What are the other Names for this Condition? (Also known as/Synonyms)

• Female Pseudo-Turner Syndrome
• Turner Syndrome in Female with X Chromosomes
• Ullrich-Noonan Syndrome

What is Noonan Syndrome? (Definition/Background Information)

• Noonan Syndrome is an inherited disorder that causes an abnormal development of various parts of the body. It is considered as a type of dwarfism
• Individuals with Noonan Syndrome have unusual facial characteristics, short stature, heart defects, other physical abnormalities and possibly lower intelligence
• Currently, there is no cure for Noonan Syndrome. The treatment is aimed at managing the signs and symptoms of the disorder
• Noonan Syndrome is a lifelong disorder; the severity of the heart defects determine the life expectancy of an individual

Who gets Noonan Syndrome? (Age and Sex Distribution)

• Noonan Syndrome is an inherited disorder present since birth. The incidence of the condition is 1 in 1000
• The incidence of Noonan Syndrome is the same between the male and female population
• There is no geographical, racial, and ethnicity preference for this disorder; the condition is observed globally

What are the Risk Factors for Noonan Syndrome? (Predisposing Factors)

• The only risk factor associated with Noonan Syndrome is family history of the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Noonan Syndrome? (Etiology)

• Noonan Syndrome is caused by mutation in one of the following genes:
  • PTPN11 gene
  • SOS1 gene
  • RAF1 gene
  • KRAS gene
  • NRAS gene
  • BRAF gene
• The mutation can be inherited from a parent who carries the defective gene; the gene is inherited in an autosomal dominant pattern
• It can also develop because of a new mutation in children who do not have a genetic predisposition for the condition
• Defects in the gene cause them to produce proteins that are overactive and disrupt the normal process of growth and development

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children who do not inherit the abnormal gene will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Noonan Syndrome?

Some individuals have mild and some severe symptoms of Noonan Syndrome. The signs and symptoms associated with the condition include:

• Feeding difficulties in infants
• Downward slanting eyes or widely set eyes, sagging eyelids
• Low-set or abnormally-shaped ears, backward rotated ears, thick helix of the ear, incomplete folding of the ears
• Small, upturned nose
• Small jaw, crowding of the lower teeth
• Deeply grooved philtrum (top lip line), high arched palate
• Excess skin in the back of the neck, low hairline at the nape of the neck
• High hairline at the front of the head, curly hair
• Large head, triangular-shaped face, broad forehead
• Mild mental retardation
• Short stature (50% of the individuals have this feature)
• Small penis, undescended testicles (the testes are not present in their usual location inside the scrotum)
• Unusual chest shape - described as pectus excavatum and pectus carinatum
• Webbed and short-appearing neck
• Abnormal curvature of the spine (kyphosis or scoliosis)
• Delayed puberty
• A variety of heart defects, such as atrial septal defect, heart murmur
• Hypotonia - low muscle tone

How is Noonan Syndrome Diagnosed?

The diagnosis of Noonan Syndrome may involve:

• Evaluation of medical history along with a thorough physical exam
• Various tests to be done will include:
  • Platelet count
  • Blood clotting factor test
  • EKG/ ECG/ Electrocardiogram: A test to record the electrical activity of the heart
  • Chest X-ray
  • Hearing tests
  • Genetic testing
  • Echocardiogram

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Noonan Syndrome?

The complications associated with Noonan Syndrome are:

• Pulmonary valvular stenosis: Stenosis of valve separating the right ventricle and pulmonary artery
• Heart-related abnormalities, which includes:
  • Heart failure
  • Cardiomyopathy: A condition of abnormal heart muscles
• Excessive bleeding during childbirth
• Infertility in males – it is important to note that females have normal fertility
• Gastrointestinal system defects:
  • Failure to thrive as an infant
  • Decreased appetite
  • Frequent or forceful vomiting
  • Swallowing difficulties
• Genito-urinary system:
  • Cryptorchidism - undescended testicles
• Lymphatic system:
  • Posterior cervical hygroma: Congenital malformation of the lymphatic system
  • Lymphedema - building up of body fluid in the tissues
• Developmental complications:
  • Clumsiness, poor coordination
  • Motor delay
  • Learning disabilities
  • Speech and language delays
• Hematologic:
  • Easy bruising
  • Low patent count
  • Blood clotting disorders
• Neurological:
  • Arnold-Chiari malformation (malformation of the brain)
• Joint contractures or tightness, joint hyper-extensibility or looseness
• Growth retardation
• Winging of the scapula
• Extra fold of skin at the inner corner of the eye
• Vision defects such as:
  • Strabismus
  • Bulging eyes
  • Inward or outward turning of the eye
  • Nystagmus - jerking movement of the eye
• Chronic ear infections
• Dental defects
• Poor tongue control
• Bluntly ended fingers, extra padding on the fingers and toes
• Elbow deformity
• Swelling of the extremities
• Pigmented nevi-birthmark

For unknown reasons, individuals with Noonan syndrome may be susceptible to an adverse reaction called malignant hypothermia, during anesthesia administration. Hence, extreme care should be taken to watch out for such complication, when anesthesia is given for surgery.

How is Noonan Syndrome Treated?

There is no specific treatment of Noonan Syndrome. The treatment is directed towards managing the specific signs and symptoms of the disorder.

• Growth hormones injections have been used successfully to treat short stature
• Some may need special accommodation in schools for speech, vision, and hearing difficulties
• Surgical correction of heart defects
• Surgery for cryptorchidism and to bring the testis into the scrotal sac
• Oral prosthetic surgery to correct dental deformities
• Treatment for heart failure with medications
• Speech therapy for speech difficulties
• Treatment for vision abnormalities such as cataract surgery
• Since the individuals have a tendency to bleed easily, aspirin and aspirin-containing products should be avoided
• Some individuals have higher frequency of UTIs, and hence antibiotic therapy may be necessary during such episodes

How can Noonan Syndrome be Prevented?

• Currently, there are no specific methods or guidelines to prevent Noonan Syndrome, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counselling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Noonan Syndrome? (Outcomes/Resolutions)

• Noonan syndrome is a lifelong disorder and the management of all associated complications is important to provide a better quality of life
• Severity of heart defects determine the life expectancy of an individual
• Most individuals with this syndrome have normal IQ

Additional and Relevant Useful Information for Noonan Syndrome:

There are voluntary organizations and support groups that provide help and understanding to the families and parents of the Noonan Syndrome disorder affected.