A patient with Smith–Lemli–Opitz syndrome: novel mutation of the DHCR7 gene and effects of therapy with simvastatin and cholesterol supplement

• Published in: European journal of pediatrics Vol. 169; no. 1; pp. 121 - 123
• Main Authors: Szabó, Gabriella P., Oláh, Anna V., Kozak, Libor, Balogh, Erzsébet, Nagy, Andrea, Blahakova, Ivona, Oláh, Éva
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 2010; Springer Nature B.V
• Subjects: Child; Cholesterol - blood; Cholesterol - deficiency; Cholesterol, Dietary - administration & dosage; DNA - genetics; DNA Mutational Analysis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Male; Medicine; Medicine & Public Health; Mutation; Oxidoreductases Acting on CH-CH Group Donors - blood; Oxidoreductases Acting on CH-CH Group Donors - genetics; Pediatrics; Short Report; Simvastatin - administration & dosage; Smith-Lemli-Opitz Syndrome - blood; Smith-Lemli-Opitz Syndrome - drug therapy; Smith-Lemli-Opitz Syndrome - genetics; Smith–Lemli–Opitz syndrome; Cholesterol substitution; p.G366V; Simvastatin; Novel mutation
• ISSN: 0340-6199; 1432-1076
• DOI: 10.1007/s00431-009-0987-z

Background The Smith–Lemli–Opitz (SLO) syndrome is a multiple congenital anomaly with mental retardation due to a decreased or lack of activity of 7-dehydrocholesterol reductase as a consequence of mutations of the DHCR7 gene. This paper describes a special patient with SLO syndrome. Laboratory examination showed low cholesterol (2.77 mmol/L) and increased 7-dehydrocholesterol level (102 mg/L). Molecular genetic analysis revealed a compound heterozygosity c.964-1G>C/p.G366V (c.G1370T) of the proband. The p.G366V is a novel mutation of the DHCR7 gene with guanine by thymine nucleotide exchange resulting in glycin by valin amino acid exchange in the dehydrocholesterol reductase enzyme. Simvastatin (0.2 mg/kg/day) and cholesterol replacement therapy (150–250 mg/kg/day) led to significant improvement in the patient's laboratory findings (7-dehydrocholesterol, cholesterol) as well as in his behavior and gross motor function. Conclusion Our patient demonstrates that the c.964-1G>C/p.G366V (c.G1370T) genotype of combined heterozygosity is associated with a typical form of SLO syndrome along with moderately altered laboratory findings and a favorable biochemical response to cholesterol and simvastatin treatment.