Summary
Definition
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.
História e exame físico
Principais fatores diagnósticos
- 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
Outros fatores diagnósticos
- abnormalities identified prenatally
- chest deformity
- developmental delay/learning difficulty
- skeletal anomalies
- muscle weakness
- history of renal malformation
Fatores de risco
- family history of NS
- advanced paternal age
Investigações diagnósticas
Primeiras investigações a serem solicitadas
- ECG
- echocardiogram
Investigações a serem consideradas
- CBC
- coagulation profile
- molecular genetic testing
- abdominal ultrasound
- renal ultrasound
Algoritmo de tratamento
all patients
Colaboradores
Autores
David A. Stevenson, MD
Associate Professor
Department of Pediatrics
Division of Medical Genetics
Stanford University
Stanford
CA
Declarações
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.
Agradecimentos
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
Liliana N. Contreras, MD
Chief
Endocrine Research Department
Instituto de Investigaciones Médicas Alfredo Lanari
IDIM-CONICET
University of Buenos Aires
Argentina
Declarações
LNC declares that she has no competing interests.
Bruce Gelb, MD
Professor of Pediatrics
Mount Sinai School of Medicine
New York
NY
Declarações
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
Declarações
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.
Referências
Principais artigos
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 Resumo
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 Resumo
Allanson JE. Noonan syndrome. J Med Genet. 1987 Jan;24(1):9-13.Texto completo Resumo
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. Resumo
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. Resumo
Romano AA, Allanson JE, Dahlgren J, et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics. 2010 Oct;126(4):746-59. Resumo
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. Resumo
Artigos de referência
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Diagnósticos diferenciais
- Turner syndrome
- LEOPARD syndrome
- Cardio-facio-cutaneous syndrome
Mais Diagnósticos diferenciaisDiretrizes
- Noonan syndrome: clinical features, diagnosis, and management guidelines
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