Angelman Syndrome

Estefania Caro

Introduction to Special Education 203

Angelman Syndrome Research Paper

Tues. April 14, 2020

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Angelman Syndrome

Angelman Syndrome (AS) is a neurological disease that primarily affects the nervous

system and can cause many neurological and psychological problems including seizures, difficult

behaviors, sleeping problems, and movement disorders. Dr. Harry Angelman first reported the

syndrome in 1965. It was forgotten about until the 1980s when the first reports of AS appeared

in North America in 1987. It was a rare disorder found in 1 in 15,000 births. This led to the

discovery of the four causes of AS and the treatments to help individuals born with this disease.

In 1965, Dr. Harry Angelman, an English pediatrician, diagnosed three handicapped

children with a condition originally known as the “happy puppet” syndrome. Dr. Angelman

noted that all three children had similar dysmorphic facial features and characteristics of severe

learning disabilities, jerky movements, inability to speak, easily provoked laughter, and seizures

(Clayton-Smith and Laan). He hesitated to write about the children’s illness in medical journals.

However, during his investigation, Dr. Angelman went on a holiday trip to Italy where he visited

the Castelvecchio Museum in Verona. He saw an oil painting called “A Boy with a Puppet”

where he noticed the boy’s laughing face and the puppet reminded him of the jerky

movements of his patients. It gave Dr. Angelman the idea of writing an article about the

children with the title of Puppet Children. The name “happy puppet” syndrome did not please

parents, which was later changed to Angelman Syndrome (“About Angelman Syndrome”). His

article was published in 1965, but his research was forgotten for over twenty years until the

first cases of AS appeared in North America in the 1980s.

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In 1987, Ellen Magenis, a physician at the Oregon Health Science Center, identified

children with micro deletions of chromosome 15. They were expected to have the Prader-Willi

Syndrome, however, these children had seizures and severe developmental delay, which were

features not expected to be found in that specific syndrome (“About Angelman Syndrome”).

This finding led to the discovery of what causes children to be born with AS. AS is caused by a

genetic mutation on chromosome 15. The name of this gene is UBE3A. The UBE3A contains

instructions to a protein that plays an important role in the normal development and function

of the nervous system. Normally, people inherit one copy of the UBE3A gene from each parent,

and both copies become active in most of the body’s tissues. AS occurs when only one copy of

the gene is active in certain parts of the brain, which causes the baby to develop several

neurological and psychological disorders (“Angelman syndrome”). There are four types of AS

involving problems with chromosomes or mutations in the UBE3A gene.

In 70% of cases, Angelman Syndrome is caused by a deletion of chromosome 15q11-13.

Most cases of AS occur when a segment of the maternal chromosome 15, inherited from the

person’s mother, containing this gene is deleted. Several different genetic mechanisms can

inactivate or delete the maternal copy of the UBE3A gene (“Angelman syndrome”). According

to the article, “Angelman syndrome: a review of the clinical and genetic aspects” by J Clayton-

Smith and L Laan, it mentions that about 20% of cases, the maternal copy of the UBE3A gene is

altered (mutated). 2-3% of cases have uniparental disomy (UPD), which is when a person

inherits two copies of chromosome 15 from his or her father (paternal copies) instead of one

copy from each parent. Imprinting defects account for 3-5% of patients without deletions or

UPD, but with abnormal chromosome 15 methylation, signifying a defect in imprinting. Most
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cases of AS are not inherited. It is rare when a genetic change responsible for AS can be

inherited, but it is possible for a mutation in the UBE3A gene to be passed from one generation

to the other. AS is a rare disease, which is why 1 in approximately 15,000 to 20,000 individuals

are born with this syndrome.

Angelman Syndrome causes many neurological and psychological problems.

Characteristics of this neuro-genetic disorder include: seizures, developmental delay, speech

impairments, movement disorders, sleep problems, dysmorphic facial features, and a happy,

excitable demeanor with frequent smiling and laughter. According to the National Institute of

Neurological Disorders and Stroke, “Infants with AS appear normal at birth but often have

feeding problems in the first months of life and exhibit noticeable developmental delays by 6-

12 months. Seizures often begin between 2-3 years of age and occur in 80-85 percent of those

with AS.” Usually many families will not know their child has AS until a little over a year. All AS

patients have delayed motor milestones. They sit unsupported at around twelve months, crawl

or bottom shuffle at 18-24 months, and walk anywhere from eighteen months to seven years

(Clayton-Smith and Laan). They are usually unbalanced and walk with a stiff leg, they hold their

arms up with the wrists and elbows bent, and may flap their hands repeatedly when walking or

when they are excited. Other AS symptoms include: intellectual disability, hyperactivity, short

attention span, and have trouble going to sleep and usually sleep less than others. Some

Angelman dysmorphic facial features include a small chin, deep-set eyes, a wide mouth, widely-

spaced teeth, puffiness around the eye or folded eye lids, and an abnormally flat back of the

head. They usually always appear very happy and may often have inappropriate episodes of

unprovoked, prolonged laughter and smiling.

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There is currently no cure or medication to treat Angelman Syndrome since

chromosomes cannot be repaired. According to the National Organization for Rare Disorders,

AS treatment focuses on the child's medical problems and developmental delays. Many parents

are recommended to take their children to physical therapy to help with joint mobility and

movement, speech therapy, occupational therapy, and behavioral therapy to help discourage

unwanted behaviors. Having strict bedtime routines and sedating medications can be helpful

for sleeping disorders. Anticonvulsant is an anti-seizure medication that can be given to those

who experience seizures. “Usually seizures can be adequately controlled with a single

medication but in some cases seizure control may be difficult and multiple medications are

needed. No one anticonvulsant drug has been proven to be most effective in all cases”

(“Angelman Syndrome”). Families usually have to take turns taking care of children with AS,

especially if they frequently get seizures. As individuals move from adolescence to adulthood,

seizures improve or resolve for most people.

Furthermore, most children with Angelman Syndrome benefit from speech therapy.

Most individuals learn to communicate non-verbally or by using communication devices as they

get older, such as computer picture-based systems, voice emitting devices and other modern

uses of technology. Many teens and adults have frequent twitching in their hands, called

myoclonus, which can spread to their arms and the rest of the body. Myoclonus is not seizure

activity but can interfere with quality of life and can be treated with medication (“Angelman

Syndrome Information Page”). Early intervention is important to ensure that individuals with AS

reach their potential. Special social support and other medical services are available for parents

and caregivers.
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“Life with Angelman Syndrome: Managing Every Life” is a short clip on YouTube posted

by Ovid Therapeutics. This video shows and explains how parents live with a child who was

diagnosed with Angelman Syndrome at 15 months. Parents get emotional when they find out

their child has AS because then they get told that their child would be unable to perform

certain functions such as walking or talking. It’s mostly challenging for the parents because they

don’t get much sleep either and they’re constantly worrying about what’s going to trigger their

child’s next seizure, and if they’re up all night, it also makes everyone have a rough day the next

day. Their son from the video is still learning how to walk, and understands what people are

saying but he cannot talk. He is able to communicate with them in other ways. Even though the

parents face difficult times with children with AS, they still get excited and happy when they

finally see their child hit some milestones that they were told by doctors would never happen.

I believe it’s very important to be patient with a child who has Angelman Syndrome.

They will take a longer time to accomplish certain tasks, but with the right therapy and within

time they will get to one day do those tasks. All the neurological and psychological problems

that these children face including: seizures, difficult behaviors, sleeping problems, and

movement disorders, will get better within time. As they grow into their teenage and adulthood

years, most of the symptoms get better or are reduced. It is very important for them to be

diagnosed at an early age to get early interventions and proper care and treatments so they do

not struggle as much when they are older.

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Works Cited

“About Angelman Syndrome.” The Carolina Institute for Developmental Disabilities at UNC, The

Carolina Institute for Developmental Disabilities, www.cidd.unc.edu/Angelman-

Syndrome/about.aspx. Accessed 13 April 2020.

“Angelman Syndrome.” NORD, National Organization for Rare Disorders, rarediseases.org/rare-

diseases/angelman-syndrome/. Accessed 14 April 2020.

“Angelman syndrome.” U.S. National Library of Medicine, National Library of Medicine, 31 Mar.

2020, ghr.nlm.nih.gov/condition/angelman-syndrome#statistics. Accessed 13 April 2020.

“Angelman Syndrome Information Page.” National Institute of Neurological Disorders and Stroke,

U.S. Department of Health and Human Services, 27 Mar. 2019,

www.ninds.nih.gov/Disorders/All-Disorders/Angelman-Syndrome-Information-Page. Accessed

14 April 2020.

Clayton-Smith, J, and L Laan. “Angelman Syndrome: a Review of the Clinical and Genetic

Aspects.” Journal of Medical Genetics, BMJ Publishing Group Ltd, 1 Feb. 2003,

jmg.bmj.com/content/40/2/87.full. Accessed 13 April 2020.

Ovid Therapeutics. “Life with Angelman Syndrome: Managing Everyday Life | Ovid.” YouTube,

uploaded by Ovid Therapeutics, 10 July 2018, https://www.youtube.com/watch?

v=fqCkEm57YqM. Accessed 14 April 2020.