From the Guidelines
Noonan syndrome is a genetic disorder characterized by distinctive facial features, short stature, heart defects, and other physical abnormalities, caused by mutations in several genes, most commonly PTPN11, which affects the RAS-MAPK signaling pathway important for cell growth and division. This condition is part of a group of syndromes known as RASopathies, which also include cardio-facio-cutaneous syndrome and Costello syndrome 1. People with Noonan syndrome typically have a triangular-shaped face, wide-set eyes, low-set ears, and a webbed neck. Heart defects, particularly pulmonary valve stenosis, are common, with approximately 50% of individuals having some form of congenital heart disease, including pulmonary valve stenosis, atrial septal defect, and hypertrophic cardiomyopathy 1.
Key Characteristics and Management
- Distinctive facial features, short stature, and heart defects are common characteristics of Noonan syndrome.
- Management involves a multidisciplinary approach with regular cardiac evaluations, growth monitoring, and developmental assessments.
- Growth hormone therapy may be prescribed for children with significant growth delays.
- Physical therapy, speech therapy, and educational support are often needed to manage symptoms and improve quality of life.
- The severity of Noonan syndrome varies widely between individuals, with some having mild symptoms and others requiring more intensive medical support.
Importance of Early Intervention
Early intervention and appropriate medical care can help manage symptoms and improve quality of life for individuals with Noonan syndrome. Regular monitoring and assessments are crucial to identify any potential complications early on, such as cardiac issues or developmental delays. With proper management, individuals with Noonan syndrome can lead active and fulfilling lives, despite the challenges posed by their condition 1.
From the Research
Definition and Characteristics of Noonan Syndrome
- Noonan syndrome (NS) is a mostly dominantly inherited disorder affecting 1:1000 to 1:2500 live births 2.
- 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 2.
- NS is characterized by a typical facial gestalt, congenital heart defects, variable cognitive deficits, skeletal defects, and short stature 3.
- The condition is caused by germline pathogenic variants in genes coding proteins with a role in the RAS/mitogen-activated protein kinase signaling pathway 3, 4, 5, 6.
Diagnosis and Management
- Diagnosis is based on a combination of features, including typical facial features, short stature, skeletal abnormalities, presence of cardiac defects, mild developmental delay, cryptorchidism, lymphatic dysplasia, and a family history of NS 2.
- Molecular testing should be performed to confirm the diagnosis in patients, with next-generation sequencing being the best choice for diagnostic testing due to the high number of genes associated with NS and other RASopathy disorders 6.
- A multidisciplinary approach provides the best care for patients with NS, and early recognition of NS and referral to an appropriate specialist is important 2.
- Management recommendations include management of growth and development, with data on growth hormone treatment efficacy showing a modest response in height gains 5.
Clinical Variability and Genetic Heterogeneity
- NS is a clinically and genetically heterogeneous condition, with variable expressivity and a changing phenotype with age, affecting multiple organs and systems 4, 5.
- The genetic heterogeneity of NS means that treatment with rhGH should be personalized, and a conservative approach with judicious surveillance is recommended 3.
- Patients with NS also have a higher risk for leukemia and specific solid tumors, and age-specific guidelines for the management of NS are available 6.