Fiorini Aureliano, Sepich Margherita, Pontrelli Margherita, Sangriso Giorgio, Cosci O Di Coscio Mirna, Lauletta Marcella, Baldinotti Fulvia, Peroni Diego, Ambrosio Maria Rosaria, Bertelloni Silvano
Division of Pediatrics, Department of Obstetrics, Gynecology and Paediatrics, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Sex Dev. 2020;14(1-6):21-26. doi: 10.1159/000514067. Epub 2021 Mar 10.
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.
报告了一名14岁男孩，核型为46,XY，患有持续性3期男性乳腺增生症。通过标准实验室方法对生殖轴进行了研究，并对雄激素受体（AR）基因进行了测序。此外，还对与AR基因变异p.Pro392Ser相关的表型进行了文献综述。该男孩身高处于正常范围上限（+1.9 SDS），体重指数正常（-0.3 SDS）；青春期发育为PH5/G4（平均睾丸体积15 mL；0 SDS）。除芳香化指数外（0.09；参考范围0.03 - 0.07），实验室检查结果在年龄和性别方面均正常。AR基因分析显示外显子1存在单核苷酸变异c.1174C>T（p.Pro392Ser），从而诊断为轻度雄激素不敏感综合征（AIS）。在其他8例AIS患者中也报告了这种基因变异，它与从完全性到部分性和轻度AIS的多种临床表型相关。据我们所知，这是首例p.Pro392Ser突变与孤立性持续性男性乳腺增生症相关的青少年。这种AR突变导致表型变异的潜在原因尚不清楚。在少数其他具有不同AR突变的男性中也报告了因轻度AIS导致的持续性男性乳腺增生症。由于成年轻度AIS男性可能出现生育问题，早期诊断有助于优化临床管理。
