Hereditary leiomyomatosis and renal cell cancer

Información en español Title

Other Names:

LRCC; HLRCC; Familial leiomyomatosis; LRCC; HLRCC; Familial leiomyomatosis; Multiple cutaneous and uterine leiomyomata; MCUL; Reed's syndrome; Multiple cutaneous leiomyomata; MCL See More

Categories:

Congenital and Genetic Diseases; Kidney and Urinary Diseases; Rare Cancers; Congenital and Genetic Diseases; Kidney and Urinary Diseases; Rare Cancers; Skin Diseases See More

Summary Summary

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a condition that causes benign tumors of smooth muscle tissue in the skin (cutaneous leiomyomas) and in the uterus in females (uterine leiomyomas, or fibroids). The condition also increases the risk of kidney cancer. Signs and symptoms usually begin in adulthood as skin growths appear on the torso, arms, legs, and occasionally on the face. They tend to increase in size and number over time. About 10% to 16% of people with HLRCC develop a type of kidney cancer called renal cell cancer; symptoms of this cancer may include lower back pain, blood in the urine, and/or a mass in the kidney that can be felt by a physician. Some people have no symptoms until the cancer is advanced. HLRCC is caused by mutations in the FH gene and is inherited in an autosomal dominant manner.^[1]

Last updated: 1/9/2014

Symptoms Symptoms

Signs and symptoms of hereditary leiomyomatosis and renal cell cancer (HLRCC) typically begin in adulthood at an average age of 25. The skin growths (cutaneous leiomyomata) appear as skin-colored or light brown bumps on the torso and extremities, and occasionally on the face. They usually increase in size and number with age. They may be more sensitive than the surrounding skin and be painful. Uterine leiomyomata (fibroids) also occur in almost all affected women and tend to be large and numerous. Most women with these have irregular or heavy periods and pelvic pain. A renal tumor occurs in about 10% to 16% of affected individuals (at an average age of 44 years) and may cause blood in the urine, lower back pain, and a palpable mass. Some people with renal cell cancer have no symptoms until the cancer is advanced.^[2]^[3]

Last updated: 1/9/2014

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormality of the musculature	Muscular abnormality	0003011
Cutaneous leiomyoma		0007620
Multiple cutaneous leiomyomas		0007437
30%-79% of people have these symptoms
Pruritus	Itching Itchy skin Skin itching [ more ]	0000989
5%-29% of people have these symptoms
Barrett esophagus		0100580
Cataract	Clouding of the lens of the eye Cloudy lens [ more ]	0000518
Cutaneous leiomyosarcoma		0006755
Papillary renal cell carcinoma type 2		0006732
Uterine leiomyoma		0000131
Uterine leiomyosarcoma		0002891
Vaginal neoplasm	Vaginal tumor	0100650
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance		0000006
Decreased fumarate hydratase activity		0003536
Incomplete penetrance		0003829
Renal cell carcinoma	Cancer starting in small tubes in kidneys	0005584

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 3/1/2020

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by changes (mutations) in the FH gene. This gene gives the body instructions for making an enzyme called fumarase which is needed for a series of reactions that lets cells use oxygen and energy (the citric acid cycle, or Krebs cycle). People with HLRCC are born with one mutated copy of the FH gene in each cell. The second copy of the gene in some cells can mutate later on from factors in the environment, such as radiation from the sun or an error during cell division. A mutation can interfere with fumarase's role in the citric acid cycle, which may affect the regulation of oxygen levels in cells. Long-term oxygen deficiency in cells with two mutated copies of the FH gene may contribute to tumors growth and the tendency to develop leiomyomas and/or renal cell cancer.^[2]

Last updated: 1/9/2014

Inheritance Inheritance

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is inherited in an autosomal dominant pattern, which means that having one mutated copy of the gene in each cell is enough to cause symptoms of the condition. In some cases, an affected person inherits the mutated copy of the gene from an affected parent. Other cases result from new mutations in the gene and that occur for the first time in in the affected individual.^[2]

When an individual with an autosomal dominant condition has children, each child has a 50% (1 in 2) risk to inherit the mutated gene. This is the case regardless of which parent has the condition.

Last updated: 1/9/2014

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment Treatment

Skin growths (cutaneous leiomyomas) associated with hereditary leiomyomatosis and renal cell cancer (HLRCC) should be examined by a dermatologist. Treatment of these may include surgery to remove a painful growth; cryoablation and/or lasers; and/or medications such as calcium channel blockers, alpha blockers, nitroglycerin, antidepressants, and/or antiepileptic drugs (AEDs), which have been reported to reduce pain.^[4] Uterine fibroids should be evaluated by a gynecologist. These are typically treated in the same manner as those that occur in the general population. However, most women with HLRCC need medication and/or surgical removal of the fibroids (myomectomy) at a younger age. Medications may include gonadotropin-releasing hormone agonists (GnRHa), antihormonal drugs, and pain relievers. Hysterectomy should be performed only when necessary.^[4] Early detection of kidney tumors in HLRCC is important because they grow aggressively. Total nephrectomy may be strongly considered in individuals with a detectable renal mass.^[4]

Last updated: 1/9/2014

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Sorafenib (Brand name: Nexavar) - Manufactured by Bayer Pharmaceutical Corporation
FDA-approved indication: Treatment of patients with advanced renal cell carcinoma.
National Library of Medicine Drug Information Portal
Medline Plus Health Information
Aldesleukin (Brand name: Proleukin®) - Manufactured by Chiron Corporation
FDA-approved indication: Treatment of adults (>18 years old) with metastatic renal cell carcinoma.
National Library of Medicine Drug Information Portal
Medline Plus Health Information
Temsirolimus (Brand name: Torisel®) - Manufactured by Wyeth Pharmaceuticals, Inc.
FDA-approved indication: Treatment of advanced renal cell carcinoma
National Library of Medicine Drug Information Portal
Medline Plus Health Information

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include familial renal cancer syndromes such as Von Hippel-Lindau syndrome, Birt-Hogg-Dubé syndrome and hereditary papillary renal cancer (see these terms), as well as uterine fibroids and cutaneous lesions. Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Hereditary leiomyomatosis and renal cell cancer. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.

Patient Registry

A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Hereditary leiomyomatosis and renal cell cancer. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

Registries for Hereditary leiomyomatosis and renal cell cancer:
MyVHL: Patient Natural History Study

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Family Alliance
c/o VHL Family Alliance
1208 VFW Parkway, Suite 303
Boston, MA 02132
Toll-free: 800-767-4845 ext. 3
Telephone: 617-277-5667 ext. 3
E-mail: hlrcc@vhl.org
Website: http://www.hlrccinfo.org/
National Uterine Fibroids Foundation
P.O. Box 9688
Colorado Springs, CO 80932-0688
Toll-free: 800-874-7247
Telephone: 719-633-3454
E-mail: info@NUFF.org
Website: http://www.nuff.org

Social Networking Websites

RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

Organizations Providing General Support

American Kidney Fund, Inc.
6110 Executive Boulevard
Suite 1010
Rockville, MD 20852
Toll-free: 866-300-2900
Telephone: 301-881-3052
E-mail: helpline@kidneyfund.org
Website: http://www.kidneyfund.org
National Kidney Foundation
30 East 33rd Street
New York, NY 10016
Toll-free: 800-622-9010
Telephone: 212-889-2210
Fax: 212-689-9261
E-mail: info@kidney.org
Website: https://www.kidney.org/
The Kidney Foundation of Canada
700-15 Gervais Drive
Toronto Ontario M3C 1Y8
Canada
Toll-free: 800-387-4474
Telephone: 416-445-0373
Fax: 416-445-7440
E-mail: kidney@kidney.on.ca
Website: http://www.kidney.on.ca

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Cancer.net provides oncologist-approved cancer information from the American Society of Clinical Oncology and has information about Hereditary leiomyomatosis and renal cell cancer.
Genetics Home Reference (GHR) contains information on Hereditary leiomyomatosis and renal cell cancer. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Medscape Reference has a page on leiomyoma that includes some information on hereditary leiomyomatosis and renal cell cancer. You may need to register to view this medical reference page, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
The Online Mendelian Inheritance in Man (OMIM)
The Online Mendelian Inheritance in Man (OMIM)
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Hereditary leiomyomatosis and renal cell cancer. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

Pithukpakorn M, Toro J. Hereditary leiomyomatosis and renal cell cancer. GeneReviews. 2006; http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hlrcc#hlrcc.References. Accessed 7/31/2009.
Hereditary leiomyomatosis and renal cell cancer. Genetics Home Reference. April 2008; http://ghr.nlm.nih.gov/condition=hereditaryleiomyomatosisandrenalcellcancer. Accessed 6/30/2009.
Manop Pithukpakorn and Jorge R Toro. Hereditary Leiomyomatosis and Renal Cell Cancer. GeneReviews. November 2, 2010; http://www.ncbi.nlm.nih.gov/books/NBK1252/. Accessed 1/9/2014.
Pithukpakorn M, Toro JR. Hereditary Leiomyomatosis and Renal Cell Cancer. GeneReviews. August 6, 2015; http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hlrcc. Accessed 11/17/2015.