Noonan syndrome
Резюме
Определение
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.
Анамнез и осмотр
Ключевые диагностические факторы
- 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
Другие диагностические факторы
- abnormalities identified prenatally
- chest deformity
- developmental delay/learning difficulty
- skeletal anomalies
- muscle weakness
- history of renal malformation
Факторы риска
- family history of NS
- advanced paternal age
Диагностические исследования
Исследования, которые показаны в первую очередь
- ECG
- echocardiogram
Исследования, проведение которых нужно рассмотреть
- CBC
- coagulation profile
- molecular genetic testing
- abdominal ultrasound
- renal ultrasound
Алгоритм лечения
all patients
Составители
Авторы
David A. Stevenson, MD
Associate Professor
Department of Pediatrics
Division of Medical Genetics
Stanford University
Stanford
CA
Раскрытие информации
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.
Выражение благодарностей
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.
Рецензенты
Liliana N. Contreras, MD
Chief
Endocrine Research Department
Instituto de Investigaciones Médicas Alfredo Lanari
IDIM-CONICET
University of Buenos Aires
Argentina
Раскрытие информации
LNC declares that she has no competing interests.
Bruce Gelb, MD
Professor of Pediatrics
Mount Sinai School of Medicine
New York
NY
Раскрытие информации
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
Раскрытие информации
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.
Peer reviewer acknowledgements
BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.
Disclosures
Peer reviewer affiliations and disclosures pertain to the time of the review.
Список литературы
Основные статьи
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.Полный текст Аннотация
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.Полный текст Аннотация
Allanson JE. Noonan syndrome. J Med Genet. 1987 Jan;24(1):9-13.Полный текст Аннотация
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. Аннотация
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. Аннотация
Romano AA, Allanson JE, Dahlgren J, et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics. 2010 Oct;126(4):746-59. Аннотация
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. Аннотация
Статьи, указанные как источники
A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
Отличия
- Turner syndrome
- LEOPARD syndrome
- Cardio-facio-cutaneous syndrome
Больше ОтличияРекомендации
- Noonan syndrome: clinical features, diagnosis, and management guidelines
Больше Рекомендации
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