Complete Androgen Insensitivity Syndrome (CAIS) Genetic Counseling: Navigating Germline Mosaicism Concerns

Complete androgen insensitivity syndrome (CAIS) is caused by pathogenic variants in the androgen receptor (AR) gene that lead to a phenotypically female appearance in XY individuals. It is almost always inherited as an X-linked recessive condition. Here, we present two sisters with different clinical courses. AR gene sequencing revealed identical hemizygous pathogenic variants in both sisters but not in the mother. This rare occurrence of germline mosaicism is the first described in CAIS. Germline mosaicism should be considered when "de novo" AR gene variants are identified. Despite the low recurrence risk, counseling would be beneficial to families so they can make well-informed prenatal and reproductive plans.