Noonan Syndrome

Rare genetic disorder present at birth. 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.

Turner-like Syndrome.

Rare genetic disorder. Noonan syndrome is phenotypically similar to Turner syndrome; however, the karyotype in Noonan syndrome is normal.

1:1000-2500 live births.

Autosomal dominant with variable phenotypic expression. Genes have been identified on loci 12q22-qter and 12q24. Sporadic cases arise as a result of sporadic mutations.

Unknown. An abnormality of tissue migration in utero is suggested, and the presence of cystic hygromas and lymphedema is cited as evidence supporting this hypothesis.

Clinical features of Turner syndrome associated with pulmonary valve dysplasia and a normal karyotype.

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). Approximately 50% of patients have a cardiac problem. The most common cardiac anomalies are pulmonary stenosis, hypertrophic cardiomyopathy, atrial septal defect, tetralogy of Fallot, atrioventricular canal anomaly, and coarctation of the aorta. 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.

Careful history to evaluate cardiac and respiratory function. Careful airway assessment for potentially difficult laryngoscopy and tracheal intubation. Electroencephalogram, and echocardiography to assess cardiac function/anatomy must be obtained. Cervical spine radiography to exclude atlantoaxial instability and any other anomaly is highly recommended. Lumbosacral spine radiograph if a neuraxial block is foreseen must be done to exclude vertebral anomalies. Consider chest radiograph and pulmonary function tests in presence of severe kyphoscoliosis. Laboratory investigation for coagulopathy is mandatory if regional techniques are under consideration. Continue perioperative medications, especially if taking beta-blocker for hypertrophic obstructive cardiomyopathy.

Short or webbed neck, micrognathia, and dental malocclusion may make direct laryngoscopy and tracheal intubation difficult. Anesthetic management according to cardiac malformation. Regional techniques have been used but require careful assessment of cardiac function, coagulation, and vertebral anatomy.

Isoflurane may cause undesirable tachycardia. Esmolol may be useful in the presence of hypertrophic obstructive cardiomyopathy.

Watson Syndrome: Rare disease combining pulmonary valvular stenosis with café-au-lait spots, dull intelligence, and short stature. Other features include macrocephaly and iris Lisch nodules in most cases, a condition that overlaps those of neurofibromatosis and the Noonan syndrome.

LEOPARD Syndrome: Complex congenital dysmorphogenetic disorder associating mainly skin lesions (lentigines, multiple), electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and deafness (sensorineural).

Costello Syndrome: Syndrome characterized by postnatal growth deficiency, coarse facies, redundant skin on the neck, acanthosis nigricans, developmental delay, and papillomata.

Reynolds Neri Hermann Syndrome: Characterized by unusually sparse, brittle, curly hair, macrocephaly, prominent forehead with abnormal narrowing of the sides of the forehead (temporal constriction), mental retardation, failure to thrive, congenital heart defect, short stature, and ectodermal abnormalities.

Noonan-like Multiple Giant Cell Lesion Syndrome: Rare disorder characterized by giant cells lesions within bone and soft tissue of the jaw; the presence of “freckle-like” spots on the skin (lentigines), pulmonary valve stenosis, and dwarfism. Other features include ocular hypertelorism, abnormally prominent, improperly positioned ears, pterygium colli, and cubitus valgus. Occurs sporadically as a consequence of new genetic mutations.

Quattrin McPherson Syndrome (Neurofibromatosis Noonan Syndrome): Same clinical features as reported for Noonan syndrome, except with characteristic facial appearance (macrosomia), developmental delay, and dysmorphism in presence of neurofibromatosis. Rare. First reported in 1987.