Manifestations of Noonan Syndrome
It is estimated that 50-80 percent of individuals 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 percent of patients with Noonan syndrome. This may be present at birth or develop later.
Many individuals 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 is often delayed in individuals with Noonan syndrome.
Some individuals are found to have bleeding disorders, mainly problems with the way their blood clots. Mild symptoms may include easy bruising or heavy menstrual cycles in women. Identification is important, as issues with clotting should be recognized before any surgical procedure.
Learning and Development
Delay in reaching early developmental milestones is common for individuals with Noonan syndrome. Feeding difficulties are also common during infancy.
Around 25 percent of individuals 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.
Individuals 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 structure of the breast bone, located in the center of the chest, are often seen in patients with Noonan syndrome.
Most individuals 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 percent of individuals 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.
Diagnosis and Genetics of Noonan Syndrome
The diagnostic evaluation for Noonan syndrome should be performed by an experienced physician. This evaluation should include a detailed family history, medial history, and physical examination. A diagnosis can be made on the basis of observed clinical features by a physician familiar with Noonan syndrome.
Genetic testing is also useful in making a diagnosis. Currently, around 60-70 percent of patients have an identifiable mutation in one of several genes which are known to cause Noonan syndrome. On the other hand, roughly 30-40 percent of individuals do not have an identifiable gene mutation. Thus, 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. An individual with Noonan syndrome has a 50 percent, or one in two chance, of passing on the condition to each of their children. Noonan syndrome is a variable condition. Children who inherit Noonan syndrome may be more or less severely affected than their parent with Noonan syndrome.
Individuals with Noonan syndrome who do not have an identifiable gene mutation likely have the same risks for recurrence 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 referred to as 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 characteristic features including cardiac issues. It can be difficult to confirm a specific diagnosis, and genetic testing can be an important tool for confirming a specific diagnosis.
Treatment and Management
There is no “cure” for Noonan syndrome, but several interventions and therapies are available. Management is individually tailored to each patient, based on their specific clinical features.
For individuals who have heart features, cardiac care is similar to patients who have the same heart defect but don’t have Noonan syndrome. Individuals 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 an individual with delayed development.
Growth hormone supplementation is an option for individuals with short stature. Individuals on growth hormone are followed by an endocrinologist.
Individuals 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 individuals with Noonan syndrome, depending on the specific complications or symptoms of that person.
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 the heart defect.
Noonan Syndrome Resources
The Noonan Syndrome Foundation
Article including guidelines on the management of individuals with Noonan syndrome:
Alicia A. Romano, Judith E. Allanson, Jovanna Dahlgren, et al. Noonan Syndrome: Clinical Features, Diagnosis, and Management Guidelines. Pediatrics 2010 126: 746-759.
The Cardiovascular Genetics Clinic in the Heart Institute at Cincinnati Children’s consists of cardiologists, geneticists, and genetic counselors who specialize in the care of individuals with Noonan syndrome and other genetic conditions with cardiac involvement. Learn more about this clinic and get contact information.