Conditions · Pediatrics and neonatology
Noonan syndrome !
A genetic disorder with short stature, a webbed neck, typical facial features and heart disease, most often a narrowed pulmonary valve.
Updated 2026-11-01
Structures involved
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- Pulmonary anterior cusp
- Pulmonary right cusp
- Pulmonary left cusp
- Pulmonary trunk
- Interventricular septum
- Interatrial septum
- Thoracic duct
- Testes
Why it happens
What it is
An autosomal dominant RASopathy caused by variants in genes of the RAS/MAPK signaling pathway, most often PTPN11. It features short stature, distinctive facial features, a webbed neck and congenital heart disease, typically pulmonary valve stenosis or hypertrophic cardiomyopathy, with usually normal intelligence.
Who gets it
One of the most common genetic syndromes with heart disease, about 1 in 1,000 to 2,500 people; it affects both sexes equally.
Causes
- Gain-of-function variants in RAS/MAPK pathway genes: PTPN11 (about half), SOS1, RAF1, RIT1 and others
- Autosomal dominant inheritance; many cases are new variants, others inherited from a mildly affected parent
Risk factors
- Parent with Noonan syndrome (50% transmission risk)
Pathophysiology
Overactive RAS/MAPK signaling alters cell growth and differentiation in many tissues. In the heart it causes thickened, dysplastic pulmonary valve leaflets and, especially with RAF1 variants, hypertrophic cardiomyopathy. Abnormal development of lymphatic vessels causes nuchal edema in the fetus (later a webbed neck), lymphedema and chylous effusions. Clotting factor deficiencies and platelet dysfunction cause bleeding, and growth and pubertal delays are common.
Symptoms and signs
- Facial features: hypertelorism, down-slanting palpebral fissures, ptosis, low-set posteriorly rotated ears, triangular face
- Short or webbed neck with a low posterior hairline
- Short stature
- Chest deformity (pectus carinatum above, pectus excavatum below), widely spaced nipples
- Heart murmur from pulmonary valve stenosis; signs of hypertrophic cardiomyopathy
- Easy bruising and bleeding
- Cryptorchidism and delayed puberty in boys; lymphedema in infancy; mild learning difficulties in some
Diagnosis
- Clinical
- Clinical diagnosis based on facial features, short stature, heart disease, chest deformity, family history and other features; may be suspected prenatally from increased nuchal translucency or cystic hygroma with a normal karyotype.
- Tests
- Molecular testing with a RASopathy gene panel confirms most cases. ECG, which often shows a superior (left) axis deviation. Coagulation studies (clotting factors and platelet function) before surgery; complete blood count; growth assessment.
- Imaging
- Echocardiogram for pulmonary valve stenosis, septal defects and hypertrophic cardiomyopathy; renal ultrasound and spine assessment as needed.
Differential diagnosis
- Turner syndrome (girls; confirmed by karyotype)
- Other RASopathies: Costello, cardiofaciocutaneous syndrome, neurofibromatosis type 1, Noonan syndrome with multiple lentigines
- Williams syndrome
- Fetal alcohol spectrum disorder
Goal of treatment
Treat the heart lesion, support growth and development, prevent bleeding complications and screen for associated problems throughout life.
Treatment
- Surgical
- Balloon valvuloplasty (or surgical valvotomy for dysplastic valves) for significant pulmonary stenosis; surgery for septal defects or obstructive cardiomyopathy when needed; orchiopexy for undescended testes.
- Medical
- Growth hormone therapy in selected children with short stature; medical treatment of hypertrophic cardiomyopathy; bleeding precautions and factor or hemostatic support before procedures.
- Rehabilitation
- Early intervention, speech and physical therapy and school support when there are developmental or learning difficulties.
- Follow-up
- Regular cardiology follow-up, growth and puberty monitoring, blood counts, vision and hearing checks; genetic counseling.
Complications
- Heart failure or arrhythmias from cardiomyopathy
- Bleeding complications
- Lymphedema and chylous effusions
- Infertility in males with cryptorchidism
- Juvenile myelomonocytic leukemia and other cancers (increased risk)
Prognosis
Most people live into adulthood with good quality of life; prognosis depends mainly on the heart disease, being worse in infants with severe hypertrophic cardiomyopathy.
Test yourself
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What is the most common heart lesion in Noonan syndrome?
Pulmonary valve stenosis, often with a dysplastic valve.
Which gene is most often affected?
PTPN11, in the RAS/MAPK pathway (about half of cases).
How does Noonan syndrome differ from Turner syndrome?
Noonan is autosomal dominant with a normal karyotype, affects both sexes and causes right-sided heart lesions; Turner (45,X) affects girls and causes left-sided lesions such as coarctation and bicuspid aortic valve.
Which test should be done before surgery in a child with Noonan syndrome?
Coagulation studies, because of clotting factor deficiencies and platelet dysfunction.
Related conditions
- Turner syndrome
- Pulmonary valve stenosis
- Hypertrophic cardiomyopathy
- Atrial septal defect
- Cryptorchidism (undescended testis)
- Von Willebrand disease
- Neurofibromatosis (types 1 and 2)
- Acute leukaemia (AML and ALL)
- Lymphoedema
- Williams syndrome
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Noonan syndrome (MedlinePlus Genetics (U.S. National Library of Medicine), 2024).
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