CLINICAL AND ANATOMICAL SPECTRUM IN XX SEX REVERSED PATIENTS - RELATIONSHIP TO THE PRESENCE OF Y-SPECIFIC DNA-SEQUENCES

OBJECTIVE Testicular differentiation can occur in the absence of the Y chromosome giving XX sex-reversed males. Although Y chromosomal seque nces can be detected in the majority of male subjects with a 46,XX kar yotype, several studies have shown that approximately 10% of patients lack Y material including the SRY gene. The aim of this study was to s ee if the classification of XX sex-reversed individuals into three gro ups, Y-DNA-positive phenotypically normal XX males, Y-DNA-negative XX males with genital ambiguities and Y-DNA-negative true hermaphrodites can be applied to our cases. DESIGN Endocrinological and genetic studi es were conducted in 20 XX sex-reversed patients. PATIENTS Twenty pati ents with various phenotypes were studied. They were between 20 days a nd 35 years old. Ten presented ambiguous external genitalia (Prader's stages II to IV). After laparotomy or gonadal biopsy, the diagnosis wa s 46,XX true hermaphroditism in five, and XX male in 15. MEASUREMENTS Blood samples were obtained from all patients for hormonal and molecul ar studies. Basal levels of testosterone, oestradiol and pituitary gon adotrophins were measured by RIA. In addition, two stimulation tests w ere performed: gonadotrophin stimulation with GnRH and testicular stim ulation with hCG. Several Y-specific DNA sequences of the short arm of the Y chromosome were analysed by Southern blot and polymerase chain reaction methods. RESULTS In this study, three categories of XX sex-re versed individuals were observed: phenotypically normal males with or without gynaecomastia, males with genital ambiguities, and true hermap hrodites. Endocrinological data were similar in XX males and in true h ermaphrodites. Testosterone levels exhibited normal (n = 9) or decreas ed (n = 11) values. The hCG response was low. FSH and LH were elevated in 13 patients. Molecular analysis in ten patients showed varying amo unts of Y material including the Y boundary and SRY. Ten patients with various phenotypes lacked Y chromosomal DNA. There was no relation be tween Leydig cell function (as indicated by testosterone levels before or after hCG stimulation) and the presence of Y chromosome material. CONCLUSION Although the presence of Y-specific DNA generally results i n a more masculinized phenotype, exceptions do occur. In the Y-DNA-neg ative group, complete or incomplete masculinization in the absence of SRY suggests a mutation of one or more downstream non-Y, testis-determ ining genes.