Persistent Müllerian structures in an infant with complete androgen insensitivity syndrome

Abstract

Abstract Complete androgen insensitivity syndrome (CAIS) is a variation in sex characteristics that occurs due to a pathogenic loss-of-function variant in the androgen receptor gene. CAIS classically presents as an individual with 46,XY karyotype, apparent female external genitalia, a blind-ending vaginal pouch, internal testes, and absence of Müllerian structures; however, there are case reports describing Müllerian remnants in CAIS with unclear underlying pathophysiology. We describe a case of a 46,XY infant with CAIS and a uterus on postnatal imaging. Genetic testing revealed a hemizygous pathogenic androgen receptor (AR) gene variant and 2 variants of unknown significance in CYP11B1 and WNT4, which offer theoretical mechanisms for persistent Müllerian structures. Management included multidisciplinary care with counseling around sex assignment and anticipatory guidance regarding gonadal surveillance, gender identity, and future puberty. This case contributes to the limited literature on atypical phenotypes in CAIS demonstrating the need for further research into the underlying genetic and pathophysiologic mechanisms of this condition.