Investigators at the Kennedy Krieger Institute and Johns Hopkins University, Baltimore; and the National Institutes of Health, Bethesda, MD, studied the relation between the size of the corpus callosum (CC), level of serum 7-dehydrocholesterol (7DHC), and severity of developmental delay in 36 subjects with Smith-Lemli-Opitz syndrome (SLOS), compared to 36 normal controls. The mean age was 3.9 yrs (range 0.2 – 12.5 yrs); 18 boys and 18 girls. Shorter CC length measured on one midsagittal image and smaller CC area correlated with a lower developmental quotient in gross motor and language domains, ranging from mild to severe, but not with fine motor or adaptive skills. Also, CC length and area negatively correlated with the 7DHC and 8DHC levels, and positively correlated with serum total cholesterol level. [1]

COMMENT. SLOS (or 7-dehydrocholesterol reductase deficiency) is an autosomal recessive metabolic and developmental congenital disorder, first described in 1964 [2]. The most commonly observed features include dysmorphic faces, microcephaly, 2-3 syndactyly of toes, polydactyly, growth retardation, intellectual disability, cleft palate, and hypospadias. Hypoplasia/agenesis of the corpus callosum is reported less frequently, as well as holoprosencephaly. Mutations in the DHCR7 gene are the cause, the enzyme responsible for production of cholesterol, an essential nutrient for embryonic development. Sequencing analysis of DHCR7 detects ∼96% of known mutations. [3]

MRI and 1H-MRS may prove effective in assessment of effects of cholesterol replacement therapy in patients with SLOS [4]. Of 18 patients with SLOS, abnormal CNS findings were noted in 5 patients, including callosal abnormalities in 4 (22%), Dandy-Walker variant in 1, arachnoid cyst in 1, and holoprosencephaly in 1 (6%). Clinical degree of disease severity was correlated with lipid:choline ratios.