SNP Shot: Genomic Insights

Aromatase deficiency is a disorder marked by low estrogen levels and elevated testosterone levels.

Females with this deficiency have a standard female chromosome arrangement (46,XX), but at birth, their external genitalia may be neither distinctly female nor male (ambiguous genitalia). Their internal reproductive organs are usually normal, but ovarian cysts develop early in life, disrupting ovulation. During adolescence, most affected females do not experience typical female development, such as breast development and menstruation. Acne and excessive hair growth (hirsutism) are common.

Males with aromatase deficiency have a typical male chromosome arrangement (46,XY) and are born with male external genitalia. Some affected men may experience reduced libido, abnormal sperm production, or have small or undescended testes (cryptorchidism).

Aromatase deficiency can also manifest in features affecting both sexes. Excessive long bone growth in the arms and legs leads to abnormal height. This abnormal bone growth also causes delayed bone age and osteoporosis, increasing the risk of fractures from minor injuries. Affected individuals may also exhibit insulin resistance, leading to high blood sugar (hyperglycemia). Weight gain and fatty liver are also associated with this deficiency.

Pregnant women carrying fetuses with aromatase deficiency may experience mild symptoms of the condition, even if they themselves are unaffected. These symptoms can include hirsutism, acne, clitoromegaly, and a deepened voice. These features may appear as early as the 12th week of pregnancy and resolve shortly after childbirth.

Inheritance:

Aromatase deficiency follows an autosomal recessive inheritance pattern. This means that both copies of the aromatase gene in each cell must have mutations for the condition to develop. Individuals with only one copy of the mutated gene (carriers) usually do not exhibit any signs or symptoms of the condition.