Genetic diagnosis in XY disorders of sex development

XY disorders of sex development (XY DSD) comprise a class of heterogeneous genetic entities that result in discrepancies between chromosomal, gonadal, and phenotypic sex due to a reduction in androgen synthesis or action. The chief categories of disorders include gonadal dysgenesis, disorders with reduced androgen production (biosynthetic defect – either alone or in conjunction with impaired glucocorticoid and/or mineralocorticoid synthesis), and insensitivity to androgen action. While conventional diagnostic modalities, encompassing karyotyping, biochemistry, radiology, and, in a few cases, diagnostic laparoscopy, help in formulating a provisional diagnosis, molecular genetic testing is key to arriving at a precise etiology. Besides ending the diagnostic uncertainty, a molecular diagnosis helps to predict the natural course in terms of pubertal development and potential for fertility, thus contributing to decisions on the gender of rearing; and guides on surveillance for extragenital features and the risk of recurrence in subsequent pregnancies. This paper broadly discusses the genetic basis of XY DSD, different modalities of genetic testing, and their utility and limitations.