Disease Directory Noonan Syndrome
Connective Tissue

Noonan Syndrome

Also known as: male Turner syndrome, NS, PTPN11/RAS-MAPK pathway

Prevalence

1 in 1,000–2,500

Onset

Congenital

Type

Genetic — autosomal dominant (50% de novo)

Gene

PTPN11, SOS1, RAF1, RIT1 (multiple)

About Noonan Syndrome

Noonan syndrome is one of the most common autosomal dominant conditions, caused by gain-of-function mutations in genes encoding components of the RAS-MAPK signalling pathway, with PTPN11 (encoding SHP-2 phosphatase) accounting for approximately 50% of cases. The phenotype includes characteristic facial dysmorphology, congenital heart defects (particularly pulmonary valve stenosis and hypertrophic cardiomyopathy), short stature with growth hormone axis dysregulation, and variable neurodevelopmental involvement. Individuals with RAF1 and RIT1 mutations carry a higher risk of hypertrophic cardiomyopathy, while PTPN11 mutations are associated with an increased risk of juvenile myelomonocytic leukaemia.

Common Clinical Features

Short stature with growth hormone insufficiency or resistance Pulmonary valve stenosis or other congenital heart defects Hypertrophic cardiomyopathy (particularly with RAF1/RIT1 mutations) Characteristic facies: hypertelorism, ptosis, downslanting palpebral fissures, low-set ears Webbed neck and low posterior hairline Bleeding diathesis from coagulation factor deficiencies or platelet dysfunction Cryptorchidism in males and variable neurodevelopmental delay

Clinical Trial Eligibility Tips

What to know before applying to Noonan Syndrome trials.

Current echocardiogram (within 12 months) documenting cardiac anatomy, valvular gradients, and LV wall thickness is a universal enrolment requirement — ensure this is performed by a paediatric or congenital cardiologist.

Specific gene identification within the RAS-MAPK pathway is required by most trials, as therapies targeting MEK or SHP-2 have differential efficacy across genotypes.

Growth records plotted on Noonan syndrome-specific growth charts, current height SDS, and prior or current growth hormone therapy history must be documented for trials with height or growth velocity endpoints.

Patient Resources

Patient Organization

The Noonan Syndrome Association

Visit website ↗

Natural History Registry

RASopathies Network Registry

Join registry ↗

Orphanet

European reference resource for rare diseases (ORPHA:648)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

Search NORD ↗

Find recruiting Noonan Syndrome trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for Noonan Syndrome. Updated daily.

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