A 22-year-old male was referred for management of 45,X/46,XY mosaicism, diagnosed prenatally on amniocentesis (96% 45,X, 4% 46,XY). He had male genitalia at birth and short stature (3rd centile). Bilateral orchidopexy at age 4 revealed markedly reduced germ cells and ovarian-type stroma in the left testis.
He was initiated on testosterone at 14 for delayed puberty (Tanner stage II, testes 3–5 mL), progressing to Tanner stage IV by 17 (testes 12–15 mL). Adult height was 160 cm, below mid-parental height (172 cm).
At age 24, semen analysis showed azoospermia. Sperm extraction was offered but declined. He currently has no partner or fertility plans.
Surveillance followed adapted Turner syndrome guidelines. Cardiac imaging identified a bicuspid aortic valve with mild regurgitation but stable aortic dimensions. Renal and testicular ultrasounds were normal. Bone density scan revealed osteopaenia (lumbar Z-score -1.1; femoral neck -1.9). Secondary osteoporosis screen was negative.
He attends annual endocrinology review.
Discussion Summary
45,X/46,XY mosaicism is a rare sex chromosome disorder affecting both males and females. Despite male phenotype, affected individuals share comorbidity profiles with Turner syndrome—including increased mortality risk, cardiac anomalies, thyroid disease, metabolic syndrome, and osteoporosis. Most males undergo spontaneous puberty but are infertile due to Sertoli-cell-only histology and elevated gonadotropins.
Tumour risk remains elevated, even with normal male genitalia, due to Y chromosome-linked oncogenes (e.g., TSPY) and dysgenetic gonads. Up to 36% may have histologically detected gonadal neoplasia. Surveillance should include annual ultrasound and consider post-pubertal gonadal biopsy.
These individuals are often under-investigated and under-recognised. Coordinated multidisciplinary care is essential to address endocrine, cardiac, fertility, and psychosocial health.