Smith-Lemli-Opitz syndrome. 7-dehydrocholesterol-delta-7 reductase deficiency
Incidence
AR inheritance. Seen more often in males. It is one of the most common polymalformative syndromes. The incidence is 1:20,000. It is related to a cholesterol biosynthesis dysfunction.
Clinical Characteristics
It may manifest at birth with hypotonia and dysmorphic features. Characteristic facial features are usually evident at birth. They include ptosis, low set posteriorly rotated ears, antiverted broad nares. Micrognatia, hypospadia and other multiple congenital anomalies on limbs (syndactily of toes and polydactily) and viscera. Microcephaly, mental retardation, behavioral problems often serious. Failure to thrive, seizures in some patients, hypotonia, high forehead, cataracts, cleft palate, genital anomalies in males like chryptorchidea, hypospadia and ambigual genitalia, endocrine abnormalities, heart and kidney malformation, global developmental delay. Plasma cholesterol levels are very low with elevation of precursor 7-dehydrocholesterol (7-DHC). Gas chromatography (GC) analysis of sterols show that cholesterol levels are low and 7-DHC is high in plasma, RBCs and fibroblasts. When plasma cholesterol level is measured in plasma using enzymatic colorimetric analysis, the level is not decreased (due to lack of discrimination between cholesterol and 7-DHC). The mortality is high in the first year of life. There are brain abnormalities including microencephaly, hypoplastic frontal lobes, abnormal gyration and cerebellar hypoplasia. It may be a history of persistent vomiting. Some patients have simian creases. Has been reported marked improvement in neurological development and behavior when patients are placed in high cholesterol diet.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
Plasma cholesterol levels are very low with elevation of precursor 7-dehydrocholesterol (7-DHC). Gas chromatography (GC) analysis of sterols show that cholesterol levels are low and 7-DHC is high in plasma, RBCs and fibroblasts. When plasma cholesterol level is measured in plasma using enzymatic colorimetric analysis, the level is not decreased (due to lack of discrimination between cholesterol and 7-DHC).