Many people are unaware of a genetic condition called Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC), which is linked to the early onset of  symptomatic uterine fibroids in young women. The condition is caused by a defective Fumarate Hydratase (FH) gene. It is important to recognize that individuals experiencing symptomatic uterine leiomyomas at a younger age should be considered for genetic testing. This is crucial because HLRCC is not only associated with uterine fibroids but also carries a risk of developing renal cancer at a median age of 37 years old. Identifying HLRCC through genetic testing can facilitate early detection and appropriate management of both uterine fibroids and potential kidney cancer.

In women with the genetic condition HLRCC, uterine fibroids often occur in multiple locations within the uterus and can be large and numerous. Symptoms commonly associated with uterine fibroids in HLRCC include abnormal uterine bleeding, pelvic pain, and an enlarged uterus.

A study at the Johns Hopkins Medical Institution investigated the incidence and mutational profiles of Fumarate hydratase (FH)-negative leiomyomas in young women for early identification of hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. Researchers evaluated 153 cases of uterine leiomyomas in women up to 30 years old and found that 4.6% had loss of FH protein expression. Genetic testing showed that 86% of these FH-negative tumors had FH mutations, with 50% being germline mutations. The results suggest a relatively high rate of FH germline mutations in these young patients, indicating genetic rather than epigenetic regulation of the FH gene.

Young women with symptomatic uterine fibroids should be considered for germline Fumarate Hydratase testing to evaluate for HLRCC.

References:

1.) Liu C, Dillon J, Beavis AL, Liu Y, Lombardo K, Fader AN, Hung CF, Wu TC, Vang R, Garcia JE, Xing D. Prevalence of somatic and germline mutations of Fumarate hydratase in uterine leiomyomas from young patients. Histopathology. 2020 Feb;76(3):354-365. doi: 10.1111/his.14007. Epub 2020 Jan 13. PMID: 31564060.