1/6. cholesterol supplementation objectively reduces photosensitivity in the smith-lemli-opitz syndrome.Smith-Lemli-Opitz (SLO) affected children have multiple congenital physical and mental abnormalities; photosensitivity to ultraviolet A (UVA) has recently become a recognized feature. We present a patient with SLO and prominent photosensitivity in whom detailed phototesting has been performed at baseline and following 6 months of cholesterol supplementation. There was significant improvement in the symptoms of photosensitivity, confirmed objectively by phototesting and accompanied by partial correction of the biochemical abnormalities seen in SLO. This case report is the first to show that cholesterol supplementation in SLO can lead to an objective improvement in the associated photosensitivity.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
2/6. incidence of smith-lemli-opitz syndrome in ontario, canada.smith-lemli-opitz syndrome (OMIM 270400) (SLOS) is caused by inherited enzymatic deficiency of 3beta-hydroxysterol-Delta7-reductase (7-dehydrocholesterol-Delta7-reductase, DHCR7). SLOS is diagnosed clinically by the demonstration of elevated levels of 7-dehydrocholesterol (7DHC) in body fluids or tissues. SLOS is associated with mental retardation of variable degree and severe behavior abnormalities. The physical abnormalities range from minor facial anomalies to lethal malformations of the central nervous system, heart, kidneys, and other organs. The exact incidence of SLOS is not known. Although there exist estimates of the incidence of SLOS ranging from 1 in 20,000 to 1 in 60,000, no prospective studies of the incidence of SLOS, based on the clinical data and biochemical diagnosis of SLOS, have been performed. Five unrelated cases of SLOS were diagnosed in ontario during a 12-month period. The diagnoses were made based on the demonstration of elevated 7DHC in plasma or amniotic fluid. The birth rate for ontario for that period was 132,000 births. The incidence of SLOS in ontario was at least 1 in 26,500 pregnancies in 1999-2000. Given that 86% of the population of ontario is of European origin, the incidence of SLOS in the ontario population of European origin was at least 1 in 22,700. As infants with mild forms of SLOS born during this period may remain undiagnosed, these numbers likely are underestimates. This observation has implications for prenatal and newborn screening for this potentially treatable inherited disorder.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
3/6. Recognition of smith-lemli-opitz syndrome (RSH) in the fetus: utility of ultrasonography and biochemical analysis in pregnancies with low maternal serum estriol.smith-lemli-opitz syndrome (SLOS), or RSH, is an autosomal recessive disorder caused by mutations of the gene encoding 7-dehydrocholesterol reductase (DHCR7). The utility of maternal serum screens and ultrasound as prenatal screening methods for SLOS is presently undetermined. We report the clinical, cytogenetic, biochemical, and molecular findings of a stillborn with SLOS. The diagnosis was made postnatally on the basis of physical findings and confirmed by biochemical and dna analyses of fetal tissue. Although abnormalities were detected by maternal serum triple screen and prenatal ultrasonography, a diagnosis of SLOS was not suspected before delivery. This study demonstrates that patients with SLOS may escape prenatal diagnosis despite the presence of multiple anomalies and abnormal maternal serum screen results, and lends support for consideration of prenatal biochemical testing for SLOS in pregnancies with these findings. As SLOS is a severe autosomal recessive disorder with a recurrence risk of 25%, ultrasonographic, cytogenetic, and biochemical analyses in the second trimester should be considered if abnormal maternal serum screening results, specifically low levels of unconjugated estriol, are detected.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
4/6. smith-lemli-opitz syndrome: thirty-year follow-up of "S" of "RSH" syndrome.We have reassessed patient "S," one of the first 3 individuals recognized to have Smith-Lemli-Opitz (or RSH) syndrome, at age 34 years, and we describe his physical, developmental, and behavioral manifestations. This reassessment provides formal evidence that this individual has the cholesterol biosynthetic defect which is thought to be the cause of smith-lemli-opitz syndrome. Dietary manipulation appears to have had a beneficial effect on the patient's behavior and suggests that even in adults with this condition, dietary cholesterol supplementation may be indicated.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
5/6. Variant RSH/smith-lemli-opitz syndrome with atypical sterol metabolism.The RSH/smith-lemli-opitz syndrome (RSH/SLOS) is an autosomal recessive malformation syndrome comprising microcephaly, developmental and growth retardation, characteristic facial anomalies, midline cleft palate, and genital and limb anomalies. Recently, biochemical evidence of an inborn error of cholesterol biosynthesis at the level of 7-dehydrocholesterol (7DHC) reductase was reported in children and adults with RSH/SLOS. We report on two sibs with a variant form of RSH/SLOS whose sterol metabolism in cultured lymphoblasts is abnormal but differs from that of patients with classical RSH/SLOS. The children have relatively mild physical and developmental abnormalities, but a phenotype still consistent with the diagnosis of RSH/SLOS. Their plasma cholesterol levels are only mildly depressed, and they have less markedly increased plasma levels of 7DHC than most patients with classical RSH/SLOS. Cultured lymphoblasts from our patients accumulated 7DHC to the same degree as classical RSH/SLOS lymphoblast when grown with cholesterol-depleted fetal calf serum. However, unlike other RSH/SLOS cells, the increase in cellular 7DHC levels was not suppressed when the cells were grown in the presence of cholesterol from untreated fetal calf serum. The parents' sterol metabolism was also strikingly abnormal in that the levels of 7DHC in their lymphoblasts were markedly elevated compared with those of lymphoblasts from other RSH/SLOS parents. Our findings suggest that these mildly affected RSH/SLOS sibs may have a genetic disorder of sterol metabolism that is related to but biochemically different from classical RSH/SLOS, possibly one affecting intracellular transport of sterols.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
6/6. smith-lemli-opitz syndrome: phenotypic extreme with minimal clinical findings.smith-lemli-opitz syndrome (SLO) is caused by inherited enzymatic deficiency of 7-dehydrocholesterol-delta7-reductase and resultant cholesterol deficiency. It comprises a characteristic combination of facial features, malformations, and mental retardation. We report on three related patients (two brothers and their first cousin) with mental retardation and minimal physical signs in whom the diagnosis of SLO was delayed for a number of years. The presence of a third-degree relative in the absence of consanguinity in this family supports the proposed high population carrier frequency. Our report suggests that cases of mild SLO remain undiagnosed and untreated, and that awareness of this common cause of mental retardation is low.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |