HLRCC Syndrome is a rare condition that makes a person more likely to develop certain types of tumors. These tumors can be either benign (not cancerous) or malignant (cancerous).
People with HLRCC Syndrome may develop the following:
- Leiomyomas of the skin: benign tumors of the skin. They may be single or multiple and look like raised flesh-colored nodules.
- Leiomyomatosis of the uterus (uterine fibroids): benign tumors of the uterus with very low risk of becoming cancerous.
- Kidney tumors: includes tumors of different types ranging from papillary tumors to renal cell carcinoma (kidney cancer).
HLRCC Syndrome can be passed from an affected parent to his or her children. Not everyone with HLRCC Syndrome has the same issues, even among people in the same family.
HLRCC Syndrome is caused by changes in a gene known as fumarate hydratase (FH). Genes carry information that tell the cells of the body how to work. The FH gene tells the cells of the body how to make fumarate hydratase. Fumarate hydratase is a protein important for normal cell function.
Most people without HLRCC Syndrome carry two working copies of the FH gene in their cells. One copy of the FH gene is inherited from each parent. People with HLRCC Syndrome have one working copy of the FH gene and one changed copy of the FH gene in each cell of their body. The change in the FH gene causes the gene to stop working right. It is called an FH variant.
Most children with HLRCC Syndrome inherit an FH variant from a parent who also has the syndrome. Sporadic HLRCC Syndrome cases can result from new (de novo) variants in the FH gene. People with a de novo FH variant have no history of the syndrome in their family. In these cases, the change either happened in the egg or sperm cell when the child was formed or in one of the child’s cells during pregnancy. These children are the first in their families to have HLRCC syndrome.
No matter how they acquired the FH variant, people with HLRCC Syndrome have a 50% (or 1 in 2) chance of passing it on to each of their children. It is unknown how many people have HLRCC Syndrome. About 300 families around the world have been reported with HLRCC Syndrome.
As people with HLRCC Syndrome get older, the working copy of their FH gene often becomes changed within some of their cells. When both copies of the gene are changed, benign tumors or cancers can develop. The issues of people with HLRCC Syndrome can vary between families and among members of the same family.
People who are born with changes in both copies of their FH genes have a genetic condition called fumarate hydratase deficiency (FH deficiency). During infancy, patients with FH deficiency can have such issues as:
- Trouble feeding
- Low muscle tone
- Seizures
- Abnormal head size
- Various brain abnormalities
- Distinct facial features
FH deficiency is completely different than HLRCC Syndrome. If two people with HLRCC Syndrome have a child together, there is a 1 in 4 (25%) chance for each of their children to have FH deficiency. A genetic counselor can discuss this condition in more detail.
A doctor may suspect this diagnosis after looking at a person’s medical or family history. In most cases, a doctor or genetic counselor will ask questions about the person’s health and the health of other family members. Read more about genetic counseling and genetic testing.
Diagnosing this syndrome is usually done by sequencing the FH gene to find variants (changes in the gene).
Genetic testing does not always find a variant that is responsible for the syndrome. A person can still have the syndrome, even if no variants in these genes are found. There are likely to be more undiscovered genes that play a role in the development of this syndrome.
Most of the cancer related to HLRCC Syndrome occurs in adults. Even so, some cases of kidney cancer have been reported in children with HLRCC Syndrome. The risk of developing kidney cancer in people younger than 20 is 1–2%. Lifetime risk of kidney cancer in people with HLRCC Syndrome is 10–16%. Typically, kidney cancers in HLRCC Syndrome are aggressive and often have spread to other parts of the body. For this reason, finding and treating kidney cancer early in people with HLRCC Syndrome leads to better outcomes.
The skin tumors (cutaneous leiomyomas) related to HLRCC Syndrome usually develop during the teen years. Most skin leiomyomas are not cancerous, but some can develop into a type of cancer called leiomyosarcoma.
Adults with HLRCC Syndrome are also at a higher risk of developing skin tumors and, in females, uterine tumors. Women with HLRCC Syndrome usually develop uterine fibroids in their 30s. Often, these tumors are removed to treat anemia resulting from excessive blood loss.
Some people with HLRCC Syndrome also have a slightly increased risk for certain nerve cell tumors (paragangliomas) and adrenal gland hormone-secreting tumors (pheochromocytomas). HLRCC patients with an increased risk of these types of tumors usually have specific changes in their FH genes or have a family history of those tumor types.
Doctors also have seen other types of cancer in people with HLRCC Syndrome, but the connection with HLRCC Syndrome is still being researched.
Cancer screening involves tests to check for cancer before symptoms occur. The goal is to find cancer at the earliest and most treatable stage. Guidelines for cancer screening are available online. Recommended screenings may change over time as doctors learn more about this syndrome, so these screening tests should be discussed with a health care provider who knows this syndrome well.
Other ideas to reduce the risk of cancer include:
- Eat a healthful diet with lots of fruits and vegetables
- Get regular exercise
- Avoid smoking or using tobacco products
- Avoid secondhand smoke
- Avoid excess sun exposure and always wear sunscreen, hat, and protective clothing when out in the sun
- Get medical attention for unusual or ongoing symptoms
Because of the medical concerns related to this syndrome, specialists in the following areas may need to assess a person with HLRCC Syndrome:
- Dermatology
- Gynecology (for women)
Resources about HLRCC:
- HLRCC Family Alliance (www.hlrccinfo.org)
- Kidney Cancer Association (www.kidneycancer.org)
- National Uterine Fibroids Foundation (nuff.org)
Other resources:
- Making Sense of Your Genes: A Guide to Genetic Counseling (ncbi.nlm.nih.gov/books/NBK115508/)
Adapted from educational materials developed by the St. Jude Children’s Research Hospital Cancer Predisposition Program