A case of Smith-Lemli-Opitz syndrome confirmed by molecular analysis: Review of mutation spectrum of the DHCR7 gene in Korea

Smith-Lemli-Opitz syndrome (SLOS) is a rare autosomal recessive disorder caused by 7-dehydrocholesterol reductase deficiency. The characteristic clinical features are syndactyly of the second and third toes, facial dysmorphism, multiple malformations, and intellectual disability. Few cases of SLOS have been reported in Korea. We observed a male patient with SLOS who presented with typical facial features, undescended testes, microcephaly, bilateral syndactyly of the second and third toes, and cardiac defects, including patent ductus arteriosus and atrial septal defect. Mutation analysis of the DHCR7 gene identified compound heterozygous mutations of c.907G>A (p.Gly303Arg) and c.1055G>A (p.Arg352Gln). In a review of the literature, c.1054C>T (p.Arg352Trp) was the most common mutation reported in Far East Asian countries. This report describes the clinical features, biochemical data, molecular characteristics, and clinical outcome of a Korean patient with SLOS.

A Novel DHCR7 Mutation in a Smith-Lemli-Opitz Syndrome Infant Presenting with Neonatal Cholestasis

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive malformation syndrome caused by a defect in cholesterol biosynthesis. The incidence is very low in Asians and only one case has been reported in Korea thus far. Recently, we found an infant with neonatal cholestasis. He had microcephaly, ambiguous genitalia, cleft palate, syndactyly of toes, patent ductus arteriosus and hypertrophic pyloric stenosis. The serum cholesterol was decreased and serum 7-dehydrocholesterol was markedly elevated. Genetic analysis of the DHCR7 gene identified a novel missense mutation (Pro227Ser) as well as a known mutation (Gly303Arg) previously identified in a Japanese patient with SLOS. Although rare in Korea, SLOS should be considered in the differential diagnosis of neonatal cholestasis, especially in patients with multiple congenital anomalies and low serum cholesterol levels.

A case of Smith-Lemli-Opitz syndrome diagnosed by identification of mutations in the 7-dehydrocholesterol reductase (DHCR7) gene / 소아과

Smith-Lemli-Opitz syndrome (SLOS) is a rare, autosomal recessive disease caused by an inborn error in cholesterol synthesis. Patients with this disease suffer from multiple malformations due to reduced activity of 7-dehydrocholesterol reductase (DHCR7), which increases 7-dehydrocholesterol (7DHC) and 8-dehydrocholesterol (8DHC) concentrations and decreases cholesterol concentration in body fluids and tissue. The SLOS phenotypic spectrum ranges from a mild disorder with behavioral and learning problems to a lethal disease characterized by multiple malformations. Here, we describe a newborn male with ambiguous genitalia who was diagnosed to have type II SLOS during the neonatal period. A clinical examination revealed low levels of unconjugated estriol in the maternal serum, and a variety of fetal ultrasound anomalies, including prenatal growth retardation. After birth, the infant was diagnosed to have congenital heart disease (Tetralogy of Fallot with severe pulmonary artery stenosis), cleft lip and palate, micrognathia, postaxial polydactyly, ambiguous genitalia, and cataracts. Clinical investigation revealed extremely low plasma cholesterol levels and the presence of mutation (homozygote of p.Arg352Gln) in the DHCR7 gene. The patient underwent palliative heart surgery (to widen the pulmonary artery) and received intravenous lipid supplementation. Cholesterol levels increased slightly, but not to normal values. The patient died from cardiopulmonary failure and sepsis 72 days after birth. This report provides the first description of a Korean patient with SLOS confirmed by verification of DHCR7 gene mutation and illustrates the need for early recognition and appropriate diagnosis of this disease.