ABSTRACT
A 14-year-old boy with a 46,XY karyotype and persistent breast-3-stage gynecomastia is reported. The reproductive axis was investigated by standard laboratory methods and the androgen receptor (AR) gene was sequenced. Also, a literature review of phenotypes associated with the AR genetic variant p.Pro392Ser was performed. The boy presented with height in the upper normal range (+1.9 SDS) and normal body mass index (-0,3 SDS); pubertal development was PH5/G4 (mean testicular volume 15 mL; 0 SDS). Laboratory findings were normal for age and sex, except aromatization index (0.09; reference range 0.03-0.07). Analysis of the AR gene showed the single nucleotide variant c.1174C>T (p.Pro392Ser) in exon 1, leading to the diagnosis of minimal androgen insensitivity syndrome (AIS). This genetic variant is reported in other 8 patients with AIS and is associated with variable clinical phenotypes ranging from complete to partial and minimal AIS. To the best of our knowledge, this is the first adolescent in whom the p.Pro392Ser mutation is associated with isolated persistent gynecomastia. The underlying reason of phenotypic variability due to this AR mutation remains unknown. Persistent gynecomastia due to minimal AIS has been reported in few additional males with variable AR mutations. Since fertility troubles may occur in adult men with minimal AIS, early diagnosis can allow optimizing the clinical management.
