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Genetics Home Reference: your guide to understanding genetic conditions
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Hereditary leiomyomatosis and renal cell cancer

(often shortened to HLRCC)
Reviewed April 2008

What is HLRCC?

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a disorder in which affected individuals tend to develop benign tumors containing smooth muscle tissue (leiomyomas) in the skin and, in females, the uterus. This condition also increases the risk of kidney cancer.

In this disorder, growths on the skin (cutaneous leiomyomas) typically develop in the third decade of life. Most of these growths arise from the tiny muscles around the hair follicles that cause "goosebumps". They appear as bumps or nodules on the trunk, arms, legs, and occasionally on the face. Cutaneous leiomyomas may be the same color as the surrounding skin, or they may be darker. Some affected individuals have no cutaneous leiomyomas or only a few, but the growths tend to increase in size and number over time. Cutaneous leiomyomas are often more sensitive than the surrounding skin to cold or light touch, and may be painful.

Most women with HLRCC also develop uterine leiomyomas (fibroids). While uterine fibroids are very common in the general population, women with HLRCC tend to have numerous large fibroids that appear earlier than in the general population.

Approximately 10 percent to 16 percent of people with HLRCC develop a type of kidney cancer called renal cell cancer. The signs and symptoms of renal cell cancer may include lower back pain, blood in the urine, or a mass in the kidney that can be felt upon physical examination. Some people with renal cell cancer have no symptoms until the disease is advanced. The average age at which people with HLRCC are diagnosed with kidney cancer is in their forties.

This disorder, especially if it appears in individuals or families without renal cell cancer, is also sometimes called multiple cutaneous leiomyomatosis (MCL) or multiple cutaneous and uterine leiomyomatosis (MCUL).

How common is HLRCC?

HLRCC has been reported in approximately 100 families worldwide. Its prevalence is unknown.

What genes are related to HLRCC?

Mutations in the FH gene cause hereditary leiomyomatosis and renal cell cancer. The FH gene provides instructions for making an enzyme called fumarase (also known as fumarate hydratase). This enzyme participates in an important series of reactions known as the citric acid cycle or Krebs cycle, which allows cells to use oxygen and generate energy. Specifically, fumarase helps convert a molecule called fumarate to a molecule called malate.

People with HLRCC are born with one mutated copy of the FH gene in each cell. The second copy of the FH gene in certain cells may also acquire mutations as a result of environmental factors such as ultraviolet radiation from the sun or a mistake that occurs as DNA copies itself during cell division.

FH gene mutations may interfere with the enzyme's role in the citric acid cycle, resulting in a buildup of fumarate. Researchers believe that the excess fumarate may interfere with the regulation of oxygen levels in the cell. Chronic oxygen deficiency (hypoxia) in cells with two mutated copies of the FH gene may encourage tumor formation and result in the tendency to develop leiomyomas and renal cell cancer.

Related Gene(s)

Changes in this gene are associated with hereditary leiomyomatosis and renal cell cancer.

  • FH

How do people inherit HLRCC?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of HLRCC?

These resources address the diagnosis or management of HLRCC and may include treatment providers.

  • Gene Review: Hereditary Leiomyomatosis and Renal Cell Cancer (http://www.ncbi.nlm.nih.gov/books/NBK1252)
  • Genetic Testing Registry: Hereditary leiomyomatosis and renal cell cancer (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1708350)
  • MedlinePlus Encyclopedia: Renal Cell Carcinoma (http://www.nlm.nih.gov/medlineplus/ency/article/000516.htm)

You might also find information on the diagnosis or management of HLRCC in Educational resources (http://www.ghr.nlm.nih.gov/condition/hereditary-leiomyomatosis-and-renal-cell-cancer/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/hereditary-leiomyomatosis-and-renal-cell-cancer/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about HLRCC?

You may find the following resources about HLRCC helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for HLRCC?

  • hereditary leiomyomatosis and renal cell carcinoma
  • leiomyomatosis and renal cell cancer
  • LRCC
  • MCL
  • MCUL
  • multiple cutaneous and uterine leiomyomata
  • multiple cutaneous leiomyoma
  • Reed's syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about HLRCC?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding HLRCC?

autosomal ; autosomal dominant ; benign ; cancer ; carcinoma ; cell ; cell division ; chronic ; cutaneous ; deficiency ; DNA ; enzyme ; gene ; hereditary ; hypoxia ; inherited ; kidney ; molecule ; mutation ; oxygen ; oxygen deficiency ; population ; prevalence ; radiation ; renal ; syndrome ; tissue ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Alam NA, Rowan AJ, Wortham NC, Pollard PJ, Mitchell M, Tyrer JP, Barclay E, Calonje E, Manek S, Adams SJ, Bowers PW, Burrows NP, Charles-Holmes R, Cook LJ, Daly BM, Ford GP, Fuller LC, Hadfield-Jones SE, Hardwick N, Highet AS, Keefe M, MacDonald-Hull SP, Potts ED, Crone M, Wilkinson S, Camacho-Martinez F, Jablonska S, Ratnavel R, MacDonald A, Mann RJ, Grice K, Guillet G, Lewis-Jones MS, McGrath H, Seukeran DC, Morrison PJ, Fleming S, Rahman S, Kelsell D, Leigh I, Olpin S, Tomlinson IP. Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency. Hum Mol Genet. 2003 Jun 1;12(11):1241-52. (http://www.ncbi.nlm.nih.gov/pubmed/12761039?dopt=Abstract)
  • Badeloe S, van Geel M, van Steensel MA, Bastida J, Ferrando J, Steijlen PM, Frank J, Poblete-Gutiérrez P. Diffuse and segmental variants of cutaneous leiomyomatosis: novel mutations in the fumarate hydratase gene and review of the literature. Exp Dermatol. 2006 Sep;15(9):735-41. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16881969?dopt=Abstract)
  • Grubb RL 3rd, Franks ME, Toro J, Middelton L, Choyke L, Fowler S, Torres-Cabala C, Glenn GM, Choyke P, Merino MJ, Zbar B, Pinto PA, Srinivasan R, Coleman JA, Linehan WM. Hereditary leiomyomatosis and renal cell cancer: a syndrome associated with an aggressive form of inherited renal cancer. J Urol. 2007 Jun;177(6):2074-9; discussion 2079-80. (http://www.ncbi.nlm.nih.gov/pubmed/17509289?dopt=Abstract)
  • King A, Selak MA, Gottlieb E. Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene. 2006 Aug 7;25(34):4675-82. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16892081?dopt=Abstract)
  • Lehtonen HJ, Kiuru M, Ylisaukko-Oja SK, Salovaara R, Herva R, Koivisto PA, Vierimaa O, Aittomäki K, Pukkala E, Launonen V, Aaltonen LA. Increased risk of cancer in patients with fumarate hydratase germline mutation. J Med Genet. 2006 Jun;43(6):523-6. Epub 2005 Sep 9. (http://www.ncbi.nlm.nih.gov/pubmed/16155190?dopt=Abstract)
  • Lorenzato A, Olivero M, Perro M, Brière JJ, Rustin P, Di Renzo MF. A cancer-predisposing "hot spot" mutation of the fumarase gene creates a dominant negative protein. Int J Cancer. 2008 Feb 15;122(4):947-51. (http://www.ncbi.nlm.nih.gov/pubmed/17960613?dopt=Abstract)
  • Ratcliffe PJ. Fumarate hydratase deficiency and cancer: activation of hypoxia signaling? Cancer Cell. 2007 Apr;11(4):303-5. (http://www.ncbi.nlm.nih.gov/pubmed/17418405?dopt=Abstract)
  • Sudarshan S, Linehan WM, Neckers L. HIF and fumarate hydratase in renal cancer. Br J Cancer. 2007 Feb 12;96(3):403-7. Epub 2007 Jan 9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17211469?dopt=Abstract)
  • Sudarshan S, Pinto PA, Neckers L, Linehan WM. Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer--a distinct form of hereditary kidney cancer. Nat Clin Pract Urol. 2007 Feb;4(2):104-10. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17287871?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2008
Published: November 17, 2014