Noonan Syndrome

At a glance

Part of group of RASopathies (mutations in the Ras/MAPK pathway) characterized by distinctive facial appearance, broad or webbed neck, low hairline in the back of the head, and short stature. Micrognathia, kyphosis and/or scoliosis, and cardiac defects (pulmonary valvular stenosis) are present. Other features include coagulation disorders, platelet deficiencies, mild mental retardation, and cryptorchidism in the first year of life.

Synonyms

Turner-like Syndrome; Pterygium Colli Syndrome.

History

Named after the American pediatric cardiologist Jacqueline Noonan, who described the association of valvular pulmonary stenosis and typical physical appearances in 1963.

Nature

Rare genetic disorder.

Incidence

1:1,000 to 2,500 live births.

Genetic inheritance

Autosomal dominant with variable phenotypic expression. At least 10 genes have been identified with more than 50% of patients having missense mutations of the PTPN11 gene on loci 12q22-qter and 12q24. Sporadic cases arise as a result of sporadic mutations. Normal karyotype.

Pathophysiology

Unknown. An abnormality of tissue migration in utero is suggested leading to lymphatic obstruction or dysfunction during development. This may be responsible for webbing of the neck and prominence of the trapezius, cryptorchidism, widely spaced nipples, low-set and posteriorly rotated ears, hypertelorism, and ptosis.

Diagnosis

Clinical features of ☞Ullrich-Turner Syndrome associated with pulmonary valve dysplasia and a normal karyotype. Genetic testing is available.

Clinical aspects

Noonan Syndrome is phenotypically similar to ☞Ullrich-Turner Syndrome. Neonate: Marked edema with excess nuchal skin. Infancy: Hypotonia, poor feeding.

Features of the Noonan phenotype are webbed neck with low posterior hairline, pterygium colli, flattened midface, cystic hygroma, pectus carinatum or excavatum, short stature (50%), high-arched palate, ptosis, hypertelorism, down-slanting palpebral fissures, dental malocclusion, micrognathia, strabismus, cryptorchidism, mental retardation (25%), kyphoscoliosis, and several skeletal abnormalities (spina bifida occulta, hemivertebra, narrow spinal canal, cubitus valgus). There is a risk of Arnold-Chiari Syndrome after childhood following a progressive enlargement of the cerebellum. Approximately 50% of patients have a cardiac problem, and Noonan Syndrome is the second most common syndromic cause after Trisomy 21. The most common cardiac anomalies are pulmonary stenosis, hypertrophic cardiomyopathy, atrial septal defect, tetralogy of Fallot, atrioventricular canal anomaly, and coarctation of the aorta. A third of patients with Noonan Syndrome will require cardiac surgery. Stature is short. Lymphedema may occur. Coagulopathy is frequent and most commonly caused by factor XI deficiency, although thrombocytopenia and deficiencies of factors XII and VIII are well described. Patients have a high risk of cancer for lymphoblastic or myeloblastic leukemias and rhabdomyosarcomas.

Precautions before anesthesia

Careful history to evaluate cardiac and respiratory function. Careful airway assessment for ...