This report describes general characteristics of the group of diseases classified as Noonan syndrome. Noonan syndrome is a genetically heterogeneous disorder, with multiple genes and mapped loci. A listing of Noonan syndrome subtypes, as defined by OMIM, may be found in the table below, with links to more detailed reports for subtypes that have been investigated using fly models.
[updated May 2015 by FlyBase; FBrf0222196]
Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, facial dysmorphism, and a wide spectrum of congenital heart defects. The distinctive facial features consist of a broad forehead, hypertelorism, downslanting palpebral fissures, a high-arched palate, and low-set, posteriorly rotated ears. Cardiac involvement is present in up to 90% of patients. Pulmonic stenosis and hypertrophic cardiomyopathy are the most common forms of cardiac disease, but a variety of other lesions are also observed. Additional relatively frequent features include multiple skeletal defects (chest and spine deformities), webbed neck, mental retardation, cryptorchidism, and bleeding diathesis (summary by Tartaglia et al., 2002 pubmed:11992261). [from OMIM:163950, 2015.04.14]
Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. [Gene Reviews, Noonan Syndrome, 2020.08.21]
Noonan syndrome is a genetically heterogeneous disorder. [from OMIM:163950, 2015.04.14]
Noonan syndrome is most often inherited in an autosomal dominant manner. While many individuals with autosomal dominant NS have a de novo pathogenic variant, an affected parent is recognized in 30-75% of families. [Gene Reviews, Noonan Syndrome, 2020.08.21]