45X46XY

45X46XY, often described as 45,X/46,XY mosaicism, is a sex chromosome mosaic condition in which some cells carry a single X chromosome (45,X) and others carry both an X and a Y chromosome (46,XY). This pattern arises after fertilization through postzygotic loss or nondisjunction of sex chromosomes during early embryonic cell divisions, resulting in two distinct cell lines within the same individual. The proportion and distribution of the two lines vary by tissue, making the clinical features highly variable.

Clinical presentation ranges widely. Some individuals have Turner-type features with gonadal dysgenesis or streak gonads and may present with short stature, congenital lymphedema, or congenital heart and renal anomalies. Others may have predominantly male phenotype, with ambiguous genitalia or normal male development, depending on the relative contribution of each cell line. The variability can complicate prediction of outcomes based on karyotype alone.

Diagnosis is usually made by karyotype analysis of peripheral blood, but mosaicism can be tissue-specific, so abnormalities may not be detected in all tissues. Additional testing (such as testing of other tissues or targeted genetic analyses) may be used to assess the extent of mosaicism and gonadal tissue.

Management requires a multidisciplinary approach. Key considerations include monitoring growth and puberty, addressing any Turner-associated health issues, and evaluating gonadal tissue. There is an elevated risk of gonadal tumors in individuals with Y chromosome material and dysgenetic gonads, so clinicians may discuss surveillance strategies or prophylactic gonadectomy in selected cases. Fertility is typically limited, and hormone therapies may be used to support pubertal development. Genetic counseling is advised, noting that most cases arise de novo and recurrence risk is generally low.