Noonan syndrome

Noonan syndrome (NS) is a relatively common genetic disorder characterized by distinctive facial features, short stature, congenital heart defects, and developmental variability. It is sometimes referred to as Turner-like syndrome due to phenotypic overlap with Turner syndrome, though it affects both males and females and involves a different genetic basis. Noonan syndrome belongs to a group of conditions known as RASopathies, caused by germline mutations in genes encoding components or regulators of the RAS/MAPK signaling pathway. The most commonly mutated gene is PTPN11 (accounting for approximately 50% of cases), with other causative genes including SOS1, RAF1, RIT1, KRAS, NRAS, BRAF, MAP2K1, MRAS, and LZTR1, among others. The condition affects multiple body systems. Characteristic craniofacial features include a broad forehead, hypertelorism (widely spaced eyes), down-slanting palpebral fissures, low-set posteriorly rotated ears, and a short or webbed neck. Congenital heart disease is present in 50–80% of individuals, with pulmonary valve stenosis being the most common cardiac defect, followed by hypertrophic cardiomyopathy and atrial septal defects. Short stature is observed in many affected individuals, often falling below the third percentile without growth hormone treatment. Other features may include chest deformities (pectus excavatum or carinatum), cryptorchidism in males, lymphatic dysplasia, bleeding diatheses due to various coagulation factor deficiencies or platelet dysfunction, and mild intellectual disability or learning difficulties in some individuals. Management of Noonan syndrome is multidisciplinary and symptom-based. Growth hormone therapy has been approved in several countries for the treatment of short stature associated with Noonan syndrome. Cardiac defects may require surgical or catheter-based intervention. Developmental support, including speech therapy and educational accommodations, is often beneficial. Hematologic abnormalities should be evaluated prior to any surgical procedures. Regular monitoring by a team including cardiologists, endocrinologists, and developmental specialists is recommended. Emerging targeted therapies directed at the RAS/MAPK pathway, such as MEK inhibitors, are under investigation, particularly for severe manifestations like hypertrophic cardiomyopathy.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Noonan syndrome