46,XX Male Patients—Clinical and Genetic Findings in Six Patients

Abstract

We describe the clinical and molecular genetic findings of six 46,XX male patients evaluated at our institution. 46,XX male syndrome is described elsewhere in the literature as a true intersex condition with patients demonstrating considerable variability in physical exam findings, endocrinologic evaluation, and molecular genetics. Proper diagnosis of this condition is important with regard to counseling patients as to their future fertility. Chart Review - Retrospective We retrospectively reviewed the database of infertile male patients evaluated at our institution over the past 11 years. Six patients with 46,XX male syndrome were identified. Physical exam data, endocrinologic evaluation, and molecular genetic analysis were recorded for all patients. Testes biopsy was performed on two of six patients. All patients were found to have positive probes for the SRY sex-determining region with fluorescence in situ hybridization. Four of six patients were found to have translocation of SRY to the short arm of chromosome X. Two patients had cytogenetically evident translocation of a larger portion of chromosome Y including SRY (der(X)t(X;Y)(p22.3;p11.3)). Endocrinologic evaluation demonstrated elevated FSH (range 18.0-62.9 iU/L) and LH (range 7.4-22.5 iU/L) levels in all patients. Total testosterone levels were in the low-normal to normal range in all patients (range 226-625 ng/dL). In two patients undergoing testis tissue biopsy, no sperm were found on wet-prep examination. Final pathology demonstrated no evidence of spermatogenesis in either specimen. 46,XX male patients represent a small proportion of male patients evaluated for infertility; correct diagnosis of this condition and a true understanding of its implications are essential. This condition does not represent a variant of Klinefelter’s syndrome, as it has been previously termed elsewhere. In the 46,XX male syndrome, the presence of the SRY-determining region on the X choromosome of these patients accounts for their male phenotype. Without the remainder of the Ychromosome, however (specifically the AZF-a, AZF-b, and AZF-c regions), these patients cannot be expected to demonstrate any normal spermatogenesis. Others have described 46,XX males with absence of the SRY determining region, in addition to patients such as the ones above with a cytogenetically evident translocation der(X)t(X;Y)(p22.3;p11.3). Given this great variability in the molecular genetics of these patients, all male patients with a 46,XX karyotype should undergo FISH molecular analysis with SRY probe.