Female external genitalia and müllerian duct derivatives in a 46,XY infant with the Smith‐Lemli‐Opitz syndrome

Abstract

We report on a 46,XY newborn infant with Smith-Lemli-Opitz (SLO) syndrome with female external genitalia, intraabdominal testes with epididymides and deferent ducts and a normally shaped uterus and vagina. Polydactyly, cleft palate, and several internal organ malformations were also present, and the patient died shortly after birth. Data on six reported male infants with SLO syndrome and female external genitalia suggest a correlation between degree of genital involvement and overall degree of severity. Scoring systems to quantify overall degree of severity (SLO score) and degree of genital involvement in males (genital score) were devised and applied to 122 reported cases from the literature. Statistical analyses showed a unimodal distribution of the SLO severity scores, and positive correlations between the SLO score and the genital score in males, the presence of polydactyly, and the presence of cleft palate. In 19 multiplex families the affected sibs were generally similar in their SLO scores. The above analyses suggest that the wide phenotypic variability in the SLO syndrome is determined by variable expressivity of the same entity as opposed to genetic heterogeneity. The observed phenotypic correlations naturally determine that males with complete feminization are among the more severe patients and tend to have polydactyly and cleft palate.

Residual cholesterol synthesis and simvastatin induction of cholesterol synthesis in Smith–Lemli–Opitz syndrome fibroblasts

“…Some of this variation may be due to limitations of the severity score. The severity score, initially developed by Bialer et al [48] to separate type I and type II SLOS, was subsequently modified by Kelly and Hennekam [11] to evaluate severity of physical malformations. With continued expansion of the SLOS phenotypic spectrum, limitations of this scoring system to differentiate among cases have become apparent.…”

Malformation syndromes caused by disorders of cholesterol synthesis

“…Structural brain malformations including holoprosencephaly and abnormalities of the corpus callosum ( 35,(42)(43)(44) can be observed in more severely affected subjects. Phenotypic severity, based on the degree and number of physical malformations, can be quantifi ed using a severity score initially developed by Bialer et al ( 45 ) and subsequently modifi ed by Kelley et al ( 20 ).…”

Assays of plasma dehydrocholesteryl esters and oxysterols from Smith-Lemli-Opitz syndrome patients

“…Because SLOS shows a wide clinical variation, the clinical degree of severity was determined by a scoring system that takes account of the anatomical abnormalities, fi rst suggested by Bialer et al ( 22 ) and then modifi ed by Kelley and Hennekam ( 4 ). The severity scores in our patients ranged from 9 to 41.…”