Resumen
Definición
Noonan syndrome (NS) is a relatively common, autosomal-dominant, inherited disorder that is predominantly characterized by short stature, subtle facial dysmorphisms, chest deformity, congenital heart disease, and variable degrees of developmental delay.[1] Coagulation defects, cryptorchidism in men, and lymphatic dysplasia are not uncommon.[Figure caption and citation for the preceding image starts]: Boy (6 years of age) with Noonan syndromeFrom the collection of Judith E. Allanson [Citation ends].
The syndrome is thought to be caused primarily by gain-of-function (activating) mutations in genes in the Ras/mitogen-activated protein kinase (MAPK) signal transduction pathway.[2][3][4][5][6][7][8][9][10] Genes implicated include: PTPN11, SOS1, RAF1, RIT1, RASA2, LZTR1, SOS2, CBL, KRAS, NRAS, BRAF, PPP1CB, and MAP2K1. The most commonly identified genetic mutation involves PTPN11.[2][11][12]
Noonan syndrome caused by SHOC2 mutation is now considered by most to be an overlapping condition with unusual features (loose anagen hair); some consider it to be a distinct condition, while others consider it to be classified only as Noonan syndrome.
Anamnesis y examen
Principales factores de diagnóstico
- positive family history
- short stature
- dysmorphic facial features
- cryptorchidism
- cardiac anomalies
- delayed puberty
- easy bruising or bleeding
- lymphedema
- pigmentary anomalies
- sparse or absent eyebrows and lashes
- splenomegaly
Otros factores de diagnóstico
- abnormalities identified prenatally
- chest deformity
- developmental delay/learning difficulty
- skeletal anomalies
- muscle weakness
- history of renal malformation
Factores de riesgo
- family history of NS
- advanced paternal age
Pruebas diagnósticas
Primeras pruebas diagnósticas para solicitar
- ECG
- echocardiogram
Pruebas diagnósticas que deben considerarse
- CBC
- coagulation profile
- molecular genetic testing
- abdominal ultrasound
- renal ultrasound
Algoritmo de tratamiento
all patients
Colaboradores
Autores
David A. Stevenson, MD
Associate Professor
Department of Pediatrics
Division of Medical Genetics
Stanford University
Stanford
CA
Divulgaciones
DAS has acted as a consultant for Lineagen, GLG, and Alexion, and has given expert testimony. He is on the medical advisory board for parents' support groups for Costello syndrome and CFC syndrome. DAS is an author of a reference cited in this topic. DAS has also been reimbursed by RASopathies Network for attending conferences.
Agradecimientos
Dr David A. Stevenson would like to gratefully acknowledge Dr Judith E. Allanson, the previous contributor to this topic. JEA is an author of a number of references cited in this topic.
Revisores por pares
Liliana N. Contreras, MD
Chief
Endocrine Research Department
Instituto de Investigaciones Médicas Alfredo Lanari
IDIM-CONICET
University of Buenos Aires
Argentina
Divulgaciones
LNC declares that she has no competing interests.
Bruce Gelb, MD
Professor of Pediatrics
Mount Sinai School of Medicine
New York
NY
Divulgaciones
BG received royalties from GeneDx, Correlegan, Preventative Genetics, Baylor College of Medicine, and Harvard Medical School/Partners for genetic testing of Noonan syndrome. BG is an author of a number of references cited in this topic.
Jacqueline Noonan, MD
Professor Emeriti
Department of Pediatrics
College of Medicine
University of Kentucky
Lexington
KY
Divulgaciones
JN is on the Noonan Syndrome Advisory Board for Novo Nordisk and has received payment for speaking at a symposium. JN is an author of a number of references cited in this topic.
Agradecimiento de los revisores por pares
Los temas de BMJ Best Practice se actualizan de forma continua de acuerdo con los desarrollos en la evidencia y en las guías. Los revisores por pares listados aquí han revisado el contenido al menos una vez durante la historia del tema.
Divulgaciones
Las afiliaciones y divulgaciones de los revisores por pares se refieren al momento de la revisión.
Referencias
Artículos principales
Jorge AA, Malaquias AC, Arnhold IJ, et al. Noonan syndrome and related disorders: a review of clinical features and mutations in genes of the RAS/MAPK pathway. Horm Res. 2009;71(4):185-93.Texto completo Resumen
Shaw AC, Kalidas K, Crosby AH, et al. The natural history of Noonan syndrome: a long-term follow-up study. Arch Dis Child. 2007 Feb;92(2):128-32.Texto completo Resumen
Allanson JE. Noonan syndrome. J Med Genet. 1987 Jan;24(1):9-13.Texto completo Resumen
Lee DA, Portnoy S, Hill P, et al. Psychological profile of children with Noonan syndrome. Dev Med Child Neurol. 2005 Jan;47(1):35-8. Resumen
Ishizawa A, Oho S, Dodo H, et al. Cardiovascular abnormalities in Noonan syndrome: the clinical findings and treatments. Acta Paediatr Jpn. 1996 Feb;38(1):84-90. Resumen
Romano AA, Allanson JE, Dahlgren J, et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics. 2010 Oct;126(4):746-59. Resumen
Raaijmakers R, Noordam C, Karagiannis G, et al. Response to growth hormone treatment and final height in Noonan syndrome in a large cohort of patients in the KIGS database. J Pediatr Endocrinol Metab. 2008 Mar;21(3):267-73. Resumen
Artículos de referencia
Una lista completa de las fuentes a las que se hace referencia en este tema está disponible para los usuarios con acceso a todo BMJ Best Practice.
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Más DiferencialesGuías de práctica clínica
- Noonan syndrome: clinical features, diagnosis, and management guidelines
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