Objective: To establish the diagnosis of complete androgen insensitivity syndrome (CAIS) in two patients with characteristic clinical and hormonal findings, relative family history in one of them, and unusual Müllerian remnants in the other.
Design: Case report.
Setting: Research laboratory in the Department of Medical Genetics at a university children's hospital.
Patient(s): Two patients with 46,XY sex reversal and two maternal aunts of the first patient with the same clinical condition were tested.
Intervention(s): Bilateral gonadectomy was performed on both patients.
Main outcome measure(s): Genetic counseling, cancer prophylaxis, hormone substitution therapy.
Result(s): Molecular analysis revealed two novel mutations, a frameshift familial (c.2494delA) in patient 1 and a missense sporadic (c.T3004C) in patient 2. The c.2494delA mutation was also detected in two of the three affected maternal aunts of patient 1. Patient 2 presents an unusual persistence of Müllerian structures.
Conclusion(s): Genetic counseling of potential women carriers of androgen receptor (AR) mutations is crucial for the early diagnosis of the affected offspring. The presence of Müllerian remnants, although rare, should not exclude the diagnosis of CAIS. Both identified mutations are novel and provide further evidence for the correlation between specific AR mutations and phenotype.