Noonan syndrome

Last revised by Mostafa Elfeky on 27 Dec 2021

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

The estimated incidence is at ~1 in 1000-2500 10. As individuals have normal number of chromosomes, both males and females can be affected.  

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

The inheritance is autosomal dominant although a significant proportion of cases are sporadic 8. 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 include SOS1KRASRAF1NRAS, and SHOC2 10. Because of its effect in amplifying the Ras/MAPK pathway, it is considered to be a RASopathy 10.

Early 1st 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.

It is named after Jacqueline A Noonan (1928-fl 2019), an American pediatric cardiologist 11.

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