Circonstances cliniques du diagnostic du syndrome de Smith-Lemli-Opitz et tentatives de corrélation phénotype-génotype : à propos de 45 cas When should Smith-Lemli-Opitz syndrome be considered? A serie of 45 cases

Introduction. – SLO (Smith-Lemli-Opitz) syndrome is an autosomal recessive multiple congenital malformations syndrome, including mental retardation, failure to thrive, craniofacial abnormalities, incomplete development of male genitalia, limb anomalies and various interna l organ abnormalities. This syndrome is caused by a deficiency of cholesterol biosynthesis at the distal step of 7–dehydrocholesterol reductase (7DHCR). Patients and methods. – We have reviewed 45 cases of SLO syndrome and showed the large clinical spectrum of this syndrome. Results. – The prenatal diagnosis should be considered when dealing with antenatal growth retardation and visceral malformations. At birth, a normal weight does not systematically exclude the diagnosis. Diagnosis was more difficult for older children especially for girls and should be suspected on the association of mental retardation, autism, short stature and microcephaly. We found a correlation between low plasmatic cholesterol measurement and clinical severity. Phenotype-genotype correlation was difficult to establish. However, homozygosity for IVS8-1G>C splice site mutation was associated with severe phenotype.