Disorders of Sexual Development

Family Tree
Inheritance pattern of a genitourinary birth defect over five generations of a family.

Disorders of sexual development (DSD) are a group of varied conditions, all of which involve alterations in embryonic development and/or sex hormones. These anomalies cause mismatches between the blood karyotype, the gonads, and the internal and/or external genitalia.

Internal and external genitalia are masculinized or feminized by critically-timed activation of genes and hormones. These factors trigger the gonad to mature to either an ovary, testis, undifferentiated gonad, streak gonad, dysgenetic gonad, or ovotestis.

A normal embryonic testis makes sex hormones (insulin-3, testosterone, and Müllerian inhibiting substance) that act on the hormonally responsive internal and external genitalia to cause them to masculinize. In contrast, a normal embryonic ovary does not make these sex hormones, leading to feminization of the internal and external genitalia.

In many DSD cases, we can perform DNA tests and find the cause. However, some DSD cases remain unsolved. By studying the unsolved cases or affected families, we hope to discover unknown genes regulating sexual development.