Abstract

Introduction: Complete Androgen Insensitivity Syndrome (CAIS) is caused by mutations in the androgen receptor gene (AR), leading to androgen resistance. Early recognition is crucial for management.Toevaluate clinical presentations, hormonal profiles, genetic characteristics, and decisions regarding gonadectomy in pediatric CAIS. Factors influencing gonadectomy, including malignancy risk, gonadal function, and psychological well-being were assesed.

Material and methods: Medicalrecords of 16 children genetically confirmed CAIS patients, aged 3 days–18 years, diagnosed between 2004 and 2024 at a tertiary referral centerwere retrospectively reviewed. Clinical, hormonal, genetic, and histological data were analyzed.

Results: Twelve patients (75%) were diagnosed prepubertally, most commonlydue to inguinal hernia. Familial recurrence occurredin 4 cases (25%). Novel pathogenic AR variants not previously reported in public databases were identified in three patients.Prepubertal patients with hormone data (n=5) demonstratedAMH >150 pM. Pubertal patients (n=9) had markedly elevated testosterone levels [median at 1361.3 ng/dl, range 367-3460 ng/dl]. Gonadal biopsy was performed in 3 cases (19%). Gonadal preservation was recommended in 11 children (69%), while 5 (31%) underwent gonadectomy followed by estrogen replacement therapy.

Conclusions: Most CAIS cases in this pediatric cohort were detected early through inguinal hernia or family screening. Delayed gonadectomy allowed spontaneous pubertal development and feminization. While gonadectomy results in lifelong hormone dependence and may raise identity-related concerns, surveillance-based gonadal preservation appears safe during childhood. The identification of novel AR variants expands the mutational spectrum of CAIS and highlights the need for multicenter registries and improved biomarkers to optimize individualized care.