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
Incidence estimated to be 1:25,000 live births.
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.
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.
Premedication may be desirable in view
of behavioral problems. Excessive skin folds on the arms may make
intravenous access difficult. The presence of congenital heart disease
dictates the anesthetic technique. If regional anesthesia is considered, the
extent of the peripheral neuropathy should be documented preoperatively.
Succinylcholine should be considered
relatively contraindicated in the presence of neonatal hypotonia.