Hereditary Leiomyomatosis and Renal Cell Cancer

Approved by the Cancer.Net Editorial Board, 04/2020

What is hereditary leiomyomatosis and renal cell cancer?

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary condition associated with the development of multiple leiomyomas (smooth muscle tumors) in the skin and uterus (fibroids) as well as an aggressive form of kidney cancer. HLRCC can look different in patient to patient, ranging from mild to severe. These skin tumors generally develop in adulthood and occur on chest, back, arms, and legs. These tumors can be painful, but they are not cancerous. Women with HLRCC can develop uterine fibroids as young as their teens or early 20s. Kidney cancers most often occurs in adulthood but has been described in young children and teenagers.

What causes HLRCC?

HLRCC is a genetic condition. This means that the risk of cancer and other features of HLRCC can be passed from generation to generation in a family. A specific gene called the fumarate hydratase (FH) gene is believed to cause all known cases of HLRCC. Research is ongoing to learn more about this condition.

How is HLRCC inherited?

Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. If both copies of FH are damaged from hereditary mutation, death usually occurs within the first few years of life from a condition known as Fumarase Deficiency.

HLRCC follows an autosomal dominant inheritance pattern, in which a mutation (alteration) happens in only 1 copy of the gene. This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation. However, if the parents test negative for the mutation (meaning each person’s test results found no mutation), the risk to the siblings significantly decreases but their risk may still be higher than the average risk.

Current research shows that a person with HLRCC must have a second mutation in normal copy of the FH gene in order for a tumor to appear. In these cases, a person is generally born with 1 mutated gene (the autosomal dominant inheritance pattern described above; also called a germline mutation) and then acquires a mutation in the second copy of the FH gene at some point during his or her lifetime in skin, uterus, or kidney cells (called a somatic alteration). Then, with both copies of the FH gene altered, the body loses its ability to suppress tumor growth.

Options exist for people interested in having a child when a prospective parent carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to reduce the likelihood that their children will inherit the condition. For more information, talk with an assisted reproduction specialist at a fertility clinic.

How common is HLRCC?

HLRCC was once considered rare, but with increased use of germline testing, it is becoming clear that the condition is more common than once believed. The number of people and families who have this condition is unknown.

How is HLRCC diagnosed?

HLRCC is suspected when a person has a history of multiple skin leiomyomas. A family history of fibroid tumors, particularly early in life, and an aggressive form of kidney cancer (known as HLRCC or FH-deficient kidney cancer). Tumors can resemble papillary type 2, collecting duct, or tubulocytic forms of kidney cancer. Germline genetic testing to look for mutations in the FH gene is available for people suspected of having HLRCC.

What are the estimated cancer risks associated with HLRCC?

HLRCC is associated with an increased risk of renal cell carcinoma. For people with HLRCC, the estimated risk for this type of kidney cancer has been estimated around 15% to 30%, but the penetrance, or appearance, of this particular sign of HLRCC may be lower than that, as more people are diagnosed with this increasingly recognized condition.

What are the screening options for HLRCC?

There are no specific screening guidelines to diagnosis HLRCC.

The most common screening options for those with a diagnosis of HLRCC are regular skin examinations and cross-sectional imaging studies of the kidney with contrast, which is a special dye. Imaging may include a computed tomography (CT) scan, which is a 3-dimensional picture of the inside of the body using an x-ray or a magnetic resonance imaging (MRI) every year. As an MRI uses magnetic fields, not x-rays, there is no radiation and therefore has been the preferred imaging modality. If a suspicious kidney lesion is found, other scans – such as a chest CT scan, a renal ultrasound, or a positron emission tomography-computed tomography scan (PET-CT) –may also be done to learn more about the suspicious area.

Also, women should have regular gynecological examinations and imaging studies such as an ultrasound to look for uterine fibroids, unless the uterus has been removed previously in a hysterectomy.

Screening guidelines may change over time as new technologies are developed and more is learned about HLRCC. It is important to talk with your health care team about appropriate screening tests.

Learn more about what to expect when having common tests, procedures, and scans.

Questions to ask the health care team

If you are concerned about your risk of cancer, talk with your health care team. It can be helpful to bring someone along to your appointments to take notes. Consider asking your health care team the following questions:

  • What is my risk of developing kidney cancer?

  • What can I do to reduce my risk of cancer?

  • What are my options for cancer screening?

If you are concerned about your family history and think your family may have HLRCC, consider asking the following questions:

  • Does my family history increase my risk of developing kidney cancer?

  • Are the skin lesions or uterine tumors in me or my family considered leiomyomas?

  • Does my medical family history suggest the need for a cancer risk assessment?

  • Will you refer me to a genetic counselor or other genetics specialist?

  • Should I consider genetic testing?

Related Resources

The Genetics of Cancer

Genetic Testing

What to Expect When You Meet With a Genetic Counselor

Collecting Your Family Cancer History

Sharing Genetic Test Results with Your Family

Family Genetic Testing Q&A

More Information

Hereditary Leiomyomatosis and Renal Cell Cancer Family Alliance

National Cancer Institute

To find a genetic counselor in your area, ask your health care team or visit the following website:

National Society of Genetic Counselors