Hereditary Leiomyomatosis and Renal Cell Cancer syndrome and the FH gene

Hereditary Leiomyomatosis and Renal Cell Cancer syndrome (HLRCC)

Hereditary Leiomyomatosis and Renal Cell Cancer syndrome (HLRCC) is caused by mutations in the FH gene.

Both men and women with HLRCC tend to develop cutaneous leiomyomas, usually in their 20s and 30s. These flesh-coloured lesions can be solitary or multiple, ranging in size from several millimetres to 1 cm. They are fixed to skin but moveable and may coalesce to form plaques. They are most commonly found on extensor extremities, the trunk and the face and neck.

Cutaneous leiomyomas are painful in around 90% of individuals, either spontaneously or secondary to cold, pressure, or emotion. Different treatments exist, including surgical removal although recurrence is common.

Women with HLRCC have a very high lifetime likelihood of developing fibroids (uterine leiomyomas), with more than half requiring either myomectomy or hysterectomy in their mid-30s to control symptoms such as menorrhagia. Symptomatic fibroids should be managed in the usual manner. While transformation of leiomyomas to leiomyosarcoma (a rare cancer) has been described, the likelihood is low.

In addition, men and women who carry an FH mutation have an increased lifetime risk of kidney cancer (10 to 16%). These cancers are usually Type 2 Papillary renal cell cancers, tend to be aggressive and can metastasise(spread) when very small. The average age of onset is 44 but isolated cases have occurred in children. As a result, screening with MRI is recommended annually from age 15. Note: CT scans and ultrasounds are not sensitive enough to detect small cancers.

Does this sound like you or your family? Do you have clinical signs of Hereditary Leiomyomatosis and Renal Cell Cancer syndrome or has an FH gene mutation been detected in a blood relative? Make an appointment with Dr Hilda High at Sydney Cancer Genetics. It is a confidential opportunity to discuss your personal and family history of cancer and genetic testing can be organised, if needed.

These links may be useful

  • Because it is a rare syndrome, there is no specific Australian based support group for Hereditary Leiomyomatosis and Renal Cell Cancer syndrome. Rare Connect is an international group helping to connect patients with rare diseases globally.
  • The Cancer Genetics section of the Cancer Institute's eviQ website provides up-to-date Australian-based management guidelines
  • The US National Library of Medicine website has more information about this syndrome.