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A syndrome characterized by the inability to make cholesterol. Affects the central nervous system (CNS) (white matter) and characterized by growth retardation, developmental delay, severe dysphagia, microcephaly, micrognathia, cleft palate, cataracts, ptosis, polysyndactyly and syndactyly of the second and third toes, and congenital heart defects (transposition of the great vessels is frequent). Congestive heart failure and liver failure are not uncommon.

RSH Syndrome; SLOS I Syndrome; 7-Dehydrocholesterol Reductase Deficiency.

1:20,000 to 1:60,000 live births in the United States among white people. Smith-Lemli-Opitz syndrome is uncommon in Hispanic population. Carrier frequency for Smith-Lemli-Opitz syndrome is approximately 1 in 30 in individuals of northern European descent, suggesting a disease incidence between 1:5000 and 1:18,000 in Europe. Internationally, Smith-Lemli-Opitz syndrome has been described in patients from the United States, Japan, South America, and Canada.

Results from a mutation in either the DHCR7 (7-dehydrocholesterol-delta7-reductase) gene on chromosome 11 or the SLOS gene on chromosome 7. Autosomal recessive inheritance.

The classic paradigm is an inborn error of metabolism, which includes the accumulation of a toxic precursor (7DHC) leading to the deficiency in production of an essential product (cholesterol). The absence in cholesterol can be implicated in the production of all the anomalies described. Cholesterol is required for normal development because of its involvement in cell and mitochondrial membranes, as well as steroid metabolism and myelination.

As a result of the defect in cholesterol metabolism, serum cholesterol levels are very low and levels of 7-dehydrocholesterol (a cholesterol precursor) are high in serum as well as any other tissue specimens. This biochemical finding associated with the clinical findings confirms the diagnosis of Smith-Lemli-Opitz syndrome. The mortality/morbidity is associated with stillbirths, or spontaneous abortion, or immediately after birth from multiorgan failure (during the first week of life). Causes of death include pneumonia, lethal congenital heart defect (most often transposition of the great vessels), congestive heart failure (not uncommon), and hepatic failure.

Prognosis is poor. Neuromuscular: initially hypotonia followed later by hypertonia; mental deficiency can be severe (IQ as low as 20); seizures and generalized nerve demyelination. Cardiovascular: malformations may be present in up to 44% of cases. The incidence of atrioventricular canal defects and anomalous pulmonary venous drainage is relatively high. Craniofacial: microcephaly, strabismus, epicanthic folds, elfin facies, ptosis, low-set ears, and micrognathia may be present. Genital tract: Developmental anomalies of the genital tract (particularly male) are common. Gastrointestinal/Nutrition: feeding difficulties and failure to thrive; Hirschsprung Disease may be more common.

Cardiac evaluation: echocardiogram to rule out congenital heart disease. Neurological assessment to evaluate degree of disability. Careful airway evaluation in view of micrognathia. The presence of frequent vomiting, feeding difficulties, electrolyte disturbances, and failure to thrive requires complete assessment.

The presence of muscular hypertonia raises the concern of malignant hyperthermia. Generalized muscle rigidity and hyperthermia have been reported following the use of halothane with and without succinylcholine. However, these episodes ...

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