Makindo Medical Notes

Related Subjects: |Autosomal Dominant |Autosomal Recessive |X Linked Recessive

👩‍⚕️ Noonan syndrome is a genetic disorder first described by the American pediatric cardiologist Jacqueline Noonan. It affects both sexes and is one of the most common syndromic causes of congenital heart disease. Although most affected children live into adulthood with good quality of life, complications such as hypertrophic cardiomyopathy or bleeding disorders can be serious. It is sometimes nicknamed “Male Turner syndrome” because of overlapping physical features, though it has a completely different genetic basis.

📖 About

• Multisystem disorder characterised by dysmorphic facial features, short stature, cardiac anomalies, and variable developmental delay.
• Prevalence: ~1 in 2,500 live births 🌍.
• Both sexes equally affected (unlike Turner’s syndrome).
• Belongs to the group of conditions called RASopathies (caused by mutations in genes regulating the RAS/MAPK signalling pathway).

🧬 Aetiology & Genetics

• Inheritance: Autosomal dominant (50% recurrence risk if a parent is affected), though many cases arise de novo.
• Genes involved: Most commonly PTPN11 (≈50%), but also SOS1, RAF1, KRAS, NRAS, and others linked to RAS/MAPK pathway.
• Mutations cause abnormal intracellular signalling → disrupted cell growth, differentiation, and development.

🧍 Clinical Features

• Growth: Short stature (often becomes evident after age 2); delayed bone age.
• Facial Features: Broad forehead, triangular face, hypertelorism (wide-spaced eyes), ptosis (drooping eyelids), low-set posteriorly rotated ears, and webbed neck (pterygium colli).
• Cardiovascular ❤️:
  • Pulmonary valve stenosis (most common defect).
  • Hypertrophic cardiomyopathy (20–30%).
  • Atrial/ventricular septal defects and branch pulmonary artery stenosis.
• Developmental/Neurological 🧠: Hypotonia, delayed motor milestones, mild intellectual disability or learning difficulties (especially visuospatial and language).
• Haematological 🩸: Easy bruising, prolonged bleeding (e.g., factor XI deficiency, platelet dysfunction).
• Genitourinary: Cryptorchidism in males, delayed puberty.
• Other: Lymphoedema at birth, chest deformities (pectus excavatum/carinatum), scoliosis.

🔍 Differential Diagnosis

• Turner syndrome (45,X): Short stature, webbed neck, cardiac defects but restricted to females.
• Cardio-facio-cutaneous (CFC) syndrome: Also a RASopathy, but with more ectodermal findings (sparse hair, ichthyosis-like skin changes).
• Costello syndrome: Coarse facial features, papillomas, and greater cancer predisposition.
• Williams syndrome: Supravalvular aortic stenosis, characteristic "elfin" facies, hypercalcaemia.

🩺 Investigations

• Genetic testing: Confirms diagnosis (panel for RAS/MAPK mutations).
• Echocardiogram: Assess pulmonary stenosis, septal defects, hypertrophic cardiomyopathy.
• Clotting screen: Factor assays if bleeding tendency.
• Developmental assessment: Early intervention planning.
• Growth charts & endocrinology: Monitor stature and pubertal development.

⚕️ Management

• Cardiac Care: Surgical/balloon valvotomy for severe pulmonary stenosis; medical/surgical management of cardiomyopathy.
• Growth Hormone Therapy: May improve adult height in selected cases.
• Developmental Support: Early speech, occupational, and physical therapy. Special educational plans as needed.
• Haematology: Screen for coagulopathy before surgery or invasive procedures; manage with factor replacement or desmopressin if indicated.
• Cryptorchidism: Early orchidopexy to reduce infertility risk.
• Multidisciplinary Follow-up: Cardiology, endocrinology, haematology, genetics, developmental paediatrics.

📌 Prognosis

Most children with Noonan syndrome reach adulthood and live independently. Life expectancy is usually normal, but outcome depends on the severity of cardiac involvement and bleeding disorders. Surveillance is key, as progressive hypertrophic cardiomyopathy and severe pulmonary stenosis can be life-limiting.

📚 References

• Noonan Syndrome – GeneReviews (NCBI)
• Orphanet – Noonan Syndrome