CLINICAL AND MOLECULAR ANALYSIS OF XX SEX REVERSED PATIENTS

Purpose: The XX male syndrome presents with a spectrum of clinical app earances from phenotypic male individuals to true hermaphrodites. Prev ious reports established the sex determining region of the Y chromosom e (SRY) gene as the testis determining factor. However, a subset of XX sex reversed male individuals exists without a translocation of SRY d eoxyribonucleic acid (DNA) material to the X chromosome. In addition t o clinical or endocrinological criteria, Y DNA probe studies, and radi ological and surgical evaluation as indicated are necessary for an acc urate diagnosis. Materials and Methods: We evaluated 5 XX sex reversed patients (2 true hermaphrodites and 3 male individuals) by physical e xamination, pedigree analysis, endocrinological testing, molecular ana lysis of Y DNA, radiological studies and surgery (exploration and/or b iopsy). Results: All patients were SRY gene negative. Two patients wer e siblings. Complete endocrinological testing was negative in all case s. Two patients had a normal male phenotype. Radiological findings con firmed by cystoscopy or laparoscopy revealed a utricle, vesicoureteral reflux, and cervix and uterus in various patients. Gonadal biopsy sho wed ovotestes or ovary and testis in the 2 true hermaphrodites. The 3 XX male individuals had normal immature testes on biopsy. Conclusions: Categories of XX sex reversal include classic XX male individuals wit h normal phenotypes, nonclassic XX male individuals with sexual ambigu ity and XX true hermaphrodites. Simple translocation of the SRY gene t o the X chromosome does not always account for testicular differentiat ion and a male phenotype. The masculinization of our patients in the a bsence of SRY suggests an alteration of 1 or more downstream Y, X or a utosomal testis determining genes. We present another theory for male sex determination, including a downstream gene on the X chromosome in which expression is influenced by X inactivation. Y DNA genomic analys is, radiological studies and laparoscopic evaluation with gonadal biop sy as appropriate are recommended for complete assessment and treatmen t of these intersex patients.