Genetic Disorders

I. Duane Syndrome (DS)

What is Duane Syndrome?

Duane syndrome is a rare congenital eye movement disorder. Other names for this condition include:
Duane's Retraction Syndrome (or DR syndrome), Eye Retraction Syndrome, Retraction Syndrome,
Congenital retraction syndrome and Stilling-Turk-Duane Syndrome. DS is a misdirection of the nerve
fiber causing the eyes to not contract when it is supposed and vice versa.

Signs and Symptoms

Clinically, Duane syndrome is often subdivided into three types, each with associated symptoms.

 Type 1: The affected eye, or eyes, has limited ability to move outward toward the ear, but the
ability to move inward toward the nose is normal or nearly so. The eye opening narrows and the
eyeball pulls in when looking inward toward the nose, however the reverse occurs when looking
outward toward the ear. About 78 percent of all DS cases are Type 1.

 Type 2: The affected eye, or eyes, has limited ability to move inward toward the nose, but the
ability to move outward
toward the ear is normal or
nearly so. The eye opening
narrows and the eyeball
pulls in when looking inward
toward the nose. About 7
percent of all DS cases are
Type 2.

 Type 3: The affected eye, or

eyes, has limited ability to
move both inward toward
the nose and outward
toward the ears. The eye
opening narrows and the
eyeball pulls in when looking
inward toward the nose.
About 15 percent of all DS
cases are Type 3.
What is the cause of Duane Syndrome?

Duane Syndrome is cause by the miswiring of the medial

(inward) and the lateral (outward) rectus which are
muscles of the eyes. Patients with DS also lack the
presence of the abducens nerve which is responsible for
eye movement.

According to researchers DS results from either a genetic

or environmental disturbance during embryonic
development, since ocular muscles and cranial nerves
develop between the 3rd or 8th week of pregnancy.

II. Parkinson’s Disease (PD)

What is Parkinson’s Disease?

Parkinson’s Disease is a neurological disease that affects movement. It affects several regions of the
brain, especially a region known as "substantia nigra" that helps controlling balance and movement.
Most cases of PD are sporadic (with no family history). However, in some families, there are several
cases of Parkinson disease. Familial cases of Parkinson disease, and maybe some sporadic cases,
can be caused by changes (mutations) in several genes, such as:

 Mutations in the SNCA (PARK1), LRRK2 (PARK8), and VPS35 (PARK17) genes are inherited in an
autosomal dominant manner.
 Mutations in genes PARK2, PARK7, and PINK1 (PARK6) appear to be inherited in a recessive manner.
 Very rare mutations in the TAF1 gene cause Parkinson disease with X-linked inheritance.
 Mutations in some genes, including GBA and UCHL1 (PARK 5), do not seem to cause Parkinson
disease, but to increase the risk of developing the disease in some families.

Signs and Symptoms

The symptoms start slowly, but progress over time, impairing everyday activities such as
walking, talking, or completing simple tasks. The four main symptoms are:

 tremors of the hands, arms, legs, jaw, or head, specially at rest

 rigidity, or stiffness
 bradykinesia or slow movement
 postural instability or inability to find balance
 Other symptoms may include emotional problems, trouble swallowing and speaking; urinary
problems or constipation; skin problems; sleep problems, low blood pressure when standing
up from sitting or lying down (postural hypotension), and inexpressive face. Some people will
loose their mental abilities (dementia).

What is the cause of Parkinson’s Disease?

Parkinson disease occurs when the nerve cells in the brain that make dopamine, a chemical
messenger which transmits signals within
the brain to produce smooth physical
movements, are slowly destroyed. Without
dopamine, the nerve cells in the part of the
brain known as the substantia nigra cannot
properly send messages. This leads to
progressive loss of muscle function.
Exactly why these brain cells waste away
is unknown.
Recent studies have shown that
people with Parkinson’s disease also
experience damage to the nerve endings
that produce the neurotransmitter
norepinephrine. Norepinephrine, which is
closely related to dopamine, is the main
chemical messenger of the sympathetic
nervous system, the part of the nervous system that controls the automatic functions of the body,
including pulse and blood pressure. The loss of norepinephrine may explain some of the non-motor
features seen in Parkinson disease, including fatigue and problems with blood pressure regulation.

III. Marfan Syndrome

What is Marfan Syndrome?

Marfan syndrome is an autosominal dominant multisystem disorder that affects the connective tissue
in one’s body. It is characterized by manifestations in the skeletal, cardiovascular, and ocular
systems.

What are the symptoms of Marfan syndrome?

The most common symptom of Marfan syndrome is myopia (nearsightedness from the increased
curve of the retina due to connective tissue changes in the globe of the eye). About 60 percent of
individuals who have Marfan syndrome have
lens displacement from the center of the pupil
(ectopia lentis). Individuals who have Marfan
syndrome also have an increased risk for retinal
detachment, glaucoma and early cataract
formation.
Other common symptoms:
 bone overgrowth and loose joints (joint
laxity).
 long thin arms and legs
(dolichostenomelia).
 Overgrowth of the ribs which can cause
the sternum to bend inward (pectus excavatum
 or funnel chest) or push outward (pectus carinatum or pigeon breast)
 Curvature of the spine (scoliosis) is another common skeletal symptom that can be mild or
severe and progressively worsen with age. Scoliosis shortens the trunk also contributes to the
arms and legs appearing too long.
Cardiovascular malformations are the most life threatening symptom of Marfan syndrome. They
include* dilated aorta just as it leaves the heart (at the level of the sinuses of Valsalva), mitral valve
prolapse, tricuspid valve prolapse, enlargement of the proximal pulmonary artery, and a high risk for
aortic tear and rupture(aortic dissection).

What is the cause of Marfan Syndrome?

Marfan syndrome is caused by a defect in the gene that enables your body to produce a protein that
helps give connective tissue its elasticity and strength.

Most people with Marfan syndrome inherit the abnormal gene from a parent who has the disorder.
Each child of an affected parent has a 50-50 chance of inheriting the defective gene. In about 25
percent of the people who have Marfan syndrome, the abnormal gene doesn't come from either
parent. In these cases, a new mutation develops spontaneously.

IV. Noonan Syndrome

What is Noonan Syndrome?

Noonan syndrome was first recognized as a unique entity in 1963 when Noonan and Ehmke
described a series of patients with unusual facies and multiple malformations, including congenital
heart disease. These patients were previously thought to have a form of Turner syndrome, with which
Noonan syndrome shares numerous clinical features. The observation that patients with Noonan
syndrome have normal karyotypes was important in allowing the distinction to be made between the
Turner and Noonan syndromes.

What are the symptoms of Noonan Syndrome?

 A characteristic facial appearance.

 Short stature.
 Heart defect present at birth (congenital heart defect).
  A broad or webbed neck.
 Minor eye problems such as strabismus in up to 95 percent of individuals.
 Bleeding problems such as a history of abnormal bleeding or bruising.
 An unusual chest shape with widely-spaced and low set nipples.
 Developmental delay of varying degrees, but usually mild.
 In males, undescended testes (cryptorchidism).

What is the cause of Noonan Syndrome?

Noonan syndrome is caused by changes in one of several autosomal

dominant genes. A person who has Noonan syndrome may have inherited
an altered (mutated) gene from one of his or her parents, or the gene
change may be a new change due to an error carried by the egg or sperm or
occurring at conception. Alterations in four genes - PTPN11, SOS1,
RAF1 and KRAS - have been identified to date.

V. Osteogenesis Imperfecta (Brittle Bone Disease)

What is Noonan Syndrome?

Osteogenesis imperfecta (OI) is a genetic disorder that causes a person's bones to break easily, often
from little or no apparent trauma. OI is also called "brittle bone disease." OI varies in severity from
person to person, ranging from a mild type to a severe type that causes death before or shortly after
birth. In addition to having fractures, people with OI also have teeth problems (dentinogenesis
imperfecta), and hearing loss when they are adults. People who have OI may also have muscle
weakness, loose joints (joint laxity) and skeletal malformations.

What are the symptoms of Osteogenesis imperfecta?

Osteogenesis imperfecta (OI) causes bones to be fragile and easily broken and is also responsible for
other health problems.
  Type I OI is the mildest form of the condition. People who have type I OI have bone fractures
during childhood and adolescence often due to minor trauma When these individuals reach
adulthood they have fewer fractures.
 Type II OI is the most severe form of OI. Infants with type II have bones that appear bent or
crumpled and fractured before birth. Their chest is narrow and they have fractured and
misshapen ribs and underdeveloped lungs. These infants have short, bowed arms and legs;
hips that turn outward; and unusually
soft skull bones. Most infants with
type II OI are stillborn or die shortly
after birth, usually from breathing
failure.
 Type III OI also has relatively severe
signs and symptoms. Infants with OI
type III have very soft and fragile
bones that may begin to fracture
before birth or in early infancy. Some
infants have rib fractures that can
cause life-threatening problems with
breathing. Bone abnormalities tend to
get worse over time and often
interfere with the ability to walk.
 Type IV OI is the most variable form
OI. Symptoms of OI type IV can range from mild to severe. About 25 percent of infants with
OI type IV are born with bone fractures. Others may not have broken bones until later in
childhood or adulthood. Infants with OI type IV have leg bones that are bowed at birth, but
bowing usually lessens as they get older.
Some types of OI are also associated with progressive hearing loss, a blue or grey tint to the part of
the eye that is usually white (the sclera), teeth problems (dentinogenesis imperfecta), abnormal
curvature of the spine (scoliosis) and loose joints. People with this condition may have other bone
abnormalities and are often shorter in stature than average.

What is the cause of Osteogenesis Imperfecta?

The vast majority (90 percent) of OI is caused by a single dominant mutation in one of two type I
collagen genes: COL1A1 or COL1A2.The COL1A1 and COL1A2 genes provide instructions for
making proteins that are used to create a larger molecule called type I collagen. This type of collagen
is the most common protein in bone, skin and other tissues that provide structure and strength to the
body (connective tissues). OI type VII is caused by recessive mutations in the CRTAP gene.
References:

Learning About Duane Syndrome. (2017, June 29). Retrieved February 02, 2018, from
https://www.genome.gov/11508984/learning-about-duane-syndrome/

Learning About Marfan Syndrome. (2017, May 30). Retrieved February 02, 2018, from
https://www.genome.gov/19519224/learning-about-marfan-syndrome/

Learning About Noonan Syndrome. (2013, December 23). Retrieved February 02, 2018, from
https://www.genome.gov/25521674/learning-about-noonan-syndrome/

Learning About Osteogenesis Imperfecta. (2017, July 5). Retrieved February 02, 2018, from
https://www.genome.gov/25521839/learning-about-osteogenesis-imperfecta/

McGovern, M. M., MD,PhD. (2017, July 19). Noonan Syndrome (L. O. Rohena MD, Ed.). Retrieved
February 02, 2018, from https://emedicine.medscape.com/article/947504-overview

Marfan syndrome. (2017, August 15). Retrieved February 02, 2018, from
https://www.mayoclinic.org/diseases-conditions/marfan-syndrome/symptoms-causes/syc-
20350782

Parkinson disease. (n.d.). Retrieved February 02, 2018, from

https://rarediseases.info.nih.gov/diseases/10251/parkinson-disease