Male infertility associated with hereditary leiomyomatosis and renal cell carcinoma

Abstract

To report a novel association between a cancer predisposition syndrome (hereditary leiomyomatosis and renal cell carcinoma [HLRCC]) and male infertility. Case report. University medical center adult genetics clinic. A 31-year-old male of Chinese ancestry referred for evaluation of immotile sperm. Physical examination, family history assessment, genetic testing, and cancer screening. Genetic testing results. Physical exam: cutaneous leiomyomata on the upper back and left arm. Family history: the patient has a sister with uterine leiomyomata. Genetic testing revealed a mutation in the fumarate hydratase gene, which codes for an enzyme (fumarase) that has previously been implicated in sperm number and motility. More recently, heterozygous mutations in this gene have been associated with HLRCC. However, male infertility is not a recognized manifestation of this condition. A comprehensive medical (including family) history and physical examination are important when evaluating male infertility. Genetics consultation enabled our patient and his family to begin appropriate cancer screening and provided reproductive options, including prenatal/preimplantation diagnosis. Further studies of the relationship between fumarase, HLRCC, and male infertility are needed to provide accurate counseling to families and to better understand genotype-phenotype correlations.