45,X/46,XY mosaicism: Report of 27 cases

Objectives. There exist substantial differences between prenatally and post natally diagnosed cases of 45,X/46,XY mosaicism. Ninety percent of prenatal ly diagnosed cases show a normal male phenotype, whereas the postnatally di agnosed cases show a wide spectrum of phenotypes. This 10% risk of an abnor mal outcome in prenatally diagnosed cases requires further attention. The p urpose of the present study is to provide more information on the postnatal ly diagnosed 45,X/ 46,XY mosaicism cases. To date, only a few series have b een reported. An accurate diagnosis in these patients is essential not only to their follow-up, but also to providing appropriate genetic counselling and subsequent prenatal diagnosis to their parents. Methods. The clinical, cytogenetic, endocrinologic, histologic and molecula r biological findings of 27 patients with 45,X/46,XY mosaicism are analyzed . Results. The reported cases showed a wide spectrum of phenotypes as Turner syndrome, mixed gonadal dysgenesis (MGD), male pseudohermaphroditism (MPH) and apparently normal male. However, Ulrich-Turner stigmata were the most c ommon features found in this series. Patients with MGD or MPH presented wit h various degrees of sex reversal such as hypospadias and/or abnormal inter nal genitalia. No correlation between the proportion of the 45,X/46,XY cell lines in the blood or the fibroblasts and the phenotype was found. Mild me ntal retardation was present in 4 of the patients and 2 patients showed sig ns of autism. Conclusions. Two major points are emphasized in this series: 1) the presenc e in 7 histologically analyzed streak gonads of a homogeneous 45,X chromoso mal complement suggests that the invasion of the primitive genital ridge by a such a cell line may induce abnormal gonadal development; 2) 3 males, ap parently normal at birth, developed late onset abnormalities such as dysgen etic testes leading to infertility, Ulrich-Turner stigmata, dysmorphic feat ures, and mild mental retardation. These data indicate the importance of an accurate clinical and histologic evaluation of any patient presenting with 45,X/ 46,XY mosaicism.