Noonan syndrome is a relatively common, autosomal-dominant inherited disorder.
Characteristic phenotype includes short stature, chest deformity, congenital heart defects, and unusual facial features.
Boys frequently present with cryptorchidism and manifest delayed puberty.
Caused by activating mutations in multiple genes in the Ras/mitogen-activated protein kinase (MAPK) signal transduction pathway. The most commonly implicated gene is PTPN11.
Treatment focuses on the individual symptom, and may include surgery for undescended testes in boys, optimisation of cardiac function, and growth hormone treatment for short stature.
The majority of patients lead normal lives. Prognosis is largely dependent on the type and severity of cardiac disease, which may occur in 50% to 80% of cases.
Noonan syndrome (NS) is a relatively common, autosomal-dominant inherited disorder that is predominantly characterised by short stature, subtle facial dysmorphisms, chest deformity, congenital heart disease, and variable degrees of developmental delay. Coagulation defects, cryptorchidism in men, and lymphatic dysplasia are not uncommon.
The syndrome is thought to be caused primarily by gain-of-function (activating) mutations in genes in the Ras/mitogen-activated protein kinase (MAPK) signal transduction pathway. Genes implicated include: PTPN11, SOS1, RAF1, RIT1, RASA2, LZTR1, SOS2, CBL, KRAS, NRAS, BRAF, PPP1CB, and MAP2K1. The most commonly identified genetic mutation involves PTPN11.
Noonan syndrome caused by SHOC2 mutation is now considered by most to be an overlapping condition with unusual features (e.g., loose anagen hair); some consider it to be a distinct condition, while others consider it to be classified only as Noonan syndrome.
History and exam
Key diagnostic factors
- positive family history
- short stature
- dysmorphic facial features
- cardiac anomalies
- delayed puberty
- easy bruising or bleeding
- pigmentary anomalies
- sparse or absent eyebrows and lashes
Other diagnostic factors
- abnormalities identified antenatally
- chest deformity
- developmental delay/learning difficulty
- skeletal anomalies
- muscle weakness
- historyof renal malformation
- family history of NS
- advanced paternal age
1st investigations to order
Investigations to consider
- coagulation profile
- molecular genetic testing
- abdominal ultrasound
- renal ultrasound
- Turner syndrome
- LEOPARD syndrome
- Cardio-facio-cutaneous syndrome
- Noonan syndrome: clinical features, diagnosis, and management guidelines
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