45,X/46,XY mixed gonadal dysgenesis

45,X/46,XY mixed gonadal dysgenesis (MGD) is a rare disorder of sex development (DSD) caused by mosaicism in which some cells have a single X chromosome (45,X) and others have a normal male sex chromosome complement (46,XY). This chromosomal mosaicism leads to abnormal development of the gonads and variable phenotypic presentation. The condition is also referred to as 45,X/46,XY mosaicism or mixed gonadal dysgenesis. Affected individuals typically have asymmetric gonadal development, most commonly a dysgenetic (streak) gonad on one side and a testis or dysgenetic testis on the other. External genitalia can range from typically female to ambiguous to typically male, depending on the degree of testicular function during fetal development. Key clinical features include ambiguous genitalia at birth, short stature (related to the 45,X cell line, similar to Turner syndrome), and an increased risk of gonadal tumors, particularly gonadoblastoma, especially in dysgenetic gonads containing Y chromosome material. Internal genital structures are also variable and may include a uterus, fallopian tubes, or Wolffian duct derivatives depending on local gonadal hormone production. Some individuals may also exhibit features associated with Turner syndrome, such as webbed neck, lymphedema, cardiac anomalies (particularly coarctation of the aorta), and renal malformations. Management of 45,X/46,XY mixed gonadal dysgenesis requires a multidisciplinary approach involving endocrinologists, urologists, gynecologists, psychologists, and geneticists. Treatment decisions are individualized and may include hormone replacement therapy (estrogen or testosterone depending on sex of rearing), surgical management of ambiguous genitalia, and prophylactic gonadectomy of dysgenetic gonads to reduce the risk of gonadoblastoma. Growth hormone therapy may be considered for short stature. Long-term monitoring for gonadal tumors, cardiovascular health, and psychosocial well-being is essential. Early genetic counseling and psychological support are important components of care for affected individuals and their families.

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