What is Noonan Syndrome?
Noonan syndrome is a genetic condition that happens in 1 in 1,000 to 1 in 2,500 live births.
Common features of the condition include congenital heart disease, short height, distinctive facial features, bleeding disorders and learning disabilities. While these features are common, not all of them are seen in every patient. The presentation is variable, and a person with Noonan syndrome may not have every feature.
Management of a patient with Noonan syndrome is specific to the individual.
What are Some of the Features of Noonan Syndrome?
Cardiac Features
About 50-80% of people with Noonan syndrome have a congenital heart defect. The most common heart defect seen is pulmonary valve stenosis, which is a narrowing in the valve attached to the blood vessel that carries blood out of the heart to the lungs. Other types of congenital heart defects are also seen in patients with Noonan syndrome, including septal defects (“hole in the heart”) and Tetralogy of Fallot.
Hypertrophic cardiomyopathy, a heart muscle disease, is found in around 20% of patients with Noonan syndrome. This may be present at birth or develop later.
Non-Cardiac Features
Endocrine
Many people with Noonan syndrome have short stature. It is common for height and weight to be below the third percentile on a typical growth chart.
Puberty often happens later in individuals with Noonan syndrome.
Bleeding Disorders
Some people have bleeding disorders, mainly problems with the way their blood clots. Mild symptoms may include easy bruising or heavy menstrual cycles in women. Identifying bleeding disorders is important, because problems with clotting should be known before any surgery.
Learning and Development
Delay in reaching early developmental milestones is common for people with Noonan syndrome. Feeding problems are also common during infancy.
Around 25% of people have learning disabilities, and some require a special education classroom setting. The average IQ tends to be lower than other family members who do not have Noonan syndrome.
Physical Features
People with Noonan syndrome have similar characteristic facial features that tend to change over time. The facial features can be more subtle and may be hardest to recognize in an adult with Noonan syndrome. Although they share many facial features, individuals with Noonan syndrome also resemble their own family members.
Patients with Noonan syndrome may have a broad or webbed neck.
Differences in the structure of the breast bone, located in the center of the chest, are often seen in patients with Noonan syndrome.
Other Features
Most people with Noonan syndrome have some type of eye and/or vision problem. A much smaller percentage may have some degree of hearing loss.
Around 10% of people have a kidney anomaly. These are typically mild and have little clinical significance. Having a structural kidney problem may make urinary tract infections more likely.
How is Noonan Syndrome Diagnosed?
The diagnostic evaluation for Noonan syndrome should be done by an experienced physician. This evaluation should include a detailed family history, medical history and physical examination. A diagnosis can be made based on observed clinical features by a physician familiar with Noonan syndrome.
Genetic testing is also useful in making a diagnosis. Currently, around 60-70% of patients have an identifiable mutation in one of several genes that are known to cause Noonan syndrome. On the other hand, about 30-40% of people with Noonan syndrome do not have an identifiable gene mutation. So their diagnosis is made based on clinical features alone.
Typically, every person has two copies of each gene in their genetic make-up. One is inherited from their father, and the other from their mother. Noonan syndrome is an autosomal dominant condition. This means a change in only one copy of a gene known to cause the condition is enough to cause the observed features. The condition affects males and females equally. A person with Noonan syndrome has a 50% chance of passing on the condition to each of their children. Children who inherit Noonan syndrome may be more or less severely affected than their parent with Noonan syndrome.
People with Noonan syndrome who do not have an identifiable gene mutation likely have the same risks for passing on the condition as those who have a proven genetic cause for their condition.
Noonan syndrome is part of a group of related disorders caused by changes in genes linked with the Ras/MAPK pathway. This pathway is involved in several important cell functions, including:
- the growth and division of cells (proliferation)
- the process where cells mature to carry out specific functions (differentiation)
- cell movement (migration)
- the self-destruction of cells (apoptosis)
Genetic syndromes caused by changes in genes of the Ras/MAPK pathway are called RASopathies. Conditions in this group include Noonan syndrome, Noonan syndrome with multiple lentigines, Costello syndrome, cardiofaciocutaneous syndrome and neurofibromatosis among others. These conditions share many of the same features, so genetic testing can be an important tool to confirm a specific diagnosis.
How is Noonan Syndrome Treated and Managed?
There is no “cure” for Noonan syndrome, but several interventions and therapies are available. Management is tailored to each patient, based on their specific clinical features.
For people who have heart features, cardiac care is similar to patients who have the same heart defect but don’t have Noonan syndrome. People with Noonan syndrome who do not have cardiac features should be re-evaluated at least every five years, as some heart features may develop later in life. Adults with Noonan syndrome are recommended to continue with cardiac screening as well.
Early intervention services—including physical, occupational and/or speech therapy—may be recommended for patients with delayed development.
Growth hormone supplementation is an option for people with short stature. Patients on growth hormone are followed by an endocrinologist.
People with bleeding disorders should be followed by a specialist called a hematologist. Medication may be given to reduce the risk for abnormal bleeding.
Other specialists may be involved in the care of people with Noonan syndrome, depending on the specific complications or symptoms.
What is the Prognosis for Patients with Noonan Syndrome?
Noonan syndrome is a lifelong disorder. Identification and treatment of all associated medical complications is important. Prognosis in terms of life expectancy generally depends on the severity of any heart defect.
