SNP Shot: Genomic Insights

Androgen insensitivity syndrome (AIS) is a condition affecting sexual differentiation before birth and during puberty. Individuals with AIS are genetically male, possessing one X and one Y chromosome in each cell. However, their bodies are unable to properly respond to androgens, which are male sex hormones. This can result in predominantly female external sex characteristics, or signs of both male and female sexual development.

Complete androgen insensitivity syndrome (CAIS) occurs when the body is completely unresponsive to androgens. Individuals with CAIS have female external sex characteristics, but lack a uterus, resulting in infertility and the absence of menstruation. They are typically raised as females and identify as female. Internally, they possess undescended testes located in the pelvis or abdomen. These testes carry a small risk of becoming cancerous if not surgically removed. People with CAIS also often have minimal or absent pubic and underarm hair.

Partial and mild forms of androgen insensitivity syndrome occur when the body's tissues have some sensitivity to androgens. Individuals with partial androgen insensitivity (PAIS), sometimes called Reifenstein syndrome, may exhibit typically female, mixed (both male and female), or typically male genitalia. They may be raised as either males or females and identify as either male or female. Those with mild androgen insensitivity typically have male sex characteristics at birth, but are often infertile and may develop enlarged breasts (gynecomastia) during puberty.

Inheritance:

AIS is inherited in an X-linked recessive manner. This means the gene responsible for the condition is located on the X chromosome, one of the sex chromosomes. Males, having only one X chromosome, will develop the condition if they inherit one altered copy of the gene. Females, with two X chromosomes, must inherit a mutation on both copies to be affected. Therefore, X-linked recessive disorders are more common in males. Approximately two-thirds of AIS cases are inherited from mothers who are carriers, possessing an altered copy of the AR gene on one of their X chromosomes. The remaining cases arise from a new mutation in the mother's egg cell before conception or during early fetal development.