From the Guidelines
Noonan syndrome is a genetic disorder characterized by distinct facial features, short stature, and congenital heart disease, affecting approximately 80% of individuals with the condition.
Clinical Features and Genetic Abnormalities
The syndrome is caused by mutations in several genes, including PTPN11, KRAS, SOS1, RAF1, NRAS, BRAF, and MAP2K1 1. Common clinical features of Noonan syndrome include:
- Facial anomalies
- Webbed neck
- Chest deformity
- Short stature
- Lymphatic abnormalities
- Bleeding abnormalities
Common Cardiac Findings
Individuals with Noonan syndrome often have congenital heart disease, with common findings including:
- Pulmonary stenosis (PS)
- Atrial septal defect (ASD)
- Hypertrophic cardiomyopathy (HCM) 1
Genetic Counseling and Testing
Genetic counseling and testing are essential for individuals with Noonan syndrome, as they can help identify asymptomatic at-risk family members and enable preemptive screening and treatment of complications such as hypertrophic cardiomyopathy 1.
Cancer Risk
Individuals with Noonan syndrome are also at an increased risk of cancer, particularly certain types of pediatric cancer, and should be monitored accordingly 1.
From the Research
Definition and Characteristics of Noonan Syndrome
- Noonan syndrome (NS) is a genetic condition characterized by short stature, congenital heart defects, and distinctive facial features 2, 3, 4, 5, 6.
- It is a clinically and genetically heterogeneous condition, with variable expressivity and a changing phenotype with age, affecting multiple organs and systems 2, 4.
Clinical Features and Diagnosis
- The phenotype varies in severity and can involve multiple organ systems over a patient's lifetime, including typical facial features, short stature, skeletal abnormalities, presence of cardiac defects, mild developmental delay, cryptorchidism, lymphatic dysplasia, and a family history of NS 3, 5.
- Diagnosis is based on a combination of clinical features, and molecular genetic testing can confirm diagnosis in a significant percentage of cases 3, 4, 5, 6.
- Early, accurate diagnosis is important for individualized management and to optimize developmental and long-term outcomes 3.
Genetic Basis and Related Conditions
- NS is caused by mutations in genes encoding proteins of the RAS-MAPKinases pathway, and is part of a group of conditions collectively termed "RASopathies" 2, 6.
- NS shares clinical features with other rare conditions, including LEOPARD syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair, and Costello syndrome 4, 6.
Management and Treatment
- A multidisciplinary approach provides the best care for patients with NS, and age-based NS-specific growth charts and treatment guidelines are available 3, 5.
- Data on growth hormone treatment efficacy are sparse, and show a modest response in height gains, similar to that observed in Turner syndrome 2.
- Patients with NS also have a higher risk for leukemia and specific solid tumors, and require regular follow-up care 6.