A possible common origin of "Y-negative" human XX males and XX true hermaphrodites

Abstract

We have studied nine patients aged 1 month to 16 years with 46, XX karyotypes and testicular tissue. Some of these patients were followed through puberty. Phenotypically, two presented normal and seven abnormal external genitalia (AG). Among this latter group, four showed hypospadias and three true hermaphroditism (TH). The endocrine data were similar in all three groups: testosterone levels were within normal limits during puberty, decreasing in adulthood; gonadotrophin levels were above the control values at mid puberty. Histologies of the two sub groups of AG patients were identical up to 5 years of age and presented differences when compared with controls, regardless of the ovarian part of the ovotestis. However, in patients older than 8 years, germ cells disappeared and dysgenesis became obvious. In one patient, the ovarian zone of the gonad was detected only after complete serial sections of the removed gonad were examined. Southern blot analysis with Y-DNA probes displayed Y-specific material for the classic 46 XX males and a lack of such sequences for all patients with AG and TH. Based on these findings, we postulate that 46, XX males with AG and 46, XX TH may represent alternative manifestations of the same genetic defect. These data together with those concerning familial cases of 46, XX males with AG and 46, XX TH suggest an autosomally (or pseudoautosomally) determined mechanism.