A neonate with Smith-Lemli-Opitz syndrome caused by DHCR7 gene compound heterozygous variations / 中华围产医学杂志

This article reported a male neonate with Smith-Lemli-Opitz syndrome (SLOS) caused by DHCR7 gene compound heterozygous variations. The patient presented with multiple malformations and feeding difficulties after birth and was transferred to the First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) from a local hospital eight days later. Physical examination found general scleredema, scalp defects, short penis, urinary tract malformation, bilateral syndactyly of the second and third toes, and low serum cholesterol. Whole-exome and Sanger sequencing indicated a compound heterozygous mutation in the DHCR7 gene, c.852C>A(p.F284L), and a de novo mutation of c.820_825del(p.N274_V275del). SLOS is rare in the Asian populations and prone to missed diagnosis and misdiagnosis with difficulty in clinical management. The possibility of SLOS should be considered for newborns with multiple malformations and low serum cholesterol.

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.

Smith-Lemli-Opitz-syndrome.

Smith-Lemli-Opitz syndrome is an autosomal recessively inherited disorder. A severe defect in cholesterol biosynthesis has been identified leading to abnormally low plasma cholesterol levels and elevated levels of the cholesterol precursor 7-dehydrocholesterol, the result of deficiency of 7-dehydrocholesterol reductase. We describe one such child with Smith-Lemli-Opitz syndrome. This child had clinical features similar to Smith-Lemli-Opitz syndrome like facial dysmorphism and cardiac and renal anomalies with failure to thrive.

Rehabilitación oral de un paciente pediátrico con síndrome de Smith-Lemli-Opitz bajo anestesia general ambulatoria / Oral rehabilitation of a pediatric patient with smith-lemli-opitz syndrome under outpatient general anesthesia

El síndrome de Smith-Lemli-Opitz es una rara enfermedad hereditaria de transmisión autosómica recesiva. Se caracteriza por presenta hipocolesterolemia como consecuenciade una mutación del gen 7-deshidrocolesterol reductasa (7DHCR), lo que produce retrasomental, retardo en el crecimiento, microcefalia, micrognatismo y otras anomalías neurológicas sistémicas y físicas. Se presenta el caso de un paciente de tres años y nueve mesesafectado por este síndrome, quien acudió a la clínica de odontología pediátrica de la Facultad de Odontología de la Universidad Autónoma de Baja California, Tijuana, donde se inició historia médica y dental. Debido a su corta edad, la presencia de múltiples lesiones cariosas, conducta incontrolable, retraso mental y compromiso sistémico, se decidió realizar larehabilitación oral del paciente bajo anestesia general, la cual se describe detalladamente...

Smith-Lemli-Opitz syndrome is a rare autosomal recessive hereditary disease. It is caused by a mutation in the 7-dehydrocholesterol reductase (DHCR7) gene producing hypocholesterolemia,and consequence mental retardation, delayed growth, microcephaly, micrognathia and other systemic neurological and physical features. A case of a three-year-ninemonth-old patient affected by this syndrome who attended the Pediatric Dental Clinic of the Universidad Autónoma de Baja California Dental School at Tijuana is presented. Afterdoing medical and dental records and because of his young age, multiple dental cavities, uncontrollable behavior, mental retardation and medical status, oral rehabilitation under general anesthesia was performed. The anesthesia procedure is detailed...

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.

A Case of Trisomy 9 Mosaicism Mimicking Smith-Lemli-Opitz Syndrome

Trisomy 9 mosaicism is a disease characterized not only by intrauterine growth retardation and mental retardation but also congenital heart defects, musculoskeletal, genitourinary and CNS anomalies, as well as craniofacial anomalies such as microcephaly, micrognathia, narrowed temples, prominent occiput, broad-based nose with bulbous tip, low set ears, deeply set eyes, short palpebral fissure and small mouth. This syndrome was first reported back in 1973 by Haslam and others, and has hardly ever been reported since. In Korea, a complete form of trisomy 9 syndrome was first reported in 1998 by Chun and others, but trisomy 9 mosaicism has not been reported yet. We recently experienced a case with a patient who was most likely suspected as diet therapy requiring Smith-Lemli-Opitz Syndrome(SLO), since the patient had unilateral ptosis, hypospadias, micrognathia, simian crease, and low set ears, which are the characteristics not yet reported as trisomy 9 mosaicism, but most similar to Smith-Lemli-Opitz syndrome. Also, the patient did not show the typical characteristics of trisomy 9 mosaicism such as broad nose or enophthalmosis. However, further evaluation was taken in order to make the correct diagnosis, and the serum cholesterol level of the patient was shown to be normal, which implied normal cholesterol metabolism, but the chromosomal studies of the patient confirmed the karyotype of 47,XY,+9/46,XY, which proved that the patient has trisomy 9 mosaicism.