Noonan Syndrome

Noonan syndrome is a genetic RASopathy with multiple congenital abnormalities due to germline mutation involving the RAS/MAPK (mitogen-activated protein kinase) signaling pathway with variable penetrance.

 

However,Karyotype is normal, but must be done to exclude other genetic differentials.

 

Molecular genetic testingis can provide diagnostic confirmation but negative result does not exclude NS.

 

Due to similar phenotype, this condition is erroneously called ‘Pseudo- Turner’.

Autosomal Dominant condition, affects males and females with 50% chance of passing on to children.

 

 

Antenatal scans

May show non-specific changes such as increased nuchal translucency, polyhydramnios, hydrops or cystic hygroma.

 

 

 

 

Phenotypic appearances

– These may be absent at birth or show (Turners-like) widely set eyes, low-set ears, relatively large head, short-webbed neck, low posterior hairline, depressed nasal bridge, renal anomalies or short stature.

– Young children have global developmental delay and poor growth.

– Older children show characteristic webbed neck, large forehead, droopy eyelids with epicanthic folds, hypertelorism and low-set ears.

– Broad chest with widely spaced nipples and cubitus valgus.

– Learning and behavioural difficulties are common in school age.

– Congenital heart defects like Pulmonary stenosis, Hypertrophic cardiomyopathy or Coarctation of Aorta.

– Boys may show Cryptorchidism with increased risk of infertility.

– Squint and hearing issues are common.

– Lymphoedema can develop in limbs and chest-wall deformities like pectus are common.

– Easy bruising is common due to clotting factor or Platelet disorder.

 

 

Investigations for suspected Noonans

– Karyotype to exclude other genetic causes & Molecular test

– ECHO and ECG

– Hearing and vision assessment

– Renal tract ultrasound

– Coagulation profile for coagulopathies

 

 

Management

– Genetic counseling and supportive care for issues identified

– Provide information and signpost to disease specific patient groups

– Early intervention by therapy teams to promote development

– Cardiac defects require appropriate management or monitoring. Repeat ECHO every 5 years even if no cardiac defect known

– Growth hormone may be required to achieve optimal adult height

– Orchidopexy may be indicated at around 12 months age