Impaired puberty, fertility, and final stature in 45,X/46,XY mixed gonadal dysgenetic patients raised as boys

Abstract

Context: Gender assignment followed by surgery and hormonal therapy is a difficult decision in the management of 45,X/46,XY patients with abnormal external genitalia at birth considering the paucity of studies evaluating pubertal development and fertility outcome, most notably for patients raised as boys. Objective: The purpose of this study was to describe the pubertal course of 20 45,X/46,XY patients born with ambiguous genitalia and raised as boys. Methods: This is a multicenter retrospective study. Results: Mean age at study was 25.6G2.4 years. Eighty-five percent of the patients presented a 'classical' mixed gonadal dysgenetic phenotype at birth. Puberty was initially spontaneous in all but three boys, although in six other patients, testosterone therapy was subsequently necessary for completion of puberty. Sixty-seven percent of the remaining patients presented signs of declined testicular function at the end of puberty (increased levels of FSH and low levels of testosterone and/or inhibin B). Moreover, an abnormal structure of the Y chromosome, known to alter fertility, was found in 10 out of 16 (63%) patients. Two patients developed testicular cancer. Half of the patients have adult penile length of !80 mm. Mean adult height is 156.9G2 cm, regardless of GH treatment. Conclusions: In summary, 45,X/46,XY children born with ambiguous genitalia and raised as boys have an altered pubertal course and impaired fertility associated with adult short stature, which should, therefore, be taken into consideration for the management of these patients.

The Clinical Manifestation and Genetic Evaluation in Patients with 45,X/46,XY Mosaicism

“…Previous studies suggest that the phenotype of patients with 45,X/46,XY mosaicism has no relationship with the proportion of 45,X cells observed not only in peripheral blood lymphocytes but also in the gonads [Lindhardt et al, 2012;Martinerie et al, 2012;Tosson et al, 2012;Li et al, 2013;Rosa et al, 2014]. Clinical variations and different gender assignments have been observed even among monozygotic twins [Costa et al, 1998;Tho et al, 2007].…”

A Rare Cause of Male Infertility: 45,X/46,XY Mosaicism

“…The risk of gonadal malignancy in individuals with 45,X/46,XY mosaicism has been reported to be 10–15% [6, 17]. However, the risk in males with normal phenotypes is not exactly known.…”

“…Cardiovascular or renal disorders and gonadal malignancies are often seen in these individuals. 45,X/46,XY patients often present with short stature [5, 6]. …”

45,X/46,XY mixed gonadal dysgenesis: A case of successful sperm extraction

“…Of these patients, 45% developed testicular failure necessitating testosterone replacement. 9 Among this cohort, 63% of patients were had Y chromosomal rearrangements that had previously been documented to impair fertility.…”