A syndrome of multiple congenital anomalies characterized by midface hypoplasia, broad face, hearing loss (conductive and/or sensorineural), congenital heart defect, hypothyroidism, severe scoliosis, brachydactyly, and decreased pain sensitivity but peripheral neuropathy. Severe behavior problems (biting and head banging) and sleep disturbances.
Incidence estimated to be 1:25,000 live births, more than 100 patients described.
Anomaly caused by a chromosomal microdeletion (17p11.2) rather than a mutation. Many of the characteristics of this clinical entity may be a result of a disruption of the RAI1 gene.
Twelve genes have been identified within the deleted 17p11.2 region. The significance of the absence of these genes remains to be clarified, although single abnormalities of some of these genes give rise to distinct syndromes. In some series of patients, elevations of low-density lipoproteins are reported, suggesting that deletion of the sterol regulatory element binding protein (SREBF1) may play a role. Because this disorder is because of deletion in the area of chromosome 17, where a form of Charcot-Marie-Tooth maps, it has been suggested that the association of peripheral neuropathy and Smith-Magenis Syndrome should be considered a contiguous gene syndrome.
Diagnosis is based on the clinical phenotype and is confirmed by high-resolution cytogenetic studies.
All patients have a characteristic facial appearance (brachycephaly, midface hypoplasia, prominent forehead, broad nasal bridge) and a degree of mental retardation. Delayed speech development, hoarse voice, ocular abnormalities (strabismus, myopia, microcornea, iris anomalies, cataracts, optic nerve hypoplasia, and retinal detachment) and a peripheral neuropathy are common. Sleep disorders become more common during childhood. Decreased or absent rapid eye movement (REM) sleep has been demonstrated by polysomnography. The syndrome is classically associated with aggressive outbursts, attention-deficit, attention seeking behaviors, and self-harm. However, these patients are eager to please and respond well to adult attention. A history of infantile hypotonia is often present. Scoliosis is common (65% of patients). Less-common findings are congenital heart disease (37% of patients), major urogenital anomalies (35% of patients), hypothyroidism (29% of patients), immunoglobulin deficiencies (23% of patients), and cleft lip/palate (9% of patients). Behavioral and sleep disturbances may respond to treatment with carbamazepine or selective serotonin reuptake inhibitors.
Precautions before anesthesia
Obtain history of developmental milestones, abnormal behavior patterns, and current medical management. Examine for evidence of congenital heart disease, renal disease, and hypothyroidism. Assess severity and extent of the peripheral neuropathy. Carefully assess airway. Cardiovascular assessment, ECG, and echocardiography are essential if congenital heart disease is suspected. Consider formal assessment of lung function and chest radiograph in the presence of severe scoliosis. Laboratory investigations: consider assessing renal function and thyroid function.