Noonan-Syndrom

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Noonan syndrome (NS) is a genetically and phenotypically heterogeneous non-aneuploidic congenital RASopathy. Affected individuals can bear some clinical features similar to that of Turner syndrome.

Epidemiology

The estimated incidence is at ~1 in 1000-2500 . As individuals have normal number of chromosomes, both males and females can be affected.

Clinical presentation

An immense number of clinical features have been described which can be present at varying degrees. These include:

craniofacial
- telecanthus, hypertelorism
- low-set ears, rotated ears +/- thickened helix
- epicanthus
- facial asymmetry
- intellectual disability
- microgenia
- low neck hairline
cervicothoracic
- pterigium colli: webbed neck
- winged scapulae
- pectus excavatum
- pectus carinatum
cardiopulmonary
- pulmonary stenosis (with dysplastic pulmonary valve): most common cardiac anomaly
- hypertrophic cardiomyopathy : thought to affect ~20% of individuals
- patent ductus arteriosus (PDA)
vascular
- congenital lymphovascular abnormalities
generalized musculoskeletal
- short stature
- hypotonia
- delayed sternal ossification
renal anomalies
- dilated renal pelvices

Pathology

Genetics

The inheritance is autosomal dominant although a significant proportion of cases are sporadic. Many genes have been implicated, the most common being the PTPN11 gene which encodes for SHP2, which results in an inability to inactivate SHP2 causing increased signaling of the Ras/MAPK pathway. However. other genes that may be less commonly implicated including SOS1, KRAS, RAF1, NRAS, and SHOC2 . Because of its effect in amplifying the Ras/MAPK pathway, it is considered to be a RASopathy .

Radiographic features

Antenatal ultrasound

Early 1 trimester ultrasound may show nuchal edema or a cystic hygroma similar to that of Turner syndrome. With subsequent scanning, some of the above individual clinical features may be present sonographically.