Preserved fertility in a non-mosaic Klinefelter patient with a mutation in the fibroblast growth factor receptor 3 gene: case report

Abstract

Patients with Klinefelter syndrome (47,XXY) are characterized by eunuchoid body proportions, gynaecomastia, small firm testes and azoospermia. We describe a Klinefelter patient (non-mosaic 47,XXY karyotype) who was heterozygous for the classical 1138G>A mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, which is a gain-of-function mutation resulting in achondroplasia. The patient had phenotypic characteristics of achondroplasia (e.g. short limbed dwarfism and frontal bossing). Testicular volume was 8 ml at 27 years of age and repeated semen samples showed sperm concentrations of 0.175 million/ml. Serum FSH levels were elevated (21.7 IU/l) compared to normal age-matched healthy male controls and patients with non-mosaic Klinefelter syndrome, and inhibin B levels were low-normal, in contrast to the usually undetectable inhibin B levels in adult Klinefelter patients. The patient fathered a child from a spontaneous pregnancy. The observed testicular size and function in our patient contrast the typical findings in classical Klinefelter syndrome. We speculate that the alteration of FGFR3 protein function in our Klinefelter patient alleviated the destruction of the seminiferous tubules and may suggest that the fibroblast growth factor family has a pleiotrophic function in human spermatogonia, which physiologically express FGFR3.