Prepubertal Metformin Treatment in Fragile X Syndrome Alleviated Macroorchidism: A Case Study

The majority of males with Fragile X syndrome (FXS) have macroorchadism in addition to intellectual and language deficit, behavioral problems and autism. Macroorchidism is a characteristic feature of FXS and it is present in more than 90% of postpubertal males. The results of preclinical studies demonstrated that antidiabetic drug metformin rescues multiple phenotypes of FXS in both the Drosophila and mouse models including the presence of macroorchidism. Preliminary studies of patients with FXS demonstrated language and behavioral improvements. Here, we present one case of a male with FXS who has been treated with metformin clinically from 12 to 14 years of age. He was Tanner stage 3 at age 14 and his testicular volume was in the normal range which is rare in FXS. This is the first report of the alleviation of macroorchidism in a male with FXS treated with metformin and it parallels the changes seen with metformin in the mouse model of FXS.