Congenital adrenal hyperplasia (CAH) is a genetic condition in which an enzyme defect causes excessive production of hormones from the adrenal glands such as testosterone. Girls with this condition can be born with ambiguous genitalia (genitalia that look as either male or female). Patients with CAH often require hormonal therapy, and some girls require surgical intervention for correction of the genito-urinary abnormalities.
Androgen insensitivity (partial or complete), also known as PAIS or CAIS, respectively, is a rare genetic condition in which XY individuals are partially or completely insensible to testosterone effects. The spectrum of this disorder is wide and ranges from ambiguous genitalia to complete female appearance. Patients affected by this condition require hormonal therapy during pubertal and adult years and they also require surgical intervention for removal of gonads (testicles).
5-alpha reductase deficiency is a genetic condition in which an enzyme defect results in decreased conversion of testosterone into its more active metabolite, dihydrotestosterone (DHT). Males affected with this condition have ambiguous genitalia. Patients with 5-alpha reductase are often undiagnosed for years until masculinization of the external genitalia is noticed during pubertal years. Patients with this condition often require hormonal treatment as well as surgery of the external genitalia.
Leydig cell hypoplasia/aplasia is a genetic condition which affects the cells that produce testosterone in the testes. Males affected with this condition can have ambiguous genitalia due to low testosterone levels, since normal amounts of this hormone are essential for the formation of male external genitalia. Patients with this condition often require hormonal replacement therapy.
Gonadal dysgenesis is a category of disorders which encompasses abnormalities of gonad (testicle or ovary) development or differentiation, leading to a discordance between sex chromosomes, gonads and internal/external genitalia formation. There are different types of gonadal dysgenesis, namely, total, partial or mixed, depending on the sex chromosomes (XX, XY or XX+XY) and gonadal (ovarian/testicular) tissue. Gonadal dysgenesis is a genetic disorder, but the precise genetic abnormality cannot be documented in most cases. Depending on the type of gonadal dysgenesis, patients with this condition may require hormonal and/or surgical intervention.
Mullerian duct abnormalities include disorders such as persistent Mullerian duct syndrome. The Mullerian duct gives rise to Mullerian structures (fallopian tubes, uterus, cervix and upper third of the vagina), which normally regress during the formation of the male fetus. Persistent Mullerian duct syndrome is a genetic condition in which there is lack of a hormone known as anti-Mullerian hormone (AMH). Affected males have normal male reproductive organs and normal male external genitalia but also have a uterus and fallopian tubes which fail to regress due to the lack of AMH. Patients with this condition often have undescended testes and the Mullerian structures are seen during surgery for correction of the undescended testes. The Mullerian structures are often removed. Patients with this condition don’t typically require hormonal therapy.
Aromatase deficiency is a genetic disorder in which an enzyme (aromatase) responsible for conversion of androgens (hormones such as testosterone) into estrogen has reduced function. This causes females to have higher levels of testosterone leading to ambiguous genitalia and also causes lack of menstrual periods in the pubertal years due to low levels of estrogen. Patients with this condition typically need hormonal therapy and may need surgical correction of the ambiguous genitalia.