Hereditary Leiomyomatosis and Renal Cell Carcinoma (2024)

Also called: HLRCC syndrome, Reed’s syndrome, HLRCC, FH tumor predisposition syndrome, multiple cutaneous and uterine leiomyomatosis (MCL/MCUL)

Hereditary leiomyomatosis and renal cell carcinoma is a rare genetic condition that makes a person more likely to develop certain types of tumors. These tumors include kidney tumors and skin tumors. The tumors can be cancerous (malignant) or not cancerous (benign).

People with HLRCC may develop:

  • Noncancerous tumors on the skin. These tumors look like bumps or nodules. They may be the same color as the skin, or they may be darker.
  • Growths (fibroids) of the uterus in women

HLRCC can pass from a parent to a child. Not everyone with HLRCC has the same symptoms, even if they are in the same family.

Cancer risk with HLRCC

The risk of developing kidney cancer in patients younger than 20 is 1–2% (1–2 in 100). The lifetime risk of kidney cancer in patients with HLRCC is 10–16% (10–16 in 100). Kidney cancers in HLRCC usually grow quickly and spread to other parts of the body. It is important to find and treat kidney cancer early. This leads to better outcomes.

Most tumors related to HLRCC occur in adults. Some cases of kidney cancer have been reported in children with HLRCC.

The skin tumors related to HLRCC usually develop during adolescence. Most are not cancerous. Some can develop into a type of cancer called leiomyosarcoma.

Adults with HLRCC are at a higher risk of skin tumors. Females have a high risk of tumors of the uterus. Uterine fibroids usually develop around age 30. Often, these tumors are removed to treat anemia from heavy blood loss.

Some HLRCC patients also have an increased risk for certain nerve cell tumors (paragangliomas) and adrenal gland hormone-secreting tumors (pheochromocytomas). HLRCC patients with an increased risk of these tumors usually have specific changes in their FH genes. Some patients have a family history of those tumor types.

Doctors have also seen other tumor types in patients with HLRCC. The connection with HLRCC and these tumors is still being studied.

Causes of HLRCC

HLRCC is caused by changes in the fumarate hydratase (FH) gene. Genes carry information telling cells in the body how to function. The FH gene tells the cells how to make fumarate hydratase. Fumarate hydratase is a protein important for normal cell function. When a gene change causes a disorder or disease, it is called a gene mutation.

People with HLRCC have 1 working copy of the FH gene and 1 changed copy. The change in the FH gene causes the gene to stop working properly. It is called an FH mutation.

How HLRCC is inherited

Most children with HLRCC inherit an FH mutation from a parent who also has HLRCC.

Some HLRCC cases happen due to new mutations in the FH gene that were not passed down from a parent. People with a new FH mutation have no history of HLRCC in their family. In these cases, the change happened in either the egg or the sperm cell when the child was formed. Or the change occurred in 1 of the child’s cells early in development. These children are the first in their families to have HLRCC.

People with HLRCC have a 50% (1 in 2) chance of passing the FH mutation to each of their children.

As people with HLRCC get older, the working copy of their FH gene may become changed within some of their cells. When both copies of the gene are changed, noncancerous tumors or cancers can develop.

The features of people with HLRCC can vary even with people in the same family.

Fumarate hydratase deficiency (FH deficiency)
People who are born with changes in both copies of their FH genes have a different genetic condition called fumarate hydratase deficiency (FH deficiency or fumaric aciduria). As infants, patients with FH deficiency can have:

  • Trouble feeding
  • Low muscle tone
  • Seizures
  • Abnormal head size
  • Various brain problems
  • Distinct facial features

FH deficiency is different than HLRCC. If 2 people with HLRCC have a child together, there is a 25% (1 in 4) chance for each of their children to have FH deficiency.

Diagnosis of HLRCC

Health history

A health care provider may suspect that your child has HLRCC after studying their medical and family cancer history.

This information helps the health care provider and the genetic counselor know if:

  • There are more cancers than normal in your family
  • These cancers happened at a younger age than expected
  • The cancers are those that are seen in HLRCC

Your provider or genetics counselor may recommend FH genetic testing if they suspect HLRCC . Learn more about types of genetic tests.

Genetic testing for HLRCC

A blood sample is sent to a genetic testing lab. The lab runs genetic tests that looks for changes in the FH gene.

If your child has an FH mutation, the genetic counselor will work with your family to:

  • Find out if other family members should consider testing for an FH mutation
  • Help your family understand the increased cancer risks with HLRCC
  • Give you information to help with your decisions about prenatal genetic testing

Genetic testing before or during pregnancy

Parents may choose to do prenatal testing to find out if a pregnancy is affected with a known FH mutation. Testing may take place either before pregnancy occurs or during pregnancy.

You should work with a genetic counselor to review the pros and cons of the test. The genetic counselor can also help you prepare for the test results.

Testing before pregnancy is called preimplantation genetic testing (PGT). This special type of genetic testing is done along with in vitro fertilization (IVF). PGT tests embryos for a known FH mutation before a provider places the embryo into the uterus.

Testing during pregnancy can help providers see if a pregnancy has a known FH mutation. A doctor gathers cells from the pregnancy in 1 of 2 ways:

  • Chorionic villus sampling (CVS) is done during the first 3 months of pregnancy (1st trimester).
  • Amniocentesis is done after the first 3 months of pregnancy (2nd trimester or later).

After tissue collection, the lab checks the sample for the FH mutation. Both tests carry minor risks. Discuss risks with an experienced health care provider or a genetic counselor.

Special concerns for genetic testing

Take time to think carefully about the benefits and risks of genetic testing. Speak with a genetic counselor before testing. If you decide to get tested, talk with your health care provider or a genetic counselor about your results so you can understand what they mean.

Sometimes, children or adults with HLRCC feel sad, anxious, or angry after getting their test results. Parents may feel guilty if they pass the FH gene mutation to 1 or more of their children. People with a FH gene mutation may also have trouble getting disability or life insurance.

Read more about genetic discrimination.

Monitoring and follow-up care for HLRCC

People with HLRCC need regular screenings to detect cancer as early as possible. They should have a provider who knows the condition well. The goal of screening is to find and treat tumors early to allow for the best outcome.

Cancer screening for those with HLRCC
Recommended screening for patients with HLRCC include:

  • Yearly physical exams by a health care provider who is familiar with the condition
  • Yearly skin exams beginning at diagnosis to look for leiomyomas and signs of leiomyosarcoma
  • Yearly pelvic exams and pelvic MRI or transvagin*l ultrasound (women): Beginning at 20 years old or at first gynecologic exam (whichever happens first) to look for fibroids and rare signs of leiomyosarcoma
  • Yearly kidney MRI beginning at 8 years old to look for kidney tumors

There are no uniform guidelines to look for signs of pheochromocytomas or paragangliomas. But patients with a family history or specific FH mutations related to nerve cell tumors and adrenal gland hormone-secreting tumors may have these tests:

  • Baseline blood pressure
  • Baseline MRI from skull base through pelvis
  • Plasma fractionated metanephrines

Living with HLRCC

Children with HLRCC are at risk of developing tumors during their lifetimes. They should monitor their health and adopt healthful habits throughout life. It is important to have regular physical checkups and screenings. That way, any tumor can be found early at the most treatable stage.

Problems to watch for

People with HLRCC should watch closely for general signs or symptoms that could signal tumors, including:

  • Aches, pains, lumps, or swelling that cannot be explained
  • Pain in the abdomen (belly) or the pelvis
  • Blood in the urine
  • In women: heavy menstrual bleeding or irregular menstrual cycles

Maintain a healthy lifestyle

Habits that will help you maintain a healthy lifestyle include:

  • Eat a healthy diet with lots of fruit and vegetables.
  • Get regular exercise.
  • Avoid excess sun exposure. Always wear a hat, protective clothing, and sunscreen (SPF 30 or higher) when out in the sun.
  • Avoid smoking or the use of tobacco products.
  • Avoid being around secondhand smoke.
  • Avoid excessive alcohol use.

HLRCC care at St. Jude

TheSt. Jude Cancer Predisposition Programis dedicated to diagnosing and screening children with a genetic predisposition for cancer. Our program offers the best clinical care possible. We engage in cutting-edge research to gain more information about genetic disorders and cancer, and to improve care and treatment for patients who are affected by these conditions.Learn more about theDivision of Cancer Predisposition at St. Jude.

Our genetic counselors, clinicians, genetics nurse practitioners, and research assistants work together to provide patients with:

  • A complete health history
  • A record of cancer that happened over the past 3 generations (family tree or pedigree) to see how diseases were passed down
  • Physical exams to check for genetic disease
  • Confidential genetic counseling and testing
  • Cancer screenings for those with genetic disease to detect and treat cancer as soon as it occurs
  • Recommended cancer treatments and ways to reduce cancer risk
  • Genetic testing for immediate (1st degree) relatives

DICER1 syndrome increases your child’s risk for many types of cancer.

Related clinical trials

St. Jude offers clinical trials and cancer research studies for children, teens, and young adults who have cancers linked to HLRCC. See diseases treated at St. Jude.

Learn more about clinical research at St. Jude.

Recruiting

GENETX: Assessing Gene Therapy Communication Needs

Study goal:

To learn more about participants beliefs, attitudes, and questions about gene therapy to help make web-based resources to share information. This could help patients make treatment decisions.

Diagnosis:

Neurological disorders, sickle cell disease, hemophilia, inherited genetic diseases

Age:

18 to 35 years old with rare genetic diseases

Recruiting

Published results

G4K: Genomes for Kids

Study goal:

The main goal of this study is to learn more about the reasons childhood tumors form and how to treat them better.

Diagnosis:

Leukemia, lymphoma, genetics and genomics, solid tumor

Recruiting

TBANK: Collecting, Banking, and Distributing Human Tissue Samples in St. Jude Biorepository

Study goal:

To provide a high-quality repository of tumor and normal samples to facilitate translational research performed by St Jude faculty and their collaborators

Diagnosis:

All diseases

Recruiting

PG4KDS: Clinical Implementation of Pharmacogenetics

Study goal:

1) Test each patient for hundreds of gene variations that might be important for drug use. All of the gene test results will be in the research laboratory, but as time goes on, the study will evaluate scientific evidence and selectively move test results for a few genes into the medical record if the evidence strongly shows that the result can help in better prescribing of drugs for patients; 2) Estimate how often pharmacogenetic test results are moved from research tests into a patient’s medical record; 3) Use methods to choose which of these tests should be put in the medical record; 4) Use computer-based tools in the electronic medical record to help doctors use gene test results when prescribing drugs; 5) Share feelings and concerns of patients and their families about gene test information being put in their medical record.

Recruiting

SJFAMILY: Study of Cancer in Families

Study goal:

The main purpose of this trial is to learn about the genetic causes of cancer.

Diagnosis:

Solid tumors, brain tumors, leukemia

Age:

Younger than 50 years old

Hereditary Leiomyomatosis and Renal Cell Carcinoma (1)

Seeking treatment at St. Jude

Patients accepted to St. Jude must have a disease we treat and must be referred by a physician or other qualified medical professional. We accept most patients based on their ability to enroll in an open clinical trial.

How to seek treatment

Contact the Physician / Patient Referral Office

Submit online referral form

Call: 1-888-226-4343 (toll-free) or 901-595-4055 (local) |Fax: 901-595-4011 |Email: referralinfo@stjude.org|24-hour pager: 1-800-349-4334

Learn more

If you have questions about the Genetic Predisposition Clinic and care for HLRCC, email our team at GPTeam@stjude.org.

  • Diseases Treated at St. Jude
  • Genetic Predisposition Syndromes
  • Genetic Disorders
  • Cancer Predisposition Program
  • Genetic Discrimination
  • Inherited Risk and Genetic Testing

Resources outside of St. Jude

Hereditary Leiomyomatosis and Renal Cell Carcinoma (2024)
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