnancy in these patients.
As more women with Turner syndrome complete pregnancy thanks to modern techniques to treat infertility,
it has to be noted that pregnancy may be a risk of cardiovascular complications for the mother. Indeed,
several studies had suggested an increased risk for aortic dissection in pregnancy. [26] Three deaths have
even been reported. The influence of estrogen has been examined but remains unclear. It seems that the
high risk of aortic dissection during pregnancy in women with Turner syndrome may be due to the
increased hemodynamic load rather than the high estrogen rate.[24] Of course these findings are important
and need to be remembered while following a pregnant patient with Turner syndrome.
Cause[edit]
Turner syndrome is caused by the absence of one complete or partial copy of the X chromosome in some
or all the cells. The abnormal cells may have only one X (monosomy) (45,X) or they may be affected by
one of several types of partial monosomy like a deletion of the short p arm of one X chromosome
(46,X,del(Xp)) or the presence of anisochromosome with two q arms (46,X,i(Xq))[36] In mosaic individuals,
cells with X monosomy (45,X) may occur along with cells that are normal (46,XX), cells that have partial
monosomies, or cells that have a Y chromosome (46,XY). [36] The presence of mosaicism is estimated to be
relatively common in affected individuals (67–90%).[36]
Inheritance[edit]
In the majority of cases where monosomy occurs, the X chromosome comes from the mother. [37] This may
be due to a nondisjunction in the father. Meiotic errors that lead to the production of X with p arm deletions
or abnormal Y chromosomes are also mostly found in the father.[38] Isochromosome X or ring
chromosome X on the other hand are formed equally often by both parents. [38] Overall, the functional X
chromosome usually comes from the mother.
In most cases, Turner syndrome is a sporadic event, and for the parents of an individual with Turner
syndrome the risk of recurrence is not increased for subsequent pregnancies. Rare exceptions may include
the presence of a balanced translocation of the X chromosome in a parent, or where the mother has 45,X
mosaicism restricted to her germ cells.[39]
Diagnosis[edit]
Prenatal[edit]
45,X karyotype, showing an unpaired X at the lower right
Turner syndrome may be diagnosed by amniocentesis or chorionic villus sampling during pregnancy.

Usually, fetuses with Turner syndrome can be identified by abnormal ultrasound findings (i.e., heart defect,
kidney abnormality, cystic hygroma, ascites). In a study of 19 European registries, 67.2% of prenatally
diagnosed cases of Turner Syndrome were detected by abnormalities on ultrasound. 69.1% of cases had
one anomaly present, and 30.9% had two or more anomalies. [40]
An increased risk of Turner syndrome may also be indicated by abnormal triple or quadruple maternal
serum screen. The fetuses diagnosed through positive maternal serum screening are more often found to
have a mosaic karyotype than those diagnosed based on ultrasonographic abnormalities, and conversely
those with mosaic karyotypes are less likely to have associated ultrasound abnormalities. [40]
Although the recurrence risk is not increased, genetic counseling is often recommended for families who
have had a pregnancy or child with Turner syndrome.
Postnatal[edit]
Turner syndrome can be diagnosed postnatally at any age. Often, it is diagnosed at birth due to heart
problems, an unusually wide neck or swelling of the hands and feet. However, it is also common for it to go
undiagnosed for several years, typically until the girl reaches the age of puberty/adolescence and she fails
to develop properly (the changes associated with puberty do not occur). In childhood, a short stature can
be indicative of Turner syndrome.[41]
A test, called a karyotype or a chromosome analysis, analyzes the chromosomal composition of the
individual. This is the test of choice to diagnose Turner syndrome.
Treatment[edit]
As a chromosomal condition, there is no cure for Turner syndrome. However, much can be done to
minimize the symptoms. For example:[42]
 Growth hormone, either alone or with a low dose of androgen, will increase growth and probably
final adult height. Growth hormone is approved by the U.S. Food and Drug Administration for treatment
of Turner syndrome and is covered by many insurance plans. [42][43] There is evidence that this is
effective, even in toddlers.[44]
 Estrogen replacement therapy such as the birth control pill, has been used since the condition was
described in 1938 to promote development of secondary sexual characteristics. Estrogens are crucial
for maintaining good bone integrity, cardiovascular health and tissue health. [42] Women with Turner
Syndrome who do not have spontaneous puberty and who are not treated with estrogen are at high
risk for osteoporosis and heart conditions.
 Modern reproductive technologies have also been used to help women with Turner syndrome
become pregnant if they desire. For example, a donor egg can be used to create an embryo, which is
carried by the Turner syndrome woman.[42]
 Uterine maturity is positively associated with years of estrogen use, history of spontaneous
menarche, and negatively associated with the lack of current hormone replacement therapy. [45]
Epidemiology[edit]
Approximately 99 percent of all fetuses with Turner syndrome result in spontaneous termination during the
first trimester.[46] Turner syndrome accounts for about 10 percent of the total number of spontaneous
abortions in the United States.[29] The incidence of Turner syndrome in live female births is believed to be
around 1 in 2000.
History[edit]
The syndrome is named after Henry Turner, an endocrinologist from Illinois, who described it in 1938.[47] In
Europe, it is often called Ullrich–Turner syndrome or even Bonnevie–Ullrich–Turner syndrome to
acknowledge that earlier cases had also been described by European doctors.
The first published report of a female with a 45,X karyotype was in 1959 by Dr. Charles Ford and
colleagues in Harwell, Oxfordshire, and Guy's Hospital in London.[48] It was found in a 14-year-old girl with
signs of Turner syndrome.
See also[edit]
 Gonadal dysgenesis, for related abnormalities,
 Other human sex chromosome aneuploids:
 XYY syndrome,
 Klinefelter syndrome (XXY),
 Triple X syndrome,
 Dermatoglyphics,
 Noonan syndrome, a disorder which is often confused with Turner syndrome because of several
physical features that they have in common.
References[edit]
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Engl. J. Med. 351 (12): 1227–38. doi:10.1056/NEJMra030360. PMID 15371580.
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patients with Turner's syndrome. Italian Study Group for Turner Syndrome (ISGTS)". J.
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1994)."Prevalence of cardiovascular malformations and association with karyotypes in Turner's
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. PMID 7826114.
23. Jump up^ Aortic Valve, Bicuspid at eMedicine
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Tsingos E, Cacciari E (1999). "Turner's syndrome: cardiologic profile according to the different
chromosomal patterns and long-term clinical follow-Up of 136 nonpreselected patients".Pediatr
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26. ^ Jump up to:a b c d Lin AE, Lippe B, Rosenfeld RG (Jul 1998). "Further delineation of aortic dilation,
dissection, and rupture in patients with Turner syndrome". Pediatrics. 102 (1):
e12.doi:10.1542/peds.102.1.e12. PMID 9651464.
27. Jump up^ Allen DB, Hendricks SA, Levy JM (Aug 1986). "Aortic dilation in Turner
syndrome". J Pediatr. 109 (2): 302–5. doi:10.1016/S0022-3476(86)80001-4. PMID 3734967.
28. Jump up^ Concha Ruiz M (2006). "Surgical treatment of the aortic root dilatation". An R Acad
Nac Med (Madr) (in Spanish). 123 (3): 557–68; discussion 569–71. PMID 17451098.
29. ^ Jump up to:a b c Elsheikh, M.; Dunger, D. B.; Conway, G. S.; Wass, J. A. H. (February
2002)."Turner's Syndrome in Adulthood". Endocrine Reviews. 23 (1): 120–
140.doi:10.1210/edrv.23.1.0457. Retrieved 5 February 2016.
30. Jump up^ Berkovitz G, Stamberg J, Plotnick LP, Lanes R (Jun 1983). "Turner syndrome
patients with a ring X chromosome". Clin Genet. 23 (6): 447–53. doi:10.1111/j.1399-
0004.1983.tb01980.x. PMID 6883789.
31. Jump up^ Kaneko N, Kawagoe S, Hiroi M (1990). "Turner's syndrome—review of the literature
with reference to a successful pregnancy outcome". Gynecol Obstet Invest. 29 (2): 81–
7.doi:10.1159/000293307. PMID 2185981.
32. Jump up^ Livadas S, Xekouki P, Kafiri G, Voutetakis A, Maniati-Christidi M, Dacou-Voutetakis
C (2005). "Spontaneous pregnancy and birth of a normal female from a woman with Turner syndrome
and elevated gonadotropins". Fertility and Sterility. 83 (3): 769–
72.doi:10.1016/j.fertnstert.2004.11.007. PMID 15749515.
33. Jump up^ Nielsen J, Sillesen I, Hansen KB (1979). "Fertility in women with Turner's
syndrome. Case report and review of literature". British journal of obstetrics and gynaecology. 86(11):
833–5. doi:10.1111/j.1471-0528.1979.tb10706.x. PMID 508669.
34. Jump up^ Hovatta O (1999). "Pregnancies in women with Turner's syndrome". Annals of
Medicine. 31 (2): 106–10. doi:10.3109/07853899908998785. PMID 10344582.
35. Jump up^ Gravholt, Claus Højbjerg; Fedder, Jens; Weis, Rune Naeraa; Müller, Jørn (July 1,
2013). "Occurrence of Gonadoblastoma in Females with Turner Syndrome and Y Chromosome
Material: A Population Study". Journal of Clinical Endocrinology &
Metabolism. 85 (9). doi:10.1210/jcem.85.9.6800. Retrieved 5 February 2016.
36. ^ Jump up to:a b c Crespi B (2008). "Turner syndrome and the evolution of human sexual
dimorphism". Evolutionary Applications. 1 (3): 449–461. doi:10.1111/j.1752-4571.2008.00017.x.
37. Jump up^ Monroy N, López M, Cervantes A, García-Cruz D, Zafra G, Canún S, Zenteno JC,
Kofman-Alfaro S (2002). "Microsatellite analysis in Turner syndrome: Parental origin of X chromosomes
and possible mechanism of formation of abnormal chromosomes".American Journal of Medical
Genetics. 107 (3): 181–189. doi:10.1002/ajmg.10113.PMID 11807897.
38. ^ Jump up to:a b Uematsu A, Yorifuji T, Muroi J, Kawai M, Mamada M, Kaji M, Yamanaka C, Momoi
T, Nakahata T (2002). "Parental origin of normal X chromosomes in Turner syndrome patients with
various karyotypes: Implications for the mechanism leading to generation of a 45,X
karyotype". American Journal of Medical Genetics. 111 (2): 134–
139.doi:10.1002/ajmg.10506. PMID 12210339.
39. Jump up^ Frías JL, Davenport ML; Davenport; Committee on Genetics Section on
Endocrinology (2003). "Health Supervision for Children with Turner Syndrome". Pediatrics. 111 (3):
692–702. doi:10.1542/peds.111.3.692. PMID 12612263.
40. ^ Jump up to:a b http://www.turner-syndrom.dk/doc/videnskab/Prenatalcounseling9.pdf
41. Jump up^ http://www.medicinenet.com/turner_syndrome/page2.htm#tocd
42. ^ Jump up to:a b c d Turner Syndrome Society of the United States. "FAQ 6. What can be done?".
43. Jump up^ Bolar K, Hoffman AR, Maneatis T, Lippe B (2008). "Long-term safety of
recombinant human growth hormone in Turner syndrome". J. Clin. Endocrinol. Metab. 93 (2): 344–
51.doi:10.1210/jc.2007-1723. PMID 18000090.
44. Jump up^ Davenport ML, Crowe BJ, Travers SH, Rubin K, Ross JL, Fechner PY, Gunther DF,
Liu C, Geffner ME, Thrailkill K, Huseman C, Zagar AJ, Quigley CA (2007). "Growth hormone treatment
of early growth failure in toddlers with Turner syndrome: a randomized, controlled, multicenter trial". J
Clin Endocrinol Metab. 92 (9): 3406–16.doi:10.1210/jc.2006-2874. PMID 17595258.
45. Jump up^ "Uterine Development in Turner Syndrome". GGH Journal. 24 (1).
2008. ISSN 1932-9032.
46. Jump up^ Urbach A, Benvenisty N; Benvenisty (2009). "Studying early lethality of 45,XO
(Turner's syndrome) embryos using human embryonic stem cells". PLoS ONE. 4 (1):
e4175.doi:10.1371/journal.pone.0004175. PMC 2613558 . PMID 19137066.
47. Jump up^ Turner HH (1938). "A syndrome of infantilism, congenital webbed neck,
and cubitus valgus". Endocrinology. 23 (5): 566–74. doi:10.1210/endo-23-5-566.
48. Jump up^ Ford CE, Jones KW, Polani PE, De Almeida JC, Briggs JH (1959). "A sex-
chromosome anomaly in a case of gonadal dysgenesis (Turner's syndrome)". The Lancet. 273 (7075):
711–3. doi:10.1016/S0140-6736(59)91893-8. PMID 13642858.
 Bondy CA; Turner Syndrome Study, Group (2007). "Care of girls and women with Turner
syndrome: A guideline of the Turner Syndrome Study Group". J Clin Endocrinol Metab. 92 (1): 10–
25. doi:10.1210/jc.2006-1374. PMID 17047017.
 Turner Syndrome Society of the United States
 Turner Syndrome at the National Institute of Child Health and Human Development
 Turner Syndrome at NIH's Office of Rare Diseases
 Endocrine and Metabolic Diseases Information Service
[hide]
Down syndrome
21
Edwards syndrome
18
Patau syndrome
13
Trisomies
Trisomy 9
Warkany syndrome 2
Cat eye syndrome/Trisomy 22
22
Trisomy 16
Monosomies/deletions 1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome
Wolf–Hirschhorn syndrome
Cri du chat/Chromosome 5q deletion syndrome

Williams syndrome
Jacobsen syndrome
11
Miller–Dieker syndrome/Smith–Magenis syndrome
17
DiGeorge syndrome
22
22q11.2 distal deletion syndrome
22
22q13 deletion syndrome
22
genomic imprinting
Angelman syndrome/Prader–Willi syndrome (15)
Distal 18q-/Proximal 18q-
Monosomy
Turner syndrome (45,X)
Klinefelter syndrome (47,XXY)
48,XXYY
48,XXXY
49,XXXYY
49,XXXXY
Trisomy/tetrasomy,
Triple X syndrome (47,XXX)
other karyotypes/mosaics
48,XXXX
49,XXXXX
47,XYY
48,XYYY
49,XYYYY
45,X/46,XY
Burkitt's lymphoma t(8 MYC;14 IGH)
Follicular lymphoma t(14 IGH;18 BCL2)
Lymphoid
Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH)
Anaplastic large-cell lymphoma t(2 ALK;5 NPM1)
Leukemia/lymphoma Acute lymphoblastic leukemia
Philadelphia chromosome t(9 ABL; 22 BCR)
Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1)

Myeloid
Acute promyelocytic leukemia t(15 PML,17 RARA)
Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1)
Ewing's sarcoma t(11 FLI1; 22 EWS)
Synovial sarcoma t(x SYT;18 SSX)
Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB)
Other
Myxoid liposarcomat(12 DDIT3; 16 FUS)
Desmoplastic small-round-cell tumor t(11 WT1; 22 EWS)
Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1)
Fragile X syndrome
Uniparental disomy
XX male syndrome
Ring chromosome (13; 14; 15; 20)
GND: 4186484-0
NDL: 01112797
Categories:
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 Genodermatoses
 Rare diseases
 Growth disorders
 Intersex and medicine
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Phenylketonuria
"PKU" redirects here. For other uses, see PKU (disambiguation).
Phenylketonuria
Phenylalanine hydroxylase deficiency, PAH deficiency, Folling
disease[1]
Phenylalanine
Specialty medical genetics, pediatrics
ICD-10 E70.0
ICD-9-CM 270.1
OMIM 261600 261630
DiseasesDB 9987
MedlinePlus 001166
eMedicine ped/1787 derm/712article/947781
Patient UK Phenylketonuria
MeSH D010661
Phenylalanine Hydroxylase Deficiency

GeneReviews
Orphanet 716 226
[edit on Wikidata]
Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of
the amino acid phenylalanine.[2]Untreated PKU can lead to intellectual disability, seizures, behavioral
problems, and mental disorder. It may also result in a musty smell and lighter skin. Babies born to mothers
who have poorly treated PKU may have heart problems, a small head, and low birth weight.[1]
Phenylketonuria is a genetic disorder inherited from a person's parents. It is due to mutations in
the PAH gene which results in low levels of the enzyme phenylalanine hydroxylase. This results in the build
up of dietary phenylalanine to potentially toxic levels. It isautosomal recessive meaning that both copies of
the gene must be mutated for the condition to develop. There are two main types, classic PKU and variant
PKU, depending on if any enzyme function remains. Those with one copy of a mutated gene typically do
not have symptoms.[1] Many countries have newborn screening programs for the disease.[2]
Treatment is with a diet low in foods that contain phenylalanine and special supplements. Babies should
use a special formula. The diet should begin as soon as possible after birth and be lifelong. [3] People who
are diagnosed early and maintain a strict diet can have normal health and a normal life span. Effectiveness
is monitored through periodic blood tests. [4] The medicationsapropterin dihydrochloride may be useful in
some.[3]
Phenylketonuria affects about one in 10,000 to 25,000 babies. [1][5] Males and females are affected equally.
[6]
The disease was discovered in 1934 by Ivar Asbjørn Følling with the importance of diet determined in
1953.[5] Gene therapy, while promising, requires a great deal more study as of 2014. [7]
Contents
[hide]

 2Genetics
 3Pathophysiology
o 3.1Classical PKU
o 3.2Tetrahydrobiopterin-deficient hyperphenylalaninemia
o 3.3Metabolic pathways
 4Screening
 5Treatment
o 5.1Diet
o 5.2Supplements
o 5.3Women
 6Epidemiology
 7History
 8Etymology and pronunciation
 9Research
 10See also
 11References

Because the mother's body is able to break down phenylalanine during pregnancy, infants with PKU are
normal at birth. The disease is not detectable by physical examination at that time, because no damage
has yet been done. However, a blood test can reveal elevated phenylalanine levels after one or two days of
normal infant feeding. This is the purpose of newborn screening, to detect the disease with a blood test
before any damage is done, so that treatment can prevent the damage from happening.
If a child is not diagnosed during the routine newborn screening test (typically performed 2–7 days after
birth, using samples drawn by neonatal heel prick), and a phenylalanine restricted diet is not introduced,
then phenylalanine levels in the blood will increase over time. Toxic levels of phenylalanine (and insufficient
levels of tyrosine) can interfere with infant development in ways which have permanent effects. The
disease may present clinically with seizures, hypopigmentation (excessively fair hair and skin), and a
"musty odor" to the baby's sweat and urine (due to phenylacetate, a carboxylic acid produced by the
oxidation of phenylketone). In most cases, a repeat test should be done at approximately two weeks of age
to verify the initial test and uncover any phenylketonuria that was initially missed.
Untreated children often fail to attain early developmental milestones, develop microcephaly, and
demonstrate progressive impairment of cerebral function. Hyperactivity, EEGabnormalities, and seizures,
and severe learning disabilities are major clinical problems later in life. A characteristic "musty or mousy"
odor on the skin, as well as a predisposition for eczema, persist throughout life in the absence of treatment.
The damage done to the brain if PKU is untreated during the first months of life is not reversible. It is critical
to control the diet of infants with PKU very carefully so that the brain has an opportunity to develop
normally. Affected children who are detected at birth and treated are much less likely to develop
neurological problems or have seizures and intellectual disability (though such clinical disorders are still
possible.)
In general, however, outcomes for people treated for PKU are good. Treated people may have no
detectable physical, neurological, or developmental problems at all. Many adults with PKU who were
diagnosed through newborn screening and have been treated since birth have high educational
achievement, successful careers, and fulfilling family lives.[8][9]
Genetics[edit]
Phenylketonuria is inherited in anautosomal recessive fashion
PKU is an autosomal recessive metabolic genetic disorder. As an autosomal recessive disorder, two

PKU alleles are required for an individual to exhibit symptoms of the disease. If both parents are carriers for
PKU, there is a 25% chance any child they have will be born with the disorder, a 50% chance the child will
be a carrier, and a 25% chance the child will neither develop nor be a carrier for the disease.
PKU is characterized by homozygous or compound heterozygous mutations in the gene for the hepatic
enzyme phenylalanine hydroxylase (PAH), rendering it nonfunctional.[10]:541 This enzyme is necessary to
metabolize the amino acid phenylalanine (Phe) to the amino acid tyrosine (Tyr). When PAH activity is
reduced, phenylalanine accumulates and is converted into phenylpyruvate (also known as phenylketone),
which can be detected in the urine.[11]
Carriers of a single PKU allele do not exhibit symptoms of the disease but appear to be protected to some
extent against the fungal toxin ochratoxin A.[12] This accounts for the persistence of the allele in certain
populations in that it confers a selective advantage—in other words, being a heterozygote is advantageous.
[13]
The PAH gene is located on chromosome 12 in the bands 12q22-q24.1. More than 400 disease-causing
mutations have been found in the PAH gene. This is an example of allelic genetic heterogeneity.
Phenylketonuria can exist in mice, which have been extensively used in experiments into finding an
effective treatment for it.[14] Themacaque monkey's genome was recently sequenced, and the gene
encoding phenylalanine hydroxylase was found to have a sequence that, in humans, would be considered
a PKU mutation.[15]
Pathophysiology[edit]
When Phe cannot be metabolized by the body, a typical diet that would be healthy for people without PKU
causes abnormally high levels of Phe to accumulate in the blood, which is toxic to the brain. If left
untreated, complications of PKU include severe intellectual disability, brain function abnormalities,
microcephaly, mood disorders, irregular motor functioning, and behavioral problems such as attention
deficit hyperactivity disorder, as well as physical symptoms such as a "musty" odor, eczema, and unusually
light skin and hair coloration.
Classical PKU[edit]
Classical PKU, and its less severe forms "mild PKU" and "mild hyperphenylalaninemia" are caused by a
mutated gene for the enzyme phenylalanine hydroxylase (PAH), which converts the amino acid
phenylalanine ("Phe") to other essential compounds in the body, in particular tyrosine. Tyrosine is a
conditionally essential Amino acid for PKU patients because without PAH it cannot be produced in the body
through the breakdown of phenylalanine. Tyrosine is necessary for the production of neurotransmitters like
epinephrine, norepinephrine, and dopamine. [16]
PAH deficiency causes a spectrum of disorders, including classic phenylketonuria (PKU) and mild
hyperphenylalaninemia (also known as "hyperphe" or "mild HPA"), a less severe accumulation of
phenylalanine. Patients with "hyperphe" may have more functional PAH enzyme and be able to tolerate
larger amounts of phenylalanine in their diets than those with classic PKU, but unless dietary intake is at
least somewhat restricted, their blood Phe levels are still higher than the levels in people with normal PAH
activity.[17]
Phenylalanine is a large, neutral amino acid (LNAA). LNAAs compete for transport across the blood–brain
barrier (BBB) via the large neutral amino acid transporter (LNAAT). If phenylalanine is in excess in the
blood, it will saturate the transporter. Excessive levels of phenylalanine tend to decrease the levels of other
LNAAs in the brain. As these amino acids are necessary for protein and neurotransmitter synthesis, Phe
buildup hinders the development of the brain, causing intellectual disability.[18]
Recent research suggests that neurocognitive, psychosocial, quality of life, growth, nutrition, bone
pathology are slightly suboptimal even for patients who are treated and maintain their Phe levels in the
target range, if their diet is not supplemented with other amino acids. [19]
Classic PKU dramatically affects myelination and white matter tracts in untreated infants; this may be one
major cause of neurological disorders associated with phenylketonuria. Differences in white matter
development are observable with magnetic resonance imaging. Abnormalities in gray matter can also be
detected, particularly in the motor and pre-motor cortex, thalamus and the hippocampus. [20]
It was recently suggested that PKU may resemble amyloid diseases, such as Alzheimer's disease and
Parkinson's disease, due to the formation of toxic amyloid-like assemblies of phenylalanine. [21]
Other non-PAH mutations can also cause PKU.[citation needed]
Tetrahydrobiopterin-deficient hyperphenylalaninemia[edit]
A rarer form of hyperphenylalaninemia occurs when the PAH enzyme is normal, and a defect is found in
the biosynthesis or recycling of the cofactor tetrahydrobiopterin (BH4).[22]BH4 (called biopterin) is necessary
for proper activity of the enzyme PAH, and this coenzyme can be supplemented as treatment. Those who
suffer from this form of hyperphenylalaninemia may have a deficiency of tyrosine (which is created from
phenylalanine by PAH). These patients must be supplemented with tyrosine to account for this deficiency.
Dihydrobiopterin reductase activity is needed to replenish quinonoid-dihydrobiopterin back into its
tetrahydrobiopterin form, which is an important cofactor in many reactions in amino acid metabolism. Those
with this deficiency may produce sufficient levels of the enzyme phenylalanine hydroxylase (PAH) but,
since tetrahydrobiopterin is a cofactor for PAH activity, deficient dihydrobiopterin reductase renders any
PAH produced unable to use phenylalanine to produce tyrosine. Tetrahydrobiopterin is a cofactor in the
production of L-DOPA from tyrosine and 5-hydroxy-L-tryptophan from tryptophan, which must be
supplemented as treatment in addition to the supplements for classical PKU.
Levels of dopamine can be used to distinguish between these two types. Tetrahydrobiopterin is required to
convert Phe to Tyr and is required to convert Tyr to L-DOPA via the enzyme tyrosine hydroxylase. L-
DOPA, in turn, is converted to dopamine. Low levels of dopamine lead to high levels of prolactin. By
contrast, in classical PKU (without dihydrobiopterin involvement), prolactin levels would be relatively
normal.
Tetrahydrobiopterin deficiency can be caused by defects in four genes. They are known as HPABH4A,
HPABH4B, HPABH4C, and HPABH4D.[23]
Metabolic pathways[edit]
Pathophysiology of phenylketonuria, which is due to the absence of functional phenylalanine hydroxylase (classical subtype) or
functional enzymes for the recycling of tetrahydrobiopterin (new variant subtype) utilized in the first step of the metabolic
pathway.
The enzyme phenylalanine hydroxylase normally converts the amino acid phenylalanine into the amino

acid tyrosine. If this reaction does not take place, phenylalanine accumulates and tyrosine is deficient.
Excessive phenylalanine can be metabolized into phenylketones through the minor route,
a transaminase pathway with glutamate. Metabolites
include phenylacetate, phenylpyruvate and phenethylamine.[24] Elevated levels of phenylalanine in the blood
and detection of phenylketones in the urine is diagnostic, however most patients are diagnosed via
newborn screening.
Screening[edit]
Blood is taken from a two-week-old baby to test for phenylketonuria
PKU is commonly included in the newborn screening panel of many countries, with varied detection
techniques. Most babies in developed countries are screened for PKU soon after birth. [25] Screening for
PKU is done with bacterial inhibition assay (Guthrie test), immunoassays using fluorometric or photometric
detection, or amino acid measurement using tandem mass spectrometry (MS/MS). Measurements done
using MS/MS determine the concentration of Phe and the ratio of Phe to tyrosine, the ratio will be elevated
in PKU.[26]
Treatment[edit]
PKU is not curable. However, if PKU is diagnosed early enough, an affected newborn can grow up with
normal brain development by managing and controlling phenylalanine ("Phe") levels through diet, or a
combination of diet and medication.
Diet[edit]
People who follow the prescribed dietary treatment from birth, may have no symptoms. Their PKU would
be detectable only by a blood test. People must adhere to a special diet low in Phe for optimal brain
development. Since Phe is necessary for the synthesis of many proteins, it is required for appropriate
growth, but levels must be strictly controlled.
Optimal health ranges (or "target ranges") are between 120 and 360 µmol/L or equivalently 2 to 6 mg/dL,
and aimed to be achieved during at least the first 10 years, [27] to allow the brain to develop normally.
In the past, PKU-affected people were allowed to go off diet after approximately eight, then 18 years of
age. Today, most physicians recommend low Phe levels throughout life. For adults, somewhat higher
levels of Phe may be tolerable, but restriction is still advised to prevent mood disorders and difficulty
concentrating, among other neurological problems.[28]
The diet requires restricting or eliminating foods high in Phe, such as soybeans, seal meat, egg
whites, shrimps, chicken
breast, spirulina, watercress, fish, whale, nuts, crayfish,lobster, tuna, turkey, legumes, and lowfat cottage
cheese.[29] Starchy foods, such as potatoes and corn are generally acceptable in controlled amounts, but
the quantity of Phe consumed from these foods must be monitored. A food diary is usually kept to record
the amount of Phe consumed with each meal, snack, or drink. An "exchange" system can be used to
calculate the amount of Phe in a food from the protein content identified on a nutritional information label.
Lower-protein "medical food" substitutes are often used in place of normal bread, pasta, and other grain-
based foods, which contain a significant amount of Phe. Many fruits and vegetables are lower in Phe and
can be eaten in larger quantities. Infants may still be breastfed to provide all of the benefits of breastmilk,
but the quantity must also be monitored and supplementation for missing nutrients will be required. The
sweetener aspartame, present in many diet foods and soft drinks, must also be avoided, as aspartame
contains phenylalanine.
Different people can tolerate different amounts of Phe in their diet. Regular blood tests are used to
determine the effects of dietary Phe intake on blood Phe level.
Supplements[edit]
Supplementary "protein substitute" formulas are typically prescribed for people PKU (starting in infancy) to
provide the amino acids and other necessary nutrients that would otherwise be lacking in a low-
phenylalanine diet. Tyrosine, which is normally derived from phenylalanine and which is necessary for
normal brain function, is usually supplemented. Consumption of the protein substitute formulas can actually
reduce phenylalanine levels, probably because it stops the process of protein catabolism from releasing
Phe stored in the muscles and other tissues into the blood. Many PKU patients have their highest Phe
levels after a period of fasting (such as overnight), because fasting triggers catabolism. [30]A diet that is low in
phenylalanine but does not include protein substitutes may also fail to lower blood Phe levels, since a
nutritionally insufficient diet may also trigger catabolism. For all these reasons, the prescription formula is
an important part of the treatment for patients with classic PKU.
The oral administration of tetrahydrobiopterin (or BH4) (a cofactor for the oxidation of phenylalanine) can
reduce blood levels of this amino acid in some people.[31][32] Most people; however, have little or no benefit. [7]
Tentative evidence supports dietary supplementation with large neutral amino acids(LNAAs).[33] The LNAAs
(e.g. leu, tyr, trp, met, his, ile, val, thr) may compete with phe for specific carrier proteins that transport
LNAAs across the intestinal mucosa into the blood and across the blood brain barrier into the brain. It use
is really only indicated in adults who will not follow an appropriate diet. [2]
Another interesting treatment strategy for is casein glycomacropeptide (CGMP), which is a milk peptide
naturally free of Phe in its pure form[34] CGMP can substitute the main part of the free amino acids in the
PKU diet and provides several beneficial nutritional effects compared to free amino acids. The fact that
CGMP is a peptide ensures that the absorption rate of its amino acids is prolonged compared to free amino
acids and thereby results in improved protein retention [35] and increased satiety[36] compared to free amino
acids. Another important benefit of CGMP is that the taste is significantly improved [35] when CGMP
substitutes part of the free amino acids and this may help ensure improved compliance to the PKU diet.
Furthermore, CGMP contains a high amount of the phe lowering LNAAs, which constitutes about 41 g per
100 g protein[34] and will therefore help maintain plasma phe levels in the target range.
Women[edit]
For women with phenylketonuria, it is important for the health of their children to maintain low Phe levels
before and during pregnancy.[37] Though the developing fetus may only be a carrier of the PKU gene, the
intrauterine environment can have very high levels of phenylalanine, which can cross the placenta. The
child may develop congenital heart disease, growth retardation, microcephaly and intellectual disability as a
result.[38] PKU-affected women themselves are not at risk of additional complications during pregnancy.
In most countries, women with PKU who wish to have children are advised to lower their blood Phe levels
(typically to between 2 and 6 mg/dL) before they become pregnant, and carefully control their levels
throughout the pregnancy. This is achieved by performing regular blood tests and adhering very strictly to a
diet, in general monitored on a day-to-day basis by a specialist metabolic dietitian. In many cases, as the
fetus' liver begins to develop and produce PAH normally, the mother's blood Phe levels will drop, requiring
an increased intake to remain within the safe range of 2–6 mg/dL. The mother's daily Phe intake may
double or even triple by the end of the pregnancy, as a result. When maternal blood Phe levels fall below
2 mg/dL, anecdotal reports indicate that the mothers may suffer adverse effects, including headaches,
nausea, hair loss, and general malaise. When low phenylalanine levels are maintained for the duration of
pregnancy, there are no elevated levels of risk of birth defects compared with a baby born to a non-PKU
mother.[39]
Epidemiology[edit]
Country Incidence of PKU
Australia 1 in 10,000[40]
Canada 1 in 22,000[40]
China 1 in 17,000[40]
Czechoslovakia 1 in 7,000[40]
Denmark 1 in 12,000[40]
Finland 1 in 200,000[40]
France 1 in 13,500[40]
India 1 in 18,300
Ireland 1 in 4,500[41]
Italy 1 in 17,000[40]
Japan 1 in 125,000[40]
Korea 1 in 41,000[42]
Norway 1 in 14,500[40]
Turkey 1 in 2,600[40]
Philippines 1 in 102,000[43]
Scotland 1 in 5,300[40]
United
1 in 14,300[40]
Kingdom
United States 1 in 15,000[44]
The average number of new cases of PKU varies in different human populations. United States
Caucasians are affected at a rate of 1 in 10,000. [45] Turkey has the highest documented rate in the world,
with 1 in 2,600 births, while countries such as Finland and Japan have extremely low rates with fewer than
one case of PKU in 100,000 births. A 1987 study from Slovakia reports a Roma population with an
extremely high incidence of PKU (one case in 40 births) due to extensive inbreeding. [46] It is the most
common amino acid metabolic problem in the United Kingdom. [citation needed]
History[edit]
Before the causes of PKU were understood, PKU caused severe disability in most people who inherited the
relevant mutations. Nobel and Pulitzer Prize winning author Pearl S. Buck had a daughter named Carol
who lived with PKU before treatment was available, and wrote a moving account of its effects in a book
called The Child Who Never Grew.[47] Many untreated PKU patients born before widespread newborn
screening are still alive, largely in dependent living homes/institutions. [48]
Phenylketonuria was discovered by the Norwegian physician Ivar Asbjørn Følling in 1934[49] when he
noticed hyperphenylalaninemia (HPA) was associated with intellectual disability. In Norway, this disorder is
known as Følling's disease, named after its discoverer. [50]Følling was one of the first physicians to apply
detailed chemical analysis to the study of disease.
In 1934 at Rikshospitalet, Følling saw a young woman named Borgny Egeland. She had two children, Liv
and Dag, who had been normal at birth but subsequently developed intellectual disability. When Dag was
about a year old, the mother noticed a strong smell to his urine. Følling obtained urine samples from the
children and, after many tests, he found that the substance causing the odor in the urine was phenylpyruvic
acid. The children, he concluded, had excess phenylpyruvic acid in the urine, the condition which came to
be called phenylketonuria (PKU).[11]
His careful analysis of the urine of the two affected siblings led him to request many physicians near Oslo
to test the urine of other affected patients. This led to the discovery of the same substance he had found in
eight other patients. He conducted tests and found reactions that gave rise to benzaldehyde and benzoic
acid, which led him to conclude that the compound contained a benzene ring. Further testing showed
the melting point to be the same as phenylpyruvic acid, which indicated that the substance was in the urine.
His careful science inspired many to pursue similar meticulous and painstaking research with other
disorders.[citation needed]
PKU was the first disorder to be routinely diagnosed through widespread newborn screening. Robert
Guthrie introduced the newborn screening test for PKU in the early 1960s. [51]With the knowledge that PKU
could be detected before symptoms were evident, and treatment initiated, screening was quickly adopted
around the world. Austria started screening for PKU in 1966 [52] and England in 1968.[53]
Etymology and pronunciation[edit]

The word phenylketonuria uses combining forms of phenyl + ketone + -uria; it is pronounced /ˌfiːnaɪlˌkiːtə
ˈnjʊəriə, ˌfɛ-, -nɪl-, -nəl-, -toʊ-/[54][55].
Research[edit]
Other therapies are currently under investigation, including gene therapy.
Biomarin is currently conducting clinical trials to investigate PEG-PAL (PEGylated
recombinant phenylalanine ammonia lyase or ‘PAL’) is an enzyme substitution therapy in which the missing
PAH enzyme is replaced with an analogous enzyme that also breaks down Phe. PEG-PAL is now in Phase
2 clinical development.[56]
See also[edit]
 Hyperphenylalanemia
 Lofenalac
 Tetrahydrobiopterin deficiency
 Flowers for Algernon, which features a character who has
phenylketonuria
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42. Jump up^ Lee DH, Koo SK, Lee KS, Yeon YJ, Oh HJ, Kim SW, Lee
SJ, Kim SS, Lee JE, Jo I, Jung SC (2004). "The molecular basis of
phenylketonuria in Koreans". Journal of Human Genetics. 49 (1):
617–621. doi:10.1007/s10038-004-0197-5. PMID 15503242.
43. Jump up^ "Philippine Society for Orphan Disorders – Current
Registry". psod.org.ph.
44. Jump up^ Phenylketonuria at eMedicine
45. Jump up^ Bickel, H.; Bachmann, C.; Beckers, R.; Brandt, N.J.;
Clayton, B.E.; Corrado, G; et al. (1981). "Neonatal mass screening for
metabolic disorders: summary of recent sessions of the committee of
experts to study inborn metabolic diseases". public health committee,
Eur. J. Pediatr. (137): 133–139. doi:10.1007/BF00441305.
46. Jump up^ Ferák V, Siváková D, Sieglová Z (1987). "Slovenskí Cigáni
(Rómovia) – populácia s najvyšším koeficientom inbrídingu v
Európe.". Bratislavské lekárske listy (Bratislava Medical
Journal). 87 (2): 168–175.
47. Jump up^ Lee, Kathleen M.; Lee, Robert E. (December 1993). "The
child who never grew".American Journal of Human Genetics. 53 (6):
1370–1. PMC 1682478 .
48. Jump up^ "NPKUA > Education > About PKU". npkua.org.
49. Jump up^ Fölling, Asbjörn (1 January 1934). "Über Ausscheidung
von Phenylbrenztraubensäure in den Harn als Stoffwechselanomalie
in Verbindung mit Imbezillität.". Hoppe-Seyler´s Zeitschrift für
physiologische Chemie. 227 (1–4): 169–
181.doi:10.1515/bchm2.1934.227.1-4.169.
50. Jump up^ Centerwall SA, Centerwall WR (2000). "The discovery of
phenylketonuria: the story of a young couple, two affected children,
and a scientist". Pediatrics. 105 (1 Pt 1): 89–
103.doi:10.1542/peds.105.1.89. PMID 10617710.
51. Jump up^ Mitchell JJ, Trakadis YJ, Scriver CR (2011).
"Phenylalanine hydroxylase deficiency".Genetics in Medicine. 13 (8):
697–707. doi:10.1097/GIM.0b013e3182141b48.PMID 21555948.
52. Jump up^ Kasper DC, Ratschmann R, Metz TF, Mechtler TP,
Möslinger D, Konstantopoulou V, Item CB, Pollak A, Herkner KR
(2010). "The National Austrian Newborn Screening Program – Eight
years experience with mass spectrometry. Past, present, and future
goals". Wiener klinische Wochenschrift. 122 (21–22): 607–
613. doi:10.1007/s00508-010-1457-3. PMID 20938748.
53. Jump up^ Komrower GM, Sardharwalla IB, Fowler B, Bridge C
(1979). "The Manchester regional screening programme: A 10-year
exercise in patient and family care". British Medical Journal. 2 (6191):
635–638. doi:10.1136/bmj.2.6191.635. PMC 1596331
.PMID 497752.
54. Jump up^ "Phenylketonuria". Merriam-Webster Dictionary.
55. Jump up^ "Phenylketonuria". Oxford Dictionaries. Oxford University
Press. Retrieved2016-01-20.
56. Jump up^ "BioMarin : Pipeline : Pipeline Overview : BMN 165 for
PKU". bmrn.com.
 Phenylketonuria at DMOZ
[hide]
Inborn error of amino acid metabolism (E70–E72, 270)
Glutaric acidemia type 1
type 2
Lysine/straight chain Hyperlysinemia
Pipecolic acidemia
Saccharopinuria
3-hydroxy-3-methylglutaryl-CoA lyase deficiency
3-Methylcrotonyl-CoA carboxylase deficiency
Leucine 3-Methylglutaconic aciduria 1
Isovaleric acidemia
Maple syrup urine disease

Tryptophan Hypertryptophanemia
D-Glyceric acidemia
Glutathione synthetase deficiency
G→pyruvate→citrate Glycine Sarcosinemia
Glycine→Creatine: GAMT deficiency
Glycine encephalopathy
Carnosinemia
Histidine Histidinemia
Urocanic aciduria
G→glutamate→
α-ketoglutarate Hyperprolinemia
Proline
Prolidase deficiency
Glutamate/glutamine SSADHD
Hypervalinemia
Valine Isobutyryl-CoA dehydrogenase deficiency
2-Methylbutyryl-CoA dehydrogenase deficiency
Isoleucine Beta-ketothiolase deficiency
G→propionyl-CoA→ Maple syrup urine disease
succinyl-CoA Cystathioninuria
Methionine Homocystinuria
Hypermethioninemia
Methylmalonic acidemia
General BC/OA Methylmalonyl-CoA mutase deficiency
Propionic acidemia
G→fumarate Phenylalanine/tyrosine 6-Pyruvoyltetrahydropterin synthase deficiency

Phenylketonuria
Tetrahydrobiopterin deficiency
Alkaptonuria/Ochronosis
Type I tyrosinemia
Tyrosinemia
Type II tyrosinemia
Type III tyrosinemia/Hawkinsinuria
Tyrosine→Melanin Albinism: Ocular albinism (1)

Oculocutaneous albinism (Hermansky–Pudlak syndrome)
Waardenburg syndrome
Dopamine beta hydroxylase deficiency

Tyrosine→Norepinephrine
reverse: Brunner syndrome
Argininemia
Argininosuccinic aciduria
Urea cycle/Hyperammonemia
Carbamoyl phosphate synthetase I deficiency
G→oxaloacetate (arginine
Citrullinemia
 aspartate)
N-Acetylglutamate synthase deficiency
Ornithine transcarbamylase deficiency/translocase deficiency
Solute carrier family: Cystinuria
Hartnup disease
Iminoglycinuria
Lysinuric protein intolerance
Fanconi syndrome: Oculocerebrorenal syndrome
Cystinosis
2-Hydroxyglutaric aciduria
Aminoacylase 1 deficiency
Ethylmalonic encephalopathy
Fumarase deficiency
Trimethylaminuria
Categories:
 Intellectual disability
 Autosomal recessive disorders
 Amino acid metabolism disorders
 Skin conditions resulting from errors in metabolism
 Disorders causing seizures
 Biology of attention deficit hyperactivity disorder
 Rare diseases
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Alkaptonuria
Alkaptonuria
Pigmentation of the face in alkaptonuria
Specialty endocrinology
ICD-10 E70.2 (ILDS E70.210)
ICD-9-CM 270.2
OMIM 203500
DiseasesDB 409
MedlinePlus 001200
eMedicine ped/64
Patient UK Alkaptonuria
MeSH D000474
Alkaptonuria
GeneReviews
[edit on Wikidata]
Alkaptonuria (black urine disease, black bone disease, or alcaptonuria) is a rare inherited genetic

disorder in which the body cannot process the amino acids phenylalanine and tyrosine, which occur in
protein. It is caused by a mutation in the HGD gene for the enzyme homogentisate 1,2-
dioxygenase (EC 1.13.11.5); if a person inherits abnormal copies from each parent (it is a recessive
condition) the body accumulates an intermediate substance called homogentisic acid in the blood and
tissues. Homogentisic acid and its oxidated form alkapton are excreted in the urine, giving it an unusually
dark color. The accumulating homogentisic acid causes damage to cartilage (ochronosis, leading
to osteoarthritis) and heart valves as well as precipitating as kidney stones and stones in other organs.
Symptoms usually develop in people over thirty years old, although the dark discoloration of the urine is
present from birth.
Apart from treatment of the complications (such as pain relief and joint replacement for the cartilage
damage), vitamin C has been used to reduce the ochronosis and lowering of the homogentisic acid levels
may be attempted with a low-protein diet. Recently the drug nitisinone has been found to suppresses
homogentisic acid production, and research is ongoing as to whether it can improve symptoms.
Alkaptonuria is a rare disease; it occurs in one in 250,000 people, but is more common in Slovakia and
the Dominican Republic.
Contents
[hide]

 3Diagnosis
 4Treatment
 5Prognosis
 6Epidemiology
 7History
 8Research directions
 9See also
 10References
Intervertebral discs calcification due to ochronosis
Patients with alkaptonuria are asymptomatic as children or young adults, but their urine may turn brown or
even inky black if collected and left exposed to open air. [1] Pigmentation may be noted in the cartilage of the
ear as well as other cartilage,[1][2] and the sclera and corneal limbus of the eye.[3]
After the age of thirty people begin to develop pain in the weight-bearing joints of the spine, hips and
knees. The pain can be severe to the point that interferes with activities of daily living and may affect ability
to work. Joint replacement surgery (hip and shoulder) is often necessary at a relatively young age. [1] In the
longer term, the involvement of the spinal joints leads to reduced movement of the rib cage and can affect
breathing.[1] Bone mineral density may be affected, increasing the risk of bone fractures, and rupture of
tendons and muscles may occur.[1]
Valvular heart disease, mainly calcification and regurgitation of the aortic and mitral valves, may occur, and
in severe and progressive cases valve replacement may be necessary. Irregularities in the heart
rhythm and heart failure affect a significant proportion of people with alkaptonuria (40% and 10%
respectively).[1] Hearing loss affects 40% of people. There is also a propensity to developing kidney stones,
and eventually also gallstones and stones in the prostate and salivary glands (sialolithiasis).[1]
Chemical skeletal formula of homogentisic acid, which accumulates in the body fluids of people with alkaptonuria.
Every person carries in their DNA two copies (one received from each parent) of the gene HGD, which
contains the genetic information to produce the enzyme homogentisate 1,2-dioxygenase (HGD) which can
normally be found in numerous tissues in the body (liver, kidney, small intestine, colon and prostate). In
people with alkaptonuria, both copies of the gene contain abnormalities that mean that the body cannot
produce an adequately functioning enzyme.[4] HGD mutations are generally found in certain parts (exons 6,
8, 10 and 13) but a total of over 100 abnormalities have been described throughout the gene. [4] The normal
HGD enzyme is a hexamer (it has six subunits) that are organized in two groups of three (two trimers) and
contains an iron atom. Different mutations may affect the structure, function or solubility of the enzyme.
[4]
Very occasionally the disease appears to be transmitted in an autosomal dominant fashion, where a
single abnormal copy of HGD from a single parent is associated with alkaptonuria; it is possible that other
mechanisms or defects in other genes are responsible in those cases. [4]
Pathophysiology of alkaptonuria, which is due to the absence of functional homogentisate dioxygenase in the liver.
The HGD enzyme in involved in the metabolism (chemical processing) of the aromatic amino
acids phenylalanine and tyrosine. Normally these enter the bloodstream through protein-containing food
and the natural turnover of protein in the body. Tyrosine is specifically required for a number of functions
such as hormones (e.g. thyroxine, the thyroid hormone), melanin (the dark pigment in the skin and hair)
and certain proteins, but the vast majority (over 95%) is unused and is metabolized through a group of
enzymes that eventually generate acetoacetate and malate.[1] In alkaptonuria the HGD enzyme cannot
metabolize the homogentisic acid (generated from tyrosine) into 4-maleylacetoacetate, and homogentisic
acid levels in the blood are a hundredfold higher than would normally be expected, despite the fact that a
substantial amount is eliminated into the urine by the kidneys.[1]
The homogentisic acid is converted to the related substance benzoquinone acetic acid (BQA) which
forms polymers that resemble the skin pigment melanin. These are deposited in the collagen, a connective
tissue protein, of particular tissues such as cartilage. This process is called ochronosis (as the tissue
looks ochre); ochronotic tissue is stiffened and unusually brittle, impairing its normal function and causing
damage.[1]
Diagnosis[edit]
Urine of a four-month-old baby with dark urine (on the left) after 10% ammonia and 3% silver nitrate were added. The tube in
the middle is a normal control. Color change on alkalinization is not a specific test, and confirmatory investigations are needed.
[1]
If the diagnosis of alkaptonuria is suspected, this can be confirmed or excluded by collecting urine for
twenty-four hours and determining the amount of homogentisic acid by means of chromatography. There is
no validated assay of HGA in blood.[1]
The severity of the symptoms and response to treatment can be quantified through a validated
questionnaire titled the AKU Severity Score Index. This includes assigns scores to the presence of
particular symptoms and features, such as the presence of eye and skin pigmentation, joint pain, heart
problems and organ stones.[1]
Treatment[edit]
No treatment modality has been unequivocally demonstrated to reduce the complications of alkaptonuria.
Main treatment attempts have focused on preventing ochronosis through the reduction of accumulating
homogentisic acid. Such commonly recommended treatments include large doses of ascorbic acid (vitamin
C) or dietary restriction of amino acids phenylalanine and tyrosine. However, vitamin C treatment has not
shown to be effective,[1] and protein restriction (which can be difficult to adhere to) has not shown to be
effective in clinical studies.[1]
Several recent studies have suggested that the herbicide nitisinone may be effective in the treatment of
alkaptonuria. Nitrisinone inhibits the enzyme, 4-hydroxyphenylpyruvate dioxygenase, responsible for
converting tyrosine to homogentisic acid, thereby blocking the production and accumulation of HGA.
Nitisinone has been used for some time at much higher doses in the treatment of type I tyrosinemia.
Nitisinone treatment has been shown to cause a larger than 95% reduction in plasma and urinary HGA.
[1]
The main drawback is accumulation of tyrosine, the long-term risks of which are unknown; there is a
particular concern about damage to the cornea of the eye. Long-term use would require frequent
monitoring for complications.[1]
Prognosis[edit]
Alkaptonuria does not appear to affect life expectancy, although this has not been surveyed in the last 40
years.[1] The main impact is on quality of life; many people with alkaptonuria have disabling symptoms such
as pain, poor sleep and breathing symptoms. These generally start in the fourth decade. The average age
at requiring joint replacement surgery is 50–55 years. [1]
Epidemiology[edit]
In most ethnic groups, the prevalence of alkaptonuria is between 1:100,000 and 1:250,000. [4] In Slovakia
and the Dominican Republic the disease is much more common, with prevalence estimated at 1:19,000
people.[4] As for Slovakia, this is not the result of a single mutation but due to a group of 12 mutations in
specific "hot spots" of the HGD gene.[4]The Slovakian clustering probably arose in a small area in the
northwest of the country and spread after the 1950s due to migration. [4]
History[edit]
Alkaptonuria was one of the four diseases described by Sir Archibald Edward Garrod, as being the result of
the accumulation of intermediates due to metabolic deficiencies. He linked ochronosis with the
accumulation of alkaptans in 1902,[4][5] and his views on the subject, including its mode of heritance, were
summarized in a 1908 Croonian Lecture at theRoyal College of Physicians.[4][6][7]
The defect was narrowed down to homogentisic acid oxidase deficiency in a study published in 1958. [4]
[8]
The genetic basis was elucidated in 1996, when HGD mutations were demonstrated. [4][9]
A 1977 study showed that an ochronotic Egyptian mummy had probably suffered from alkaptonuria.[10][11]
Research directions[edit]
Research collaborations by several national centres have been established to find a more definitive
treatment for alkaptonuria. This has included studies on the use of nitisinone and investigations into
antioxidants to inhibit ochronosis.[4] The ideal treatment would replace HGD enzyme function without
accumulating other substances.[1]
See also[edit]
 Ochronosis
 List of cutaneous conditions
 List of radiographic findings associated with cutaneous conditions
References[edit]
1. ^ Jump up to: Ranganath LR, Jarvis JC, Gallagher
a b c d e f g h i j k l m n o p q r s t
JA (May 2013). "Recent advances in management of alkaptonuria

(invited review; best practice article)".J. Clin. Pathol. 66 (5): 367–
73. doi:10.1136/jclinpath-2012-200877. PMID 23486607.
2. Jump up^ Speeckaert R, Van Gele M, Speeckaert MM, Lambert J,
van Geel N (July 2014). "The biology of hyperpigmentation
syndromes". Pigment Cell Melanoma Res. 27 (4): 512–
24. doi:10.1111/pcmr.12235. PMID 24612852.
3. Jump up^ Lindner, Moritz; Bertelmann, Thomas (2014-01-30). "On
the ocular findings in ochronosis: a systematic review of
literature". BMC Ophthalmology. 14 (1): 12.doi:10.1186/1471-2415-
14-12. ISSN 1471-2415. PMC 3915032 . PMID 24479547.
4. ^ Jump up to: Zatkova A (December 2011). "An update on
a b c d e f g h i j k l m
molecular genetics of Alkaptonuria (AKU)". J. Inherit. Metab.

Dis. 34 (6): 1127–36. doi:10.1007/s10545-011-9363-
z. PMID 21720873.
5. Jump up^ Garrod AE (1902). "The incidence of alkaptonuria: a study
in clinical individuality".Lancet. 2 (4137): 1616–
1620. doi:10.1016/S0140-6736(01)41972-6. Reproduced inGarrod AE
(2002). "The incidence of alkaptonuria: a study in chemical
individuality. 1902 classical article". Yale Journal of Biology and
Medicine. 75 (4): 221–31. PMC 2588790 . PMID 12784973.
6. Jump up^ Garrod AE (1908). "The Croonian lectures on inborn errors
of metabolism: lecture II: alkaptonuria". Lancet. 2: 73–
79. doi:10.1016/s0140-6736(01)78041-5.
7. Jump up^ Garrod AE (1909). "Inborn errors of metabolism". Oxford
University Press.OL 7116744M.
8. Jump up^ La Du BN, Zannoni VG, Laster L, Seegmiller JE (1
January 1958). "The nature of the defect in tyrosine metabolism in
alcaptonuria" (PDF). Journal of Biological Chemistry.230 (1): 251–
60. PMID 13502394.
9. Jump up^ Fernández-Cañón JM, Granadino B, Beltrán-Valero de
Bernabé D, et al. (1996). "The molecular basis of
alkaptonuria". Nature Genetics. 14 (1): 19–24. doi:10.1038/ng0996-
19. PMID 8782815.
10. Jump up^ Stenn FF, Milgram JW, Lee SL, Weigand RJ, Veis A
(1977). "Biochemical identification of homogentisic acid pigment in an
ochronotic egyptian mummy". Science.197 (4303): 566–
8. doi:10.1126/science.327549. PMID 327549.
11. Jump up^ Lee, SL.; Stenn, FF. (Jul 1978). "Characterization of
mummy bone ochronotic pigment.". JAMA. 240 (2): 136–
8. doi:10.1001/jama.1978.03290020058024.PMID 351220.
 AKU Society (UK)
 DevelopAKUre clinical trials
 AKU and chromosome 3, Royal Institution video
[hide]
type 2
Pipecolic acidemia
Saccharopinuria
Isovaleric acidemia
D-Glyceric acidemia
G→glutamate→ Histidine Carnosinemia
α-ketoglutarate Histidinemia
Urocanic aciduria
Hyperprolinemia
Proline
Hypervalinemia
2-Methylbutyryl-CoA dehydrogenase deficiency
G→propionyl-CoA→ Maple syrup urine disease
succinyl-CoA Cystathioninuria
Hypermethioninemia
Propionic acidemia
6-Pyruvoyltetrahydropterin synthase deficiency

Phenylketonuria
Type I tyrosinemia
Tyrosinemia
Type II tyrosinemia
G→fumarate Phenylalanine/tyrosine Type III tyrosinemia/Hawkinsinuria
Albinism: Ocular albinism (1)
Tyrosine→Melanin Oculocutaneous albinism (Hermansky–Pudlak syndrome)

Urea cycle/Hyperammonemia Argininemia
(arginine Argininosuccinic aciduria

G→oxaloacetate
 aspartate) Carbamoyl phosphate synthetase I deficiency
Citrullinemia
Hartnup disease
Iminoglycinuria
Cystinosis
Fumarase deficiency
Trimethylaminuria
Categories:
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

Albinism
"Albino" redirects here. For an overview, see Albinism in biology. For other uses, see Albino
(disambiguation).
Albinism
achromia, achromasia, achromatosis
A boy of Black ethnicity with albinism
Pron albino (UK /ælˈbiːnoʊ/,[1]US /ælˈbaɪnoʊ/)[2]
uncia
tion
Speci Dermatology
alty
ICD- E70.3
10
ICD- 270.2
9-
CM
OMI 203100 103470, 203200,606952, 203290, 203300, 203310,256710, 2784
M 00, 214450, 214500,220900, 300500, 300600, 300650,300700, 600501,
604228, 606574,606952, 607624, 609227
Disea 318
sesD
Medl 001479
inePl
us
eMed derm/12
icine
Patie Albinism
nt
UK
MeS D000417
[edit on Wikidata]
Albinism in humans is a congenital disorder characterized by the complete or partial absence

of pigment in the skin, hair and eyes. Albinism is associated with a number of vision defects, such
as photophobia, nystagmus, and amblyopia. Lack of skin pigmentation makes for more susceptibility to
sunburn and skin cancers. In rare cases such as Chédiak–Higashi syndrome, albinism may be associated
with deficiencies in the transportation of melanin granules. This also affects essential granules present in
immune cells leading to increased susceptibility to infection. [3]
Albinism results from inheritance of recessive gene alleles and is known to affect all vertebrates,

including humans. It is due to absence or defect of tyrosinase, a copper-containing enzyme involved in the
production of melanin. It is the opposite of melanism. Unlike humans, other animals have
multiple pigments and for these, albinism is considered to be a hereditary condition characterised by the
absence of melanin in particular, in the eyes, skin, hair, scales, feathers or cuticle. [4] While an organism with
complete absence of melanin is called an albino an organism with only a diminished amount of melanin is
described as leucistic or albinoid.[5] The term is from the Latin albus, "white".
Contents
[hide]

o 1.1Visual problems
 2Genetics
o 2.1Enzyme
o 2.2Evolutionary theories
 3Diagnosis
 4Treatment
 5Epidemiology
 6Society and culture
o 6.1International Albinism Awareness Day
 7Other organisms
 8See also
 9References
Signs and symptoms
Albino girl from Papua New Guinea
In humans, there are two principal types of albinism: oculocutaneous, affecting the eyes, skin and hair,
and ocular affecting the eyes only.
Most people with oculocutaneous albinism appear white or very pale, as the melanin pigments responsible
for brown, black, and some yellow colorations are not present. Ocular albinism results in light blue eyes,
[6]
and may require genetic testing to diagnose.
Because individuals with albinism have skin that entirely lacks the dark pigment melanin, which helps
protect the skin from the sun's ultraviolet radiation, their skin can burn more easily from overexposure.[7]
The human eye normally produces enough pigment to color the iris blue, green or brown and lend opacity
to the eye. In photographs, those with albinism are more likely to demonstrate "red eye," due to the red
of retina being visible through the iris. Lack of pigment in the eyes also results in problems with vision, both
related and unrelated to photosensitivity.
Those afflicted with albinism are generally as healthy as the rest of the population (but see related
disorders below), with growth and development occurring as normal, and albinism by itself does not cause
mortality,[8] although the lack of pigment blocking ultraviolet radiation increases the risk of melanomas (skin
cancers) and other problems.
Visual problems
Malian albino singer Salif Keita from Mandinka culture.
Development of the optical system is highly dependent on the presence of melanin, and the reduction or
absence of this pigment in sufferers of albinism may lead to:
 Misrouting of the retinogeniculate projections, resulting in

abnormal decussation (crossing) of optic nerve fibres[7]
 Photophobia and decreased visual acuity due to light scattering within
the eye (ocular straylight)[7][9]
 Reduced visual acuity due to foveal hypoplasia and possibly light-
induced retinal damage.[7]
Eye conditions common in albinism include:
 Nystagmus, irregular rapid movement of the eyes back and forth, or in

circular motion.[7]
 Amblyopia, decrease in acuity of one or both eyes due to poor
transmission to the brain, often due to other conditions such
as strabismus.[7]
 Optic nerve hypoplasia, underdevelopment of the optic nerve.
The improper development of the retinal pigment epithelium (RPE), which in normal eyes absorbs most of
the reflected sunlight, further increases glare due to light scattering within the eye. [10] The resulting
sensitivity (photophobia) generally leads to discomfort in bright light, but this can be reduced by the use of
sunglasses and/or brimmed hats.[11]
Genetics
Oculocutaneous albinism is generally the result of the biological inheritance of genetically
recessive alleles (genes) passed from both parents of an individual for example OCA1and OCA2. A
mutation in the human TRP-1 gene may result in the deregulation of melanocyte tyrosinase enzymes, a
change that is hypothesized to promote brown versus black melanin synthesis, resulting in a third
oculocutaneous albinism (OCA) genotype, ″OCA3″. [12] Some rare forms are inherited from only one parent.
There are other genetic mutations which are proven to be associated with albinism. All alterations,
however, lead to changes in melanin production in the body. [8][13] Some of these are associated with
increased risk of skin cancer (see list of such genetic variations).
The chance of offspring with albinism resulting from the pairing of an organism with albinism and one
without albinism is low. However, because organisms (including humans) can be carriers of genes for
albinism without exhibiting any traits, albinistic offspring can be produced by two non-albinistic parents.
Albinism usually occurs with equal frequency in both sexes.[8] An exception to this is ocular albinism, which
it is passed on to offspring through X-linked inheritance. Thus, ocular albinism occurs more frequently in
males as they have a single X and Y chromosome, unlike females, whose genetics are characterized by
two X chromosomes.[14]
There are two different forms of albinism: a partial lack of the melanin is known as hypomelanism, or
hypomelanosis, and the total absence of melanin is known as amelanism or amelanosis.
Enzyme
The enzyme defect responsible for OCA1-type albinism is tyrosine 3-monooxygenase (tyrosinase), which
synthesizes melanin from the amino acid tyrosine.
Evolutionary theories
It is suggested that the early hominin evolved in East Africa around 3 million years ago.[15] The
dramatic phenotypic change from primate to early hominin is hypothesized to have involved the extreme
loss of body hair – except for areas most exposed to UV radiation, such as the head – to allow for more
efficient thermoregulation in the early hunter-gatherers. The skin that would have been exposed upon
general body hair loss in these early hominins would have most likely been non-pigmented, reflecting the
pale skin underlying the hair of our chimpanzee relatives. A positive advantage would have been conferred
to early hominids inhabiting the African continent that were capable of producing darker skin – those who
first expressed the eumelanin-producing MC1R allele – which protected them from harmful epithelium-
damaging ultraviolet rays. Over time, the advantage conferred to those with darker skin may have led to the
prevalence of darker skin on the continent. The positive advantage, however, would have had to be strong
enough so as to produce a significantly higher reproductive fitness in those who produced more melanin.
The cause of a selective pressure strong enough to cause this shift is an area of much debate. Some
hypotheses include the existence of significantly lower reproductive fitness in people with less melanin due
to lethal skin cancer, lethal kidney disease due excessvitamin D formation in the skin of people with less
melanin, or simply natural selection due to mate preference and sexual selection. [15]
When comparing the prevalence of albinism in Africa to its prevalence in other parts of the world, such as
Europe and the United States, the potential evolutionary effects of skin cancer as a selective force due to
its effect on these populations may not be insignificant. The prevalence of albinism in some ethnic
groups in sub-Saharan Africa is around 1 in 5,000, while in Europe and the US it is 1 in 20,000. [15] It would
follow, then, that there would be stronger selective forces acting on albino populations in Africa than on
albino populations in Europe and the US. Rates as high as 1 in 1,000 have been reported for some
populations in Zimbabwe and other parts of Southern Africa.[16] In two separate studies in Nigeria, people
suffering from albinism were found to be of reproductively significant age more often than not. One study
found that 89% of people diagnosed with albinism are between 0 and 30 years of age, while the other
found that 77% of albinos were under the age of 20.[16]
Diagnosis
This section needs additional citations for verification. Please help improve this article by adding
citations to reliable sources. Unsourced material may be challenged and removed. (November 2007) (Learn
how and when to remove this template message)
Genetic testing can confirm albinism and what variety it is, but offers no medical benefits except in the
cases of non-OCA disorders that cause albinism along with other medical problems which may be
treatable. There is no 'cure' for Albinism. The symptoms of albinism can be assisted by various methods.
Treatment
As there is no cure for albinism, it is managed through lifestyle adjustments. People with albinism need to
take care not to sunburn and should have regular healthy skin checks by a dermatologist.
For the most part, treatment of the eye conditions consists of visual rehabilitation. Surgery is possible on
the extra-ocular muscles to decrease strabismus.[7] Nystagmus-damping surgery can also be performed, to
reduce the "shaking" of the eyes back and forth. [17] The effectiveness of all these procedures varies greatly
and depends on individual circumstances.
Glasses and other vision aids, large-print materials as well as bright but angled reading lights, can help
individuals with albinism, even though their vision cannot be corrected completely. Some people with
albinism do well using bifocals (with a strong reading lens), prescription reading glasses, and/or hand-held
devices such as magnifiers ormonoculars.[11]
Albinism is often[dubious – discuss] associated with the absence of an iris in the eye. Contact lenses may be colored
to block light transmission through the aniridic eye. Some usebioptics, glasses which have small telescopes
mounted on, in, or behind their regular lenses, so that they can look through either the regular lens or the
telescope. Newer designs of bioptics use smaller light-weight lenses. Some US states allow the use of
bioptic telescopes for driving motor vehicles. (See also NOAH bulletin "Low Vision Aids".)
To support those with albinism, and their families, the National Organization for Albinism and
Hypopigmentation was set up to provide a network of resources and information.
Epidemiology
Albinism affects people of all ethnic backgrounds; its frequency worldwide is estimated to be approximately
one in 17,000. Prevalence of the different forms of albinism varies considerably by population, and is
highest overall in people of sub-Saharan African descent.[18]
Society and culture

Main articles: Persecution of people with albinism and Albinism in popular culture
In physical terms, humans with albinism commonly have visual problems and need sun protection. They
often face social and cultural challenges (even threats), as the condition is often a source of ridicule,
discrimination, or even fear and violence. It is especially socially deterring to African people. A study
conducted in Nigeria on albino children stated that "they experienced alienation, avoided social interactions
and were less emotionally stable. Furthermore, affected individuals were less likely to complete schooling,
find employment, and find partners".[19] Many cultures around the world have developed beliefs regarding
people with albinism.
In African countries such as Tanzania[20] and Burundi,[21][22] there has been an unprecedented rise
in witchcraft-related killings of people with albinism in recent years, because their body parts are used in
potions sold by witchdoctors.[23] Numerous authenticated incidents have occurred in Africa during the 21st
century.[24][25][26][27] For example, in Tanzania, in September 2009, three men were convicted of killing a 14-
year-old albino boy and severing his legs in order to sell them for witchcraft purposes. [28] Again in Tanzania
and Burundi in 2010, the murder and dismemberment of a kidnapped albino child was reported from the
courts,[21] as part of a continuing problem. National Geographic estimates that in Tanzania a complete set of
albino body parts is worth $75,000.[29]
Another harmful and false belief is that sex with an albinistic woman will cure a man of HIV. This has led,
for example in Zimbabwe, to rapes (and subsequent HIV infection).[30]
Certain ethnic groups and populations in isolated areas exhibit heightened susceptibility to albinism,
presumably due to genetic factors. These include notably the Native AmericanKuna, Zuni and Hopi nations
(respectively of Panama, New Mexico and Arizona); Japan, in which one particular form of albinism is
unusually common; and Ukerewe Island, the population of which shows a very high incidence of albinism. [31]
Famous people with albinism include historical figures such as Oxford don William Archibald Spooner;
actor-comedian Victor Varnado; musicians such as Johnny and Edgar Winter, Salif Keita, Winston
"Yellowman" Foster, Brother Ali, Sivuca, Willie "Piano Red" Perryman; and fashion models Connie
Chiu and Shaun Ross. Emperor Seinei of Japan is thought to have been an albino because he was said to
have been born with white hair.
International Albinism Awareness Day
International Albinism Awareness Day was established after a motion was accepted on the 18th of
December 2014 by the United Nations General Assembly, proclaiming that as of 2015 the 13th of June
would be known as International Albinism Awareness Day.[32] This was followed by a mandate created by
the United Nations Human Rights Council that appointed Ms. Ikponwosa Ero, who is from Nigeria, as the
very first Independent Expert on the enjoyment of human rights by persons with albinism. [33]
Other organisms
Corn plant with albinism
Main article: Albinism in biology

Albinism and other types of pigment mutations also occur in the animal and plant kingdoms.
See also
 Albinism–deafness syndrome
 Amelanism
 Dyschromia
 Erythrism, unusually red pigmentation
 Heterochromia iridum
 Human variability
 Isabellinism
 Leucism
 Melanism
 Nevus, or birthmark
 National Organization for Albinism and Hypopigmentation
 Piebaldism, patchy alternating loss of and concentrations of dermal
pigmentation
 Vitiligo (or leukoderma), patchy loss of dermal pigmentation
 Xanthochromism and axanthism, unusually yellow pigmentation and
lack of yellow pigment, respectively
References
1. Jump up^ "Albino" Dictionary.com. Accessed May 11, 2011
2. Jump up^ "Pronunciation of albino" Macmillan Dictionary. Accessed
May 11, 2011
3. Jump up^ Kaplan, J.; De Domenico, I.; Ward, D. M. (2008).
"Chediak-Higashi syndrome". Current Opinion in Hematology. 15 (1):
22–29. doi:10.1097/MOH.0b013e3282f2bcce.PMID 18043242.
4. Jump up^ "Albinism". Encyclopædia Britannica. Retrieved January
27, 2015.
5. Jump up^ Tietz, W. (1963). "A Syndrome of Deaf-Mutism Associated
with Albinism Showing Dominant Autosomal Inheritance". American
journal of human genetics. 15: 259–64.PMC 1932384
. PMID 13985019.
6. Jump up^ Wolf, Sebastian (2005). Ocular Fundus: From Findings to
Diagnosis. Thieme Medical Publishers. p. 96. ISBN 978-3131393715.
Retrieved 1 November 2014.
7. ^ Jump up to: Chen, Harold (2006). Atlas of genetic diagnosis and
a b c d e f g
counseling. Totowa, NJ: Humana Press. pp. 37–40. ISBN 1-58829-

681-4. Retrieved 22 July 2010.
8. ^ Jump up to: Boissy, Raymond E. et al. (22 August 2005) "Albinism",
a b c
at eMedicine. Retrieved 31 March 2007.

9. Jump up^ Kruijt, Bastiaan; Franssen, Luuk; Prick, Liesbeth J. J. M.;
Van Vliet, Johannes M. J.; Van Den Berg, Thomas J. T. P. (2011).
"Ocular Straylight in Albinism". Optometry and Vision Science. 88 (5):
E585. doi:10.1097/OPX.0b013e318212071e.PMID 21358444.
10. Jump up^ "Albinism" in Handbook of Ocular Disease Management
11. ^ Jump up to: King, Richard. "Facts about
a b
Albinism". albinism.med.umn.edu.
12. Jump up^ Boissy, R. E.; Zhao, H; Oetting, W. S.; Austin, L. M.;
Wildenberg, S. C.; Boissy, Y. L.; Zhao, Y; Sturm, R. A.; Hearing, V. J.;
King, R. A.; Nordlund, J. J. (1996). "Mutation in and lack of expression
of tyrosinase-related protein-1 (TRP-1) in melanocytes from an
individual with brown oculocutaneous albinism: A new subtype of
albinism classified as "OCA3"". American journal of human
genetics. 58 (6): 1145–56. PMC 1915069 .PMID 8651291.
13. Jump up^ Online Mendelian Inheritance in Man, at Johns Hopkins
University (see alsoMendelian Inheritance in Man for more information
about this source).
14. Jump up^ Haldeman-Englert, Chad. "Sex-linked recessive", Division
of Human Genetics, Children's Hospital of Philadelphia, Philadelphia,
PA
15. ^ Jump up to: Greaves M. (2014). "Was skin cancer a selective force
a b c
for black pigmentation in early hominin evolution?". Proceedings of

the Royal Society B: Biological Sciences. 281(1781):
20132955. doi:10.1098/rspb.2013.2955.
16. ^ Jump up to: Hong ES, Zeeb H, Repacholi MH (2006). "Albinism in
a b
Africa as a public health issue". BMC Public Health. 6:

212. doi:10.1186/1471-2458-6-212. PMC 1584235
.PMID 16916463.
17. Jump up^ Lee J (May 2002). "Surgical management of
nystagmus". Journal of the Royal Society of Medicine. 95 (5): 238–
41. doi:10.1258/jrsm.95.5.238. PMC 1279676 .PMID 11983764.
18. Jump up^ Gronskov K, Ek J, Brondum-Nielsen K (2 November
2007). "Oculocutaneous albinism". Orphanet Journal of Rare
Diseases. 2: 43. doi:10.1186/1750-1172-2-43.PMC 2211462
. PMID 17980020.
19. Jump up^ Magna, P (January 2014). "Biology and genetics of
Oculocutaneous albinism and vitiligo-common pigmentation disorders
in Southern Africa". SAMJ- South African Medical
Journal. 103 (1). PMID 24300644.
20. Jump up^ "Africa | Living in fear: Tanzania's albinos". BBC News.
2008-07-21. Retrieved27 February 2010.
21. ^ Jump up to: "Burundi albino boy 'dismembered'". BBC News. 24
a b
October 2010.
22. Jump up^ "Burundian albino murders denied". BBC News. 2009-05-
19. Retrieved 27 February2010.
23. Jump up^ Reportage "Zeru, Zeru: Being albino in
Tanzanie" by Franck Vogel inside Visura Magazine
24. Jump up^ "Man 'tried to sell' albino wife". BBC News. 2008-11-13.
25. Jump up^ "Tanzania albinos targeted again". BBC News. 2008-07-
26. Jump up^ Ntetema, Vicky (2008-07-24). "In hiding for exposing
Tanzania witchdoctors". BBC News. Retrieved 27 February 2010.
27. Jump up^ "Mothers hacked in albino attacks". BBC News. 2008-11-
28. Jump up^ "Death for Tanzania albino killers". BBC News. 2009-09-
29. Jump up^ "Pictures: Inside the Lives of Albinos in
Tanzania". National Geographic.
30. Jump up^ Machipisa, Lewis. "RIGHTS-ZIMBABWE: The Last
Minority Group to Find a Voice".Inter Press Service News Agency.
IPS-Inter Press Service. Retrieved 30 January 2010.
31. Jump up^ Anon (2009). "Ukerewe Albino Society". southern-africas-
children.org.uk/. Southern Africas Children. Retrieved 21 July 2010.
32. Jump up^ "International Albinism Awareness Day".
33. Jump up^ "Independent Expert on the enjoyment of human rights by
persons with albinism".
External links
media related to Albinism.
Look
up albinism or albinoin
Wiktionary, the free
dictionary.
 GeneReview/NCBI/NIH/UW entry on Oculocutaneous Albinism Type 2

 GeneReview/NCBI/NIH/UW entry on Oculocutaneous Albinism Type 4
[show]
Pigmentation disorders/Dyschromia (L80–L81, 709.0)
[show]
Human skin color
LCCN: sh85003229
GND: 4304941-2
NDL: 00562856
Categories:
 Albinism
 Dermatologic terminology
 Disturbances of pigmentation
 Skin pigmentation
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Cretinism
This article is about the medical condition. For other uses, see Cretin.
It has been suggested that this article be merged into Congenital hypothyroidism. (Discuss) Proposed since
March 2016.
Congenital iodine deficiency syndrome

Portrait by Eugène Trutat of a man affected with cretinism
Specialty Endocrinology
ICD-10 E00
ICD-9-CM 243
DiseasesDB 6612
eMedicine ped/501
MeSH C05.116.099.343.347
[edit on Wikidata]
Cretinism is a condition of severely stunted physical and mental growth due to

untreated congenital deficiency of thyroid hormone (congenital hypothyroidism) usually due to
maternal hypothyroidism.
Contents
[hide]
 2Treatment
 3Cause
 4History
 5Etymology
 6See also
 7References
Congenital hypothyroidism can be endemic, genetic, or sporadic. If untreated, it results in mild to severe
impairment of both physical and mental growth and development.
Poor length growth is apparent as early as the first year of life. Adult stature without treatment ranges from
100 to 160 cm (3 ft 3 in to 5 ft 3 in), depending on severity, sex, and other genetic factors. In adults,
Cretinism results in mental deterioration, swelling of the skin, loss of water and hair. [1] Bone
maturation and puberty are severely delayed. Ovulation is impeded, and infertility is common.
Neurological impairment may be mild, with reduced muscle tone and coordination, or so severe that the
person cannot stand or walk. Cognitive impairment may also range from mild to so severe that the person
is nonverbal and dependent on others for basic care. Thought and reflexes are slower.
Other signs may include thickened skin, enlarged tongue, or a protruding abdomen.
Dwarfism may also be caused by malnutrition or other hormonal deficiencies, such as insufficient growth
hormone secretion,hypopituitarism, decreased secretion of growth hormone-releasing hormone,
deficient growth hormone receptor activity and downstream causes, such as insulin-like growth factor
1 (IGF-1) deficiency.
Treatment[edit]
Sporadic and genetic cretinism results from abnormal development or function of the foetal thyroid gland.
This type of cretinism has been almost completely eliminated in developed countries by early diagnosis
by newborn screening schemes followed by lifelong treatment with thyroxine (T4).
Thyroxine must be dosed as tablets only, even to newborns, as the liquid oral suspensions and
compounded forms cannot be depended on for reliable dosing. In the case of dosing infants, the T4 tablets
are generally crushed and mixed with breast milk, formula milk or water. If the medication is mixed with
formulas containing iron or soya products, larger doses may be required, as these substances may alter
the absorption of thyroid hormone from the gut. [2] Frequent monitoring (every 2–3 weeks during the first
months of life) is recommended to ensure that infants with congenital hypothyroidism remain within the high
end of normal range, or euthyroid.
Cause[edit]
Disability-adjusted life years (DALY) lost from Iodine deficiency in 2012 per million persons.
52-163
181-217
221-221
222-310
320-505
512-610
626-626
653-976
984-1,242
1,251-3,159
Around the world, the most common cause of congenital hypothyroidism is iodine deficiency. Cretinism is
therefore most probably due to a diet deficient in iodine. It has affected many people worldwide and
continues to be a major public health problem in many countries. Iodine is an essential trace element,
necessary primarily for the synthesis of thyroid hormones. Iodine deficiency is the most common
preventable cause of brain damage worldwide.[3] Although iodine is found in many foods, it is not universally
present in all soils in adequate amounts. Most iodine, in iodide form, is in the oceans where the iodide ions
oxidize to elemental iodine, which then enters the atmosphere and falls to earth as rain, introducing iodine
to soils. Earth deficient in iodine is most common inland and in mountainous areas and areas of frequent
flooding, but can also occur in coastal regions owing to past glaciation, and leaching by snow, water and
heavy rainfall, which removes iodine from the soil. [4] Plants and animals grown in iodine deficient soils are
correspondingly deficient. Populations living in those areas without outside food sources are most at risk
of iodine deficiencydiseases.[5]
Iodine deficiency results in the impairments in varying degrees of physical and mental development. It also
causes gradual enlargement of the thyroid gland, referred to as a goitre. It is being combated in many
countries by public health campaigns of iodine administration.
History[edit]
Cretinism (Styria), copper engraving, 1815
Goiter is the most specific clinical marker of either the direct or indirect insufficient intake of iodine in the
human body. There is evidence of goiter, and its medical treatment with iodine-rich algae and burnt
sponges, in Chinese, Egyptian, and Roman ancient medical texts. In 1848, the Italian King Carlo
Alberto of Sardinia commissioned the first epidemiological study of goiter and cretinism in his Haute-
Savoie territories, where hideous cases of goiters and cretinism frequently occurred in the population. In
past centuries, the well reported social diseases prevalent among the poorer social classes and farmers,
caused by dietary and agricultural monocultures, were: pellagra, rickets, beriberi,scurvy in long-term
sailors, and the endemic goiter caused by I-deficiency. However, this disease was less mentioned in
medical books because it was erroneously considered to be an aesthetic rather than a clinical disorder.
[6]
Endemic cretinism was especially common in areas of southern Europe around the Alps and was
described by ancient Roman writers, and often depicted by medieval artists. The earliest Alpine mountain
climbers sometimes came upon whole villages of cretins.[7] Alpine cretinism was described from a medical
perspective by several travellers and physicians in the late 18th and early 19th centuries. [8] At that time the
cause was not known and it was often attributed to "stagnant air" in mountain valleys or "bad water". The
proportion of people affected varied markedly throughout southern Europe and even within very small
areas it might be common in one valley and not another. The number of severely affected persons was
always a minority, and most persons were only affected to the extent of having a goitre and some degree of
reduced cognition and growth. The majority of such cases were still socially functional in their pastoral
villages.
More mildly affected areas of Europe and North America in the 19th century were referred to as "goitre
belts". The degree of iodine deficiency was milder and manifested primarily as thyroid enlargement rather
than severe mental and physical impairment. In Switzerland, for example, where soil does not contain a
large amount of iodine, cases of cretinism were very abundant and even considered genetically caused. As
the variety of food sources dramatically increased in Europe and North America and the populations
became less completely dependent on locally grown food, the prevalence of endemic goitre diminished.
The early 20th century saw the discovery of the relationships of sporadic cretinism with congenital
hypothyroidism, and of endemic cretinism with hypothyroidism due to iodine deficiency. Both have been
largely eliminated in the developed world.
Etymology[edit]
The term cretin was once used to describe a person affected by cretinism, but, as with words such
as spastic, and lunatic, it is now considered derogatory and inappropriate.[9]Cretin became a medical term in
the 18th century, from an Occitan and an Alpine French expression, prevalent in a region where persons
with such a condition were especially common (see below); it saw wide medical use in the 19th and early
20th centuries, and was actually a "tick box" category on Victorian-era census forms in the UK. The term
spread more widely in popular English as a markedly derogatory term for a person who behaves stupidly.
Because of its pejorative connotations in popular speech, health-care workers have mostly
abandoned cretin.[citation needed]
The etymology of cretin is uncertain. Several hypotheses exist. The most common derivation provided in
English dictionaries is from the Alpine French dialect pronunciation of the word Chrétien ("(a) Christian"),
which was a greeting there. According to the Oxford English Dictionary, the translation of the French term
into "human creature" implies that the label "Christian" is a reminder of the humanity of the afflicted, in
contrast to brute beasts.[10] Other sources suggest that Christian describes the person's "Christ-like" inability
to sin, stemming, in such cases, from an incapacity to distinguish right from wrong. [11][12]
Other speculative etymologies have been offered:
 From creta, Latin for chalk, because of the pallor of those affected.

 From cretira, Grison-Romanche creature, from Latin creatus.
 From cretine, French for alluvium (soil deposited by flowing water), an
allusion to the affliction's suspected origin in inadequate soil. [13]
See also[edit]
media related to Cretinism.
 Congenital hypothyroidism
 Iodine deficiency
 Moron (psychology)
References[edit]
1. Jump up^ Councilman, W. T. (1913). "One". Disease and Its Causes.
United States: New York Henry Holt and Company London Williams
and Norgate The University Press, Cambridge, USA.
2. Jump up^ Chorazy PA, Himelhoch S, Hopwood NJ, Greger NG,
Postellon DC (July 1995). "Persistent hypothyroidism in an infant
receiving a soy formula: case report and review of the
literature".Pediatrics. 96 (1 Pt 1): 148–50. PMID 7596704.
3. Jump up^ Chen, Zu-Pei; Hetzel, BS (February 2010). "Cretinism
Revisited". Clinical Endocrinology and Metabolism. 24 (1): 39–
50. doi:10.1016/j.beem.2009.08.014. PMID 20172469.
4. Jump up^ Chapter 20. The Iodine Deficiency Disorders Thyroid
Disease Manager. Retrieved: 2011-06-26.
5. Jump up^ Gaitan E, Dunn JT (1992). "Epidemiology of iodine
deficiency". Trends Endocrinol. Metab. 3 (5): 170–
5. doi:10.1016/1043-2760(92)90167-Y. PMID 18407097.
6. Jump up^ Venturi, Sebastiano (2014). "Iodine Deficiency in the
Population of Montefeltro, A Territory in Central Italy Inside the
Regions of Emilia-Romagna, Tuscany and Marche". Internat. J. of
Anthropology. 29 (1-2): 1–12.
7. Jump up^ Fergus Fleming, Killing Dragons: The Conquest of the
Alps, 2000, Grove Press, p. 179
8. Jump up^ See, for example, William Coxe, "Account of the Vallais,
and of the Goiters and Idiots of that Country," Universal Magazine of
Knowledge & Pleasure, vol. 67, Dec. 2, 1780.
9. Jump up^ Taylor, Robert B. (2008). White Coat Tales: Medicine's
Heroes, Heritage, and Misadventures. New York: Springer.
p. 83. ISBN 0-387-73080-X.
10. Jump up^ "cretin". Oxford English Dictionary. Retrieved 11
December 2005.[dead link]
11. Jump up^ Brockett, Linus P (Feb 1858). "Cretins And Idiots". The
Atlantic Monthly. Retrieved 11 December 2005.
12. Jump up^ Robbins and Cotran – Pathologic basis of disease 8/E.
Philadelphia, PA: Sauders Elsevier. 2004.
13. Jump up^ Medvei, VC (1993). The History of Clinical Endocrinology.
Pearl River, New York: Parthenon Publishing Group.
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Type I tyrosinemia
Type I tyrosinemia
Tyrosine
Specialty endocrinology
ICD-10 E70.2
ICD-9-CM 270.2
OMIM 276700
DiseasesDB 13478
eMedicine ped/2339
MeSH D020176
[edit on Wikidata]
Type 1 tyrosinemia, also known as hepatorenal tyrosinemia or tyrosinosis, is the most severe form
of tyrosinemia, a buildup of too much of the amino acid tyrosine in the blood and tissues due to an inability
to metabolize it. It is caused by a deficiency of the enzyme fumarylacetoacetate hydrolase.
Contents
[hide]
 1Genetics
 4Treatment
 5References
Genetics[edit]
Type 1 tyrosinemia is inherited in an autosomal recessive pattern. [1] Worldwide, type I tyrosinemia affects
about 1 person in 100,000. This type of tyrosinemia is much more common in Quebec, Canada. The
overall incidence in Quebec is about 1 in 16,000 individuals. In the Saguenay-Lac-Saint-Jean region of
Quebec, type 1 tyrosinemia affects 1 person in 1,846.[2] The carrierrate has been estimated to be between 1
in 20 and 1 in 31.[3]
Fumarylacetoacetate hydrolase catalyzes the final step in the degradation of tyrosine - fumarylacetoacetate
to fumarate, acetoacetate and succinate. Fumarylacetoacetate accumulates in hepatocytes and proximal
renal tubal cells and causes oxidative damage and DNA damage leading to cell death and dysfunctional
gene expression which alters metabolic processes like protein synthesis and gluconeogenesis. The
increase in fumarylacetoacetate inhibits previous steps in tyrosine degradation leading to an accumulation
of tyrosine in the body. Tyrosine is not directly toxic to the liver or kidneys but causes dermatologic and
neurodevelopmental problems.
Pathophysiology of metabolic disorders of tyrosine, resulting in elevated levels of tyrosine in blood.

Type 1 tyrosinemia typically presents in infancy as failure to thrive and hepatomegaly. The primary effects
are progressive liver and kidney dysfunction. The liver disease causes cirrhosis, conjugated
hyperbilirubinemia, elevated AFP, hypoglycemia and coagulation abnormalities. This can lead
to jaundice, ascites and hemorrhage. There is also an increased risk of hepatocellular carcinoma. The
kidney dysfunction presents as Fanconi syndrome: Renal tubular acidosis, hypophosphatemia and
aminoaciduria. Cardiomyopathy, neurologic and dermatologic manifestations are also possible. The urine
has an odor of cabbage or rancid butter. [4]
Treatment[edit]
The primary treatment for type 1 tyrosinemia is nitisinone (Orfadin) and restriction of tyrosine in the diet.
[1]
Nitisinone inhibits the conversion of 4-OH phenylpyruvate to homogentisic acid by 4-
Hydroxyphenylpyruvate dioxygenase, the second step in tyrosine degradation. By inhibiting this enzyme,
the accumulation of the fumarylacetoacetate is prevented.[5] Previously, liver transplantation was the
primary treatment option and is still used in patients in whom nitisinone fails.
References[edit]
1. ^ Jump up to: National Organization for Rare Disorders. Physician’s
a b
Guide to Tyrosinemia Type 1

2. Jump up^ Grompe M, St-Louis M, Demers SI, al-Dhalimy M, Leclerc
B, Tanguay RM (1994). "A single mutation of the fumarylacetoacetate
hydrolase gene in French Canadians with hereditary tyrosinemia type
I". N. Engl. J. Med. 331 (6): 353–
7. doi:10.1056/NEJM199408113310603. PMID 8028615.
3. Jump up^ Laberge, C.; L. Dallaire (October 28, 1967). "Genetic
aspects of tyrosinemia in the Chicoutimi region". Can Med Assoc
J. 97 (18): 1099–1101. PMC 1923580 . PMID 6057677.
4. Jump up^ Enns GM, Packman S (2001). "Diagnosing Inborn Errors
of Metabolism in the Newborn: Clinical
Features" (PDF). NeoReviews. 2 (8): e183–e191. doi:10.1542/neo.2-
8-e183.ISSN 1526-9906.
5. Jump up^ Lock EA et al. From toxicological problem to therapeutic
use: the discovery of the mode of action of 2-(2-nitro-4-
trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), its toxicology
and development as a drug. J Inherit Metab Dis. 1998 Aug;21(5):498-
506. PMID 9728330
[hide]
type 2
Pipecolic acidemia
Saccharopinuria
Isovaleric acidemia
D-Glyceric acidemia
Carnosinemia
Histidine Histidinemia
Urocanic aciduria
G→glutamate→
α-ketoglutarate Hyperprolinemia
Proline
Hypervalinemia

G→propionyl-CoA→
succinyl-CoA 2-Methylbutyryl-CoA dehydrogenase deficiency

Cystathioninuria
Hypermethioninemia
Propionic acidemia
6-Pyruvoyltetrahydropterin synthase deficiency

Phenylketonuria
Type I tyrosinemia
Tyrosinemia
Type II tyrosinemia
G→fumarate Phenylalanine/tyrosine Type III tyrosinemia/Hawkinsinuria
Albinism: Ocular albinism (1)
Tyrosine→Melanin Oculocutaneous albinism (Hermansky–Pudlak syndrome)

Argininemia
Argininosuccinic aciduria
Urea cycle/Hyperammonemia
Carbamoyl phosphate synthetase I deficiency
G→oxaloacetate (arginine
Citrullinemia
 aspartate)
Hartnup disease
Iminoglycinuria
Cystinosis
Fumarase deficiency
Trimethylaminuria
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Genetic counseling
Genetic counseling is the process by which the patients or relatives at risk of an inherited disorder are
advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and
the options open to them in management and family planning. This complex process can be separated into
diagnostic (the actual estimation of risk) and supportive aspects. [1]
Contents
[hide]
 1Genetic counselors
 2Patients
 3Counseling session structure
 4Reasons for testing
o 4.1Detectable conditions
o 4.2Hereditary Cancer
 5Genetic counselors as support
o 5.1Prenatal genetic counseling
o 5.2Referral
 6Attitudes toward counseling
 7See also
 8Footnotes
Genetic counselors[edit]
The National Society of Genetic Counselors (NSGC) officially defines genetic counseling as the
understanding and adaptation to the medical, psychological and familial implications of genetic
contributions to disease.[2] This process integrates:
 Interpretation of family and medical histories to assess the chance of
disease occurrence or recurrence.
 Education about inheritance, testing, management, prevention,
resources
 Counseling to promote informed choices and adaptation to the risk or
condition.
A genetic counselor is an expert with a Master of Science degree in genetic counseling. In the United
States they are certified by the American Board of Genetic Counseling.[1]In Canada, genetic counselors
are certified by the Canadian Association of Genetic Counsellors. Most enter the field from a variety of
disciplines, including biology, genetics,nursing, psychology, public health and social work.[citation needed] Genetic
counselors should be expert educators, skilled in translating the complex language of genomic medicine
into terms that are easy to understand.
Genetic counselors work as members of a health care team and act as a patient advocate as well as a
genetic resource to physicians. Genetic counselors provide information and support to families who have
members with birth defects or genetic disorders, and to families who may be at risk for a variety of inherited
conditions. They identify families at risk, investigate the problems present in the family, interpret information
about the disorder, analyze inheritance patterns and risks of recurrence, and review available genetic
testingoptions with the family.
Genetic counselors are present at high risk or specialty prenatal clinics that offer prenatal diagnosis,
pediatric care centers, and adult genetic centers. Genetic counseling can occur before conception (i.e.
when one or two of the parents are carriers of a certain trait) through to adulthood (for adult onset genetic
conditions, such as Huntington's diseaseor hereditary cancer syndromes).
Patients[edit]
Any person may seek out genetic counseling for a condition they may have inherited from their biological
parents.
A woman, if pregnant, may be referred for genetic counseling if a risk is discovered through prenatal
testing (screening or diagnosis). Some clients are notified of having a higher individual risk
for chromosomal abnormalities or birth defects. Testing enables women and couples to make a decision as
to whether or not to continue with their pregnancy, and helps provide information that can be used to
prepare for the birth of a child with medical issues.
A person may also undergo genetic counseling after the birth of a child with a genetic condition. In these
instances, the genetic counselor explains the condition to the patient along with recurrence risks in future
children. In all cases of a positive family history for a condition, the genetic counselor can evaluate risks,
recurrence and explain the condition itself.
Counseling session structure[edit]

The goals of genetic counseling are to increase understanding of genetic diseases, discuss disease
management options, and explain the risks and benefits of testing. [3]Counseling sessions focus on giving
vital, unbiased information and non-directive assistance in the patient's decision-making process. Seymour
Kessler, in 1979, first categorized sessions in five phases: an intake phase, an initial contact phase, the
encounter phase, the summary phase, and a follow-up phase. [4] The intake and follow-up phases occur
outside of the actual counseling session. The initial contact phase is when the counselor and families meet
and build rapport. The encounter phase includes dialogue between the counselor and the client about the
nature of screening and diagnostic tests. The summary phase provides all the options and decisions
available for the next step. If counselees wish to go ahead with testing, an appointment is organized and
the genetic counselor acts as the person to communicate the results.
Reasons for testing[edit]

Families or individuals may choose to attend counseling or undergo prenatal testing for a number of
reasons.[5]
 Family history of a genetic condition or chromosome abnormality

 Molecular test for single gene disorder
 Increased maternal age (35 years and older)
 Increased paternal age (40 years and older)
 Abnormal maternal serum screening results or ultrasound findings
 Increased nuchal translucency measurements on ultrasound
 Strong family history of cancer
 Predictive testing for adult-onset conditions
Detectable conditions[edit]
Many disorders cannot occur unless both the mother and father pass on their genes, such as Cystic
Fibrosis. Some diseases can be inherited from one parent, such asHuntington disease, and DiGeorge
syndrome. Other genetic disorders are the cause of an error or mutation occurring during the cell division
process (e.g.trisomy). Testing can reveal conditions that are easily treatable as long as they are detected
(Phenylketonuria or PKU). Genetic tests are available for a number of genetic conditions including but not
limited to:
 Down syndrome
 Sickle-cell anemia
 Tay-Sachs disease
 Muscular dystrophy
Hereditary Cancer[edit]
Patients may be referred to a genetic counselor based on their cancer diagnosis, or a strong family history
of cancer. It is estimated that only 5-10% of cancers are hereditary, meaning that these cancers are due to
a gene mutation that has been passed down in the family.[6] Some examples of known cancer syndromes
are hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer and Li-
Fraumeni syndrome.[7] Meeting with a genetic counselor before undergoing genetic testing will help an
individual to understand the test and what the results may mean for themselves and their family. Once the
results are received, genetic counselors can help the patient to understand a positive or negative result.
This counseling may involve providing emotional support, discussing recommendations for preventative
care, screening recommendations or referrals to support groups or other resources. [8] For patients who
have already been diagnosed with cancer, a positive test result may influence how the cancer is treated. [8]
Genetic counselors as support[edit]

Genetic Alliance states that counselors provide supportive counseling to families, serve as patient
advocates and refer individuals and families to community or state support services. They serve as
educators and resource people for other health care professionals and for the general public. Many engage
in research activities related to the field of medical genetics and genetic counseling. The field of genetic
counseling is rapidly expanding and many counselors are taking on "non-traditional roles" which includes
working for genetic companies and laboratories. [citation needed] When communicating increased risk, counselors
anticipate the likely distress and prepare patients for the results. Counselors help clients cope with and
adapt to the emotional, psychological, medical, social, and economic consequences of the test results.
Each individual considers their family needs, social setting, cultural background, and religious beliefs when
interpreting their risk.[9] Clients must evaluate their reasoning to continue with testing at all. Counselors are
present to put all the possibilities in perspective and encourage clients to take time to think about their
decision. When a risk is found, counselors frequently reassure parents that they were not responsible for
the result. An informed choice without pressure or coercion is made when all relevant information has been
given and understood.
Prenatal genetic counseling[edit]

If an initial noninvasive screening test reveals a risk to the baby, clients are encouraged to attend genetic
counseling to learn about their options. Further prenatal investigation is beneficial and provides helpful
details regarding the status of the fetus, contributing to the decision-making process. Decisions made by
clients are affected by factors including timing, accuracy of information provided by tests, and risk and
benefits of the tests. Counselors present a summary of all the options available. Clients may accept the risk
and have no future testing, proceed to diagnostic testing, or take further screening tests to refine the risk.
Invasive diagnostic tests possess a small risk of miscarriage (1-2%) but provide more definitive results.
While families seek direction and suggestions from the counselors, they are reassured that no right or
wrong answer exists. When discussing possible choices, counselor discourse predominates and is
characterized by examples of what some people might do. Discussion enables people to place the
information and circumstances into the context of their own lives. [10] Clients are given a decision-making
framework they can use to situate themselves. Counselors focus on the importance of individual choice
based on the experiences, morals, and viewpoints of the couple/individual/family. Testing is offered to
provide a definitive answer regarding the presence of a certain genetic condition or chromosomal
abnormality. There is often no therapy or treatment available for these conditions, and as such parents may
choose to terminate the pregnancy.
Referral[edit]
After attending prenatal counseling, women have the option of accepting the risk revealed and having no
further investigations during their pregnancy. They may choose to undergo noninvasive screening
(e.g. ultrasound, triple screen, cell-free fetal DNA screening) or invasive diagnostic testing
(amniocentesis or chorionic villus sampling).
After counseling for other hereditary conditions, the patient may be presented with the option of having
genetic testing. In some circumstances no genetic testing is indicated, other times it may be useful to begin
the testing process with an affected family member. The genetic counselor also reviews the advantages
and disadvantages of genetic testing with the patient.
Attitudes toward counseling[edit]

The plethora of information available can be overwhelming and counselors spend a large proportion of time
clarifying details. Prenatal screening was first introduced nearly four decades ago, yet gaps still exist in
public knowledge about the screening program. The general public is familiar with Down syndrome (trisomy
21), but is not aware of more uncommon conditions such as trisomy 18 (historically known as Edwards
syndrome) and trisomy 13 (Patau syndrome). Clients are usually aware of diagnostic testing from friends,
TV/press, or because of family history.
No simple correlation has been found between the change in technology to the changes in values and
beliefs towards genetic testing.[11]
See also[edit]
 Whole genome sequencing
 National Society of Genetic Counselors
 Reprogenetics
 Genomic counseling
Footnotes[edit]
1. Jump up^ "Definitions of Genetic Testing". Definitions of Genetic
Testing (Jorge Sequeiros and Bárbara Guimarães). EuroGentest
Network of Excellence Project. 2008-09-11. Archived from the
original on February 4, 2009. Retrieved 2008-08-10.
2. Jump
up^ http://www.nsgc.org/About/FAQsDefinitions/tabid/97/Default.aspx
3. Jump up^ Genetic Alliance Site [Internet]. [cited 2010 Oct 29].
Available from:http://www.geneticalliance.org/.
4. Jump up^ Hodgson, JM; Gillam, LH; Sahhar, MA; Metcalfe, SA (Feb
2010). ""Testing times, challenging choices": an Australian study of
prenatal genetic counseling". Journal of Genetic Counseling. 19 (1):
22–37. doi:10.1007/s10897-009-9248-6.PMID 19798554.
5. Jump up^ Macdonald, F (1 November 2008). "Practice of prenatal
diagnosis in the UK". Clinical Risk. 14 (6): 218–
221. doi:10.1258/cr.2008.080062.
6. Jump up^ Schneider, Katherine (2011). Counseling About Cancer.
New Jersey: John Wiley & Sons. ISBN 1118119916.
7. Jump up^ "Family Cancer Syndromes". www.cancer.org.
8. ^ Jump up to: "Genetic Testing for Hereditary Cancer
a b
Syndromes". National Cancer Institute. Retrieved 2016-03-25.

9. Jump up^ Dolan, SM (Aug 2009). "Prenatal genetic
testing". Pediatric annals. 38 (8): 426–30.doi:10.3928/00904481-
20090723-05. PMID 19711880.
10. Jump up^ Stefansdottir, V; Skirton, H; Jonasson, K; Hardardottir, H;
Jonsson, JJ (Jul 2010). "Effects of knowledge, education, and
experience on acceptance of first trimester screening for
chromosomal anomalies". Acta Obstetricia et Gynecologica
Scandinavica.89 (7): 931–
8. doi:10.3109/00016341003686073. PMID 20235896.
11. Jump up^ Singer, E; Couper, MP; Raghunathan, TE; Van Hoewyk, J;
Antonucci, TC (Fall 2008)."Trends in U.S. Attitudes Toward Genetic
Testing, 1990-2004". Public Opinion Quarterly. 72 (3): 446–
458. doi:10.1093/poq/nfn033. PMC 3045776 .PMID 22476359.
 Alexandra Minna Stern, Telling Genes: The Story of Genetic
Counseling in America. Baltimore, MD: Johns Hopkins University
Press, 2012.
 National Society of Genetic Counselors
 American Board of Genetic Counseling
 Canadian Association of Genetic Counsellors
 Association of Genetic Nurses and Counsellors (UK)
 EuroGentest
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World Wide Fund for Nature

From Wikipedia, the free encyclopedia

World Wide Fund for Nature

Motto Building a future in which people and nature thrive.

Formation 29 April 1961; 55 years ago a

Godfrey A. Rockefeller [2][citation needed]

Type Charitable trust

Headquarters Avenue du Mont-Blanc,

Coordinates 46.4171864°N 6.2709482°E

Key people  Prince Philip, Duke of

 Marco Lambertini, Director General

Revenue(2010[3]) € 654 million (2013)

Slogan "For a Living Planet"

The World Wide Fund for Nature (WWF) is an international non-governmental organization founded in

 1The Conservation Foundation

The Conservation Foundation[edit]

The WWF hot air balloon in Brazil

In the 1990s, WWF revised its mission statement to:

 conserving the world's biological diversity;

In 1996, the organization obtained general consultative status from UNESCO.

The giant panda has become the symbol of WWF.

Mekong River dolphins report[edit]

Alleged human-rights abuses[edit]

1961–1976 Prince Bernhard of Lippe-Biesterfeld

1976–1981 John Hugo Loudon

1981–1996 Prince Philip, Duke of Edinburgh

1996–1999 Syed Babar Ali

2000 Ruud Lubbers

2000–2001 Sara Morrison

2001–2010 Chief Emeka Anyaoku

The 1001: A Nature Trust[edit]

Notable programs and campaigns[edit]

January 29, 2010.

Fund for Nature. 2014. p. 44. Retrieved 2015-09-17.

11. Jump up^ The Conservation Foundation: History and Founders

18. Jump up^ "WWF - WWF in the 60's". WWF. Retrieved 10

human rights abuses of tribal people in Cameroon". The Guardian.

World Wide Fund for Nature

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