Clinical characteristics and diagnosis of Smith-Lemli-Opitz syndrome and tentative phenotype-genotype correlation: report of 45 cases]

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 internal organ abnormalities. This syndrome is caused by a deficiency of cholesterol biosynthesis at the distal step of 7-dehydrocholesterol reductase (7DHCR).We have reviewed 45 cases of SLO syndrome and showed the large clinical spectrum of this syndrome.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.Better understanding of the 7DHCR gene regulation factors and of the compensatory mechanism of foeto-maternal cholesterol transfer are necessary to explain the wide clinical spectrum of the SLO syndrome.