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Noonan Syndrome.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
2001 Nov 15 [updated 2016 Feb 25].

Author information

1
Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
2
Cardiovascular Genetics, Children’s Hospital Boston, Boston, Massachusetts

Excerpt

CLINICAL CHARACTERISTICS:

Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. 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. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one fourth of affected individuals have mild intellectual disability, and language impairments in general are more common in NS than in the general population.

DIAGNOSIS/TESTING:

NS is diagnosed on clinical grounds by observation of key features. Affected individuals have normal chromosome studies. Molecular genetic testing identifies a pathogenic variant in PTPN11 in 50% of affected individuals, SOS1 in approximately 13%, RAF1 and RIT1 each in 5%, and KRAS in fewer than 5%. Other genes in which pathogenic variants have been reported to cause Noonan syndrome in fewer than 1% of cases include NRAS, BRAF, and MAP2K1. Several additional genes associated with a Noonan-syndrome-like phenotype in fewer than ten individuals have been identified.

MANAGEMENT:

Treatment of manifestations: Cardiovascular anomalies in NS are usually treated as in the general population. Developmental disabilities are addressed by early intervention programs and individualized education strategies. Treatment for serious bleeding is guided by knowledge of the specific factor deficiency or platelet aggregation anomaly. Growth hormone (GH) treatment increases growth velocity. Surveillance: Monitoring of anomalies found in any system, especially cardiovascular abnormalities.

GENETIC COUNSELING:

NS is inherited in an autosomal dominant manner. Although many individuals with NS have a de novo pathogenic variant, an affected parent is recognized in 30%-75% of families. The risk to sibs of a proband depends on the genetic status of the parents. If a parent is affected, the risk is 50%. When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low (<1%). Each child of an individual with Noonan syndrome has a 50% chance of inheriting the pathogenic variant. Prenatal testing is possible if the NS-related pathogenic variant has been identified in an affected family member.

Copyright © 1993-2017, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

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