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Noonan's syndrome
Male phenotype of Turner's syndrome.
Etiology: may occur in association with neurofibromatosis
Epidemiology:
- male:female ratio 1:1
- common, 1 in 1000-2500 live births
Pathology:
1) congenital heart disease
a) pulmonary valvular stenosis
b) cardiomyopathy, generally hypertrophic
c) SOS1 mutations engender a high prevalence of
- pulmonary valve disease
- atrial septal defects are less common
c) elevated central venous pressure
d) prominent a wave
e) late-peaking systolic murmur
2) pigeon breast (pes excavatum)
3) webbing of neck
4) antimongoloid slanting of palpebrae
5) cryptorchidism
Genetics:
- genetically heterogeneous
- type 4: autosomal dominant, involves SOS1 gene
- defects in neurofibromin when associated with neurofibromatosis
- type 3: autosomal dominant, associated with defects in KRAS
- type 1: autosomal dominant, associated with defects in PTPN11
- associated with defects in BRAF
- genes notes in CPT panel [6]
- BRAF, CBL, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, PTPN11, RAF1, RIT1, SHOC2, SOS1
- other genes: MEK1
Clinical manifestations:
- dysmorphic facial features
- neck webbing
- low hairline
- short stature
- hypertelorism
- cardiac anomalies
- deafness
- motor delay
- bleeding diathesis
- renal malformation
- pubertal delay, cryptorchidism
- developmental or behavioral problems
- vision problems, hearing loss
- lymphedema
- most patients are intellectually normal as adults [6]
Laboratory:
- Noonan syndrome genomic sequence analysis
- RAF1 gene mutation
- see ARUP consult [7]
Special laboratory:
- echocardiogram
- pulmonary valve stenosis +/- pulmonary regurgitation
- right ventricular hypertrophy
- comorbid atrial septal defect, ventricular septal defect & hypertrophic cardiomyopathy may be present [4]
Differential diagnosis:
- Down's syndrome
- pulmonary valve stenosis generally not present unless in association with tetralogy of Fallot [4]
Management:
- repair of severe pulmonary valvular stenosis regardless of symptoms [4,5]
Interactions
disease interactions
Related
Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia
Noonan-like syndrome (Noonan-like/multiple giant cell lesion syndrome)
Turner syndrome (ovarian agenesis)
General
congenital heart disease; congenital cyanotic heart disease
developmental disorder syndrome (multisystem disorder)
genetic disease of the heart
genetic syndrome (multisystem disorder)
Database Correlations
OMIM correlations
References
- Stedman's Medical Dictionary 26th ed, Williams &
Wilkins, Baltimore, 1995
- Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed)
Lippincott-Raven, Philadelphia, 1998, pg 47
- Harrison's Principles of Internal Medicine, 13th ed.
Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1038
- Medical Knowledge Self Assessment Program (MKSAP) 17, 18.
American College of Physicians, Philadelphia 2015, 2018
- Burch M, Sharland M, Shinebourne E et al
Cardiologic abnormalities in Noonan syndrome: phenotypic
diagnosis and echocardiographic assessment of 118 patients.
J Am Coll Cardiol. 1993 Oct;22(4):1189-92
PMID: 8409059
- Bhambhani V, Muenke M.
Noonan syndrome.
Am Fam Physician. 2014 Jan 1;89(1):37-43.
PMID: 24444506 Free PMC Article
- ARUP Consult: Noonan Spectrum Disorders Panel
https://arupconsult.com/ati/noonan-spectrum-disorders-panel