Noonan syndrome

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 ¹¹¹⁰. 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
  • mental retardation
  • 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 ⁴³
  • hypertrophic cardiomyopathy ^4,53,4: thought to affect ~20% of individuals ⁴³
  • patent ductus arteriosus (PDA)

• vascular

  • congenital lymphovascular abnormalities
    • cystic hygroma
    • lymphoedema ⁶⁵
    • lymphangiectasia(e) ³²

• generalised musculoskeletal

  • short stature

  • hypotonia

  • delayed sternal ossification ⁸⁷

• renal anomalies
  • dilated renal pelvices ^7,106,9

Pathology

Genetics

The inheritance is autosomal dominant although a significant proportion of cases are sporadic ⁹⁸. 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 signalling of the Ras/MAPK pathway. However. other genes that may be less commonly implicated including SOS1, KRAS, RAF1, NRAS, and SHOC2 ¹¹¹⁰. Because of its effect in amplifying the Ras/MAPK pathway, it is considered to be a RASopathy ¹¹¹⁰.

Radiographic features

Antenatal ultrasound

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

History and etymology

It is named after Jacqueline A Noonan (1928--fl 2019), an American paediatric cardiologist ¹¹¹.