Noonan syndrome

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Noonan Syndrome (NS) is a relatively common congenital genetic condition which affects both males and females equally[1]:550 . It used to be referred to as the male version of Turner’s syndrome[2]; however, the genetic causes of Noonan syndrome and Turner syndrome are distinct. The principal features include congenital Heart Malformation, short stature, learning problems, indentation of the chest, impaired blood clotting, and a characteristic configuration of facial features. The syndrome is named after Dr Jacqueline Noonan.

It is believed that between approximately 1 in 1,000 and 1 in 2,500 children worldwide are born with NS. It is one of the most common genetic syndromes associated with congenital heart disease, similar in frequency to Down syndrome. However, the range and severity of features can vary greatly in patients with NS. Therefore, the syndrome is not always identified at an early age.

Recurrence in siblings and apparent transmission from parent to child has long suggested a genetic defect with autosomal dominant inheritance and variable expression. A person with NS has up to a 50% chance of transmitting it to a child. The fact that an affected parent is not always identified for children with NS suggests several possibilities:

In most of the families with multiple affected members, NS maps to chromosome 12q24.1. In 2001, it was reported that approximately half of a group of patients with Noonan syndrome carried a mutation of the PTPN11 gene at that location, which encodes protein tyrosine phosphatase SHP-2.[3] The SHP2 protein is a component of several intracellular signal transduction pathways involved in embryonic development that modulate cell division, differentiation, and migration, including that mediated by the epidermal growth factor receptor. The latter pathway is important in the formation of the cardiac semilunar valves. It has recently been shown that activating mutations in SOS1 also give rise to NS.[4] Shp2 and SOS1 both have roles as positive regulators of the Ras/MAP kinase pathway suggesting that dysregulation of this pathway may play a major role in the genesis of this syndrome.[5] Additional mutations in KRAS [6] and RAF1[7] genes have been reported to cause Noonan syndrome in a smaller percentage of individuals with the syndrome. Chromosomal abnormalities, such as a duplication of chromosome region 12q24 encompassing gene PTPN11 can result in an apparent Noonan syndrome[8].

The most prevalent (common) signs are highlighted in bold with frequency listed in parentheses.

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