A 46,XX Karyotype in Men with Infertility: Two New Cases and Review of the Literature

46,XX male sex reversal syndrome is a rare genetic cause of male infertility. We report on two new cases of this syndrome in men presenting with hypogonadism and infertility. Cytogenetic and molecular analysis was performed in both patients. An extensive review of the literature for 46,XX male sex reversal syndrome cases related to infertility was also performed to fully characterise this syndrome. Genetic analyses showed translocation of the SRY on Xp chromosome and complete absence of all Azoospermia factor (AZF) genetic regions. All patients included in the review presented hypergonadotropic hypogonadism. Small testes were the most common clinical characteristic present in 90.2% of the patients, followed by small penis (31.8%), gynecomastia (26.8%) and poor hair distribution (15.4%). The presence of the SRY was identified in 130/154 (84.4%) patients: in 98.5% of cases, it was translocated on the Xp chromosome and in 1.5% on an autosome. All patients were azoospermic, due to the lack of AZF genetic regions. Males with normal phenotype and primary hypogonadism should be properly evaluated by the physicians and must be referred for cytogenetic and molecular analysis to exclude or confirm 46,XX male sex reversal syndrome. More cases of this syndrome with SRY translocated on an autosome are needed to identify if these patients have different characteristics than those with SRY translocated on Xp chromosome. Whole genome analysis of these patients is required to elucidate the genetic differences which are responsible for the phenotypic variability of the syndrome.