We report on two sets of monozygotic twins (MZTs) discordant for phenotypic sex ascertained at birth when the female twin was noted to have signs of the Ullrich-Turner syndrome. Cytogenetic investigations on the female of the first pair showed 45,X/46,XY mosaicism in lymphocytes but fibroblasts grown from two skin biopsies at separate sites and from gonadal tissue showed only 45,X cells. The male showed mosaicism in both blood lymphocytes and skin fibroblasts. In the second family, both twins also showed mosaicism in lymphocytes. The female had a 45,X karyotype in fibroblasts from skin and gonadal tissue, but in contrast to the first family, the male twin had a normal male karyotype in fibroblasts from skin biopsy and from connective tissue adjacent to the vas deferens. Discordant phenotypic sex in monozygotic twins is rare. As in our cases, the nine previously reported sets of MZTs all had mosaicism for sex chromosome abnormalities. A mitotic error leading to the loss of a Y chromosome prior to, accompanying, or following the twinning process would account for the reported combinations of karyotypes.

Amniocentesis was performed at 17.3 weeks in a pregnancy with severe intrauterine growth retardation. Cytogenetic studies on amniocytes were normal, 46,XX, and the pregnancy was continued. The diagnosis of Smith-Lemli-Opitz syndrome was suspected in the neonatal period and confirmed by the presence of 7-dehydrocholesterol (7-DHC) in the plasma (0.4 mmol/l, normal = not detectable) associated with a low total cholesterol concentration (0.4 mmol/l, normal = 2.56 +/- 0.23). Retrospective analysis of the amniotic fluid sample revealed an elevated level of 7-DHC (0.022 mmol/l; normal = undetectable). Therefore measurement of 7-DHC levels in amniotic fluid during the second trimester of pregnancy is useful for the prenatal diagnosis of Smith-Lemli-Opitz syndrome in families at risk and should be considered in cases of severe growth retardation of unknown aetiology for which amniotic fluid is available and in which a normal chromosomal pattern in amniocytes is present.