Phenotypic spectrum of fetal Smith-Lemli-Opitz syndrome.

International audienceThe Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple congenital malformation syndrome caused by dehydrocholesterol reductase deficiency. The diagnosis is confirmed by high 7- and secondarily 8-dehydrocholesterol levels in plasma and tissues and/or by detection of biallelic mutations in the DHCR7 gene. The phenotypic spectrum of SLOS is broad, ranging from a mild phenotype combining subtle physical anomalies with behavioral and learning problems, to a perinatally lethal multiple malformations syndrome. The fetal phenotype of SLOS has been poorly described in the literature. We report a series of 10 fetuses with molecularly proven SLOS. Even in young fetuses, the facial dysmorphism appears characteristic. Genital abnormalities are rare in 46,XX subjects. Gonadal differentiation appears histologically normal and in agreement with the chromosomal sex, contrary to what has been previously stated. We observed some previously unreported anomalies: ulnar hypoplasia, vertebral segmentation anomalies, congenital pulmonary adenomatoid malformation, fused lungs, gastroschisis, holomyelia and hypothalamic hamartoma. This latter malformation proves that SLOS phenotypically overlaps with Pallister-Hall syndrome which remains clinically a major differential diagnosis of SLOS

Paganisme, syncrétisme et culture religieuse populaire au haut Moyen Âge. Réflexions de méthode

Paganism Syncretism and Popular Religious Culture in the Early Middle Ages : Observations on Method. The author describes few divergences between, on the one hand, research on religious culture in the history of mentalities, and, on the other hand, post-war German research on paganism and syncretism. He raises the question of whether the two lines of research can be integrated. Taking account of the fact that the stereotypicity of early medieval sources has given rise to serious doubts regarding the authenticity of their descriptions of paganism and syncretism the author suggests number of criteria that could be used to prove or argue that part of the material contained in these sources can reasonably be held to be authentic. Finally he considers the possibility of comparative investigation of the subject. By way of example he compares certain aspects of the christianization of occidental Europe in the Early Middle Ages and that of Peru in the 16th century.Künzel Rudi, Chevy Françoise. Paganisme, syncrétisme et culture religieuse populaire au haut Moyen Âge. Réflexions de méthode. In: Annales. Économies, Sociétés, Civilisations. 47ᵉ année, N. 4-5, 1992. pp. 1055-1069

Molecular mechanisms underlying limb anomalies associated with cholesterol deficiency during gestation: implications of Hedgehog signaling.

Human disorders caused by inborn errors of cholesterol biosynthesis are characterized by dysmorphogenesis of multiple organs. This includes limb malformations that are observed at high frequency in some disorders, such as the Smith-Lemli-Opitz syndrome, indicating a pivotal role of cholesterol in limb morphogenesis. Recently, it has been demonstrated that cholesterol can modulate the activity of the Hedgehog proteins, that act as morphogens to regulate the precise patterning of many embryonic structures, among which the developing limbs. To provide insight in the functions of cholesterol during limb development and in the potential role of Hedgehog signaling in the genesis of limb defects, we developed an in vivo rat model of cholesterol deficiency. We show here that treatment with Triparanol, a distal inhibitor of cholesterol biosynthesis, induced patterning defects of the autopod at high frequency, including pre-axial syndactyly and post-axial polydactyly, thus reproducing limb anomalies frequently observed in humans. Using in situ hybridization, we show that these malformations originate from a modification of Sonic Hedgehog signaling in the limb bud at 13 days post-coitum, leading to a deficiency of the anterior part of the limb. This deficiency results in an imbalance of Indian Hedgehog expression in the forming cartilage, ultimately leading to reduced interdigital apoptosis and syndactyly. Our study thus unravels the molecular mechanisms underlying the genesis of limb defects associated with cholesterol deficiency in rodents, and most probably in humans