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Hereditary leiomyomatosis and renal cell cancer(MCL; MCUL1; HLRCC; LRCC)

MedGen UID:
353771
Concept ID:
C1708350
Neoplastic Process
Synonyms: Cutaneous leiomyomata with uterine leiomyomata; Familial leiomyomatosis; Leiomyoma, hereditary multiple, of skin; Leiomyoma, multiple cutaneous; Multiple cutaneous and uterine leiomyomata; MULTIPLE CUTANEOUS AND UTERINE LEIOMYOMATA 1, WITH OR WITHOUT RENAL CELL CARCINOMA; Multiple cutaneous and uterine leiomyomatosis; Multiple cutaneous leiomyomas; Reed syndrome
SNOMED CT: HLRCC - hereditary leiomyomatosis and renal cell cancer (1162799008); Familial leiomyomatosis with renal carcinoma (1162799008); Hereditary leiomyomatosis with renal carcinoma (1162799008); Familial leiomyomatosis and renal cell cancer (1162799008); Hereditary leiomyomatosis and renal cell carcinoma (1162799008); Hereditary leiomyomatosis and renal cell cancer (1162799008)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): FH (1q43)
 
HPO: HP:0007437
Monarch Initiative: MONDO:0007888
OMIM®: 150800
Orphanet: ORPHA523

Disease characteristics

Excerpted from the GeneReview: FH Tumor Predisposition Syndrome
FH tumor predisposition syndrome is characterized by cutaneous leiomyomata, uterine leiomyomata (fibroids), and/or renal tumors. Pheochromocytoma and paraganglioma have also been described in a small number of families. Cutaneous leiomyomata appear as skin-colored to light brown papules or nodules distributed over the trunk and extremities, and occasionally on the face, and appear at a mean age of 30 years, increasing in size and number with age. Uterine leiomyomata tend to be numerous and large; age at diagnosis ranges from 18 to 53 years, with most women experiencing irregular or heavy menstruation and pelvic pain. Renal tumors are usually unilateral, solitary, and aggressive. They are associated with poor survival due to clinical aggressiveness and propensity to metastasize despite small primary tumor size. The median age of detection is approximately age 40 years. [from GeneReviews]
Authors:
Junne Kamihara  |  Kris Ann Schultz  |  Huma Q Rana   view full author information

Additional descriptions

From OMIM
Hereditary leiomyomatosis and renal cell cancer is an autosomal dominant tumor predisposition syndrome characterized by the variable development of 3 tumors: cutaneous piloleiomyomata that develop in essentially all patients by age 40 years; leiomyomata (fibroids) of the uterus, and rarely leiomyosarcomas, at a mean age of 30 years (range, 18 to 52 years); and type 2 papillary renal cell carcinoma at a mean age of 46 years (range, 17 to 75 years), which occurs in about 20% of patients. Type 2 papillary renal cell carcinoma is a pathologic subtype characterized by large tumor cells with eosinophilic cytoplasm and pseudostratified nuclei; it shows an aggressive clinical course. Some patients with FH mutations may develop collecting duct renal cell carcinoma. The main focus of management in HLRCC is prevention of disease and death due to renal cancer (summary by Gardie et al., 2011; Smit et al., 2011; and Lehtonen, 2011). For a general discussion of papillary renal cell carcinoma, see RCCP1 (605074).  http://www.omim.org/entry/150800
From MedlinePlus Genetics
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. People with HLRCC are commonly diagnosed with kidney cancer 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).  https://medlineplus.gov/genetics/condition/hereditary-leiomyomatosis-and-renal-cell-cancer

Clinical features

From HPO
Renal cell carcinoma
MedGen UID:
766
Concept ID:
C0007134
Neoplastic Process
A type of carcinoma of the kidney with origin in the epithelium of the proximal convoluted renal tubule.
Uterine leiomyoma
MedGen UID:
21801
Concept ID:
C0042133
Neoplastic Process
Uterine leiomyoma (UL), commonly known as fibroids, are benign tumors of the uterine myometrium. They represent the most prevalent pelvic tumors in women and are found in more than 75% of women of reproductive age. Approximately 20 to 25% of women with UL exhibit symptoms including menorrhagia, infertility, pelvic pain, and a range of complications during pregnancy. UL are the leading cause for hysterectomy in the United States, accounting for 30% of all hysterectomies (summary by Eggert et al., 2012).
Uterine leiomyosarcoma
MedGen UID:
83679
Concept ID:
C0280631
Neoplastic Process
The presence of a leiomyosarcoma of the uterus.
Cutaneous leiomyoma
MedGen UID:
87533
Concept ID:
C0346064
Neoplastic Process
The presence of leiomyoma of the skin.
Cutaneous leiomyosarcoma
MedGen UID:
87534
Concept ID:
C0346067
Neoplastic Process
The presence of leiomyosarcoma of the skin.
Hereditary leiomyomatosis and renal cell cancer
MedGen UID:
353771
Concept ID:
C1708350
Neoplastic Process
FH tumor predisposition syndrome is characterized by cutaneous leiomyomata, uterine leiomyomata (fibroids), and/or renal tumors. Pheochromocytoma and paraganglioma have also been described in a small number of families. Cutaneous leiomyomata appear as skin-colored to light brown papules or nodules distributed over the trunk and extremities, and occasionally on the face, and appear at a mean age of 30 years, increasing in size and number with age. Uterine leiomyomata tend to be numerous and large; age at diagnosis ranges from 18 to 53 years, with most women experiencing irregular or heavy menstruation and pelvic pain. Renal tumors are usually unilateral, solitary, and aggressive. They are associated with poor survival due to clinical aggressiveness and propensity to metastasize despite small primary tumor size. The median age of detection is approximately age 40 years.
Decreased fumarate hydratase activity
MedGen UID:
343007
Concept ID:
C1853903
Finding
An abnormality of Krebs cycle metabolism that is characterized by a decreased rate of fumarate hydratase activity.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary leiomyomatosis and renal cell cancer

Conditions with this feature

Hereditary leiomyomatosis and renal cell cancer
MedGen UID:
353771
Concept ID:
C1708350
Neoplastic Process
FH tumor predisposition syndrome is characterized by cutaneous leiomyomata, uterine leiomyomata (fibroids), and/or renal tumors. Pheochromocytoma and paraganglioma have also been described in a small number of families. Cutaneous leiomyomata appear as skin-colored to light brown papules or nodules distributed over the trunk and extremities, and occasionally on the face, and appear at a mean age of 30 years, increasing in size and number with age. Uterine leiomyomata tend to be numerous and large; age at diagnosis ranges from 18 to 53 years, with most women experiencing irregular or heavy menstruation and pelvic pain. Renal tumors are usually unilateral, solitary, and aggressive. They are associated with poor survival due to clinical aggressiveness and propensity to metastasize despite small primary tumor size. The median age of detection is approximately age 40 years.

Professional guidelines

PubMed

Singh S, Chaurasia A, Gopal N, Malayeri A, Ball MW
Discov Med 2022 Nov-Dec;34(173):205-220. PMID: 36602871
Uyar B, Acar EM, Subaşıoğlu A
Dermatol Ther 2020 Mar;33(2):e13226. Epub 2020 Jan 19 doi: 10.1111/dth.13226. PMID: 31917494
Andrici J, Gill AJ, Hornick JL
Semin Diagn Pathol 2018 May;35(3):161-169. Epub 2017 Jun 27 doi: 10.1053/j.semdp.2017.05.004. PMID: 28662997

Recent clinical studies

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Cesk Patol 2021 Summer;57(2):96-104. PMID: 34275319
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World J Urol 2018 Dec;36(12):1891-1898. Epub 2018 Apr 21 doi: 10.1007/s00345-018-2288-5. PMID: 29680948Free PMC Article
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Adv Chronic Kidney Dis 2014 Jan;21(1):81-90. doi: 10.1053/j.ackd.2013.10.001. PMID: 24359990Free PMC Article

Diagnosis

Wilde BR, Chakraborty N, Matulionis N, Hernandez S, Ueno D, Gee ME, Esplin ED, Ouyang K, Nykamp K, Shuch B, Christofk HR
Cancer Discov 2023 Sep 6;13(9):2072-2089. doi: 10.1158/2159-8290.CD-22-0874. PMID: 37255402Free PMC Article
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Therapy

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Prognosis

Andrici J, Gill AJ, Hornick JL
Semin Diagn Pathol 2018 May;35(3):161-169. Epub 2017 Jun 27 doi: 10.1053/j.semdp.2017.05.004. PMID: 28662997
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Fam Cancer 2014 Dec;13(4):637-44. doi: 10.1007/s10689-014-9735-2. PMID: 25012257Free PMC Article

Clinical prediction guides

Seo JY, Ahn JY, Keam B, Kim M, Yoon S, Lee JL, Park K, Park I
Ann Lab Med 2021 Mar 1;41(2):207-213. doi: 10.3343/alm.2021.41.2.207. PMID: 33063682Free PMC Article
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Kuroda N, Ohe C, Kato I, Furuya M, Baba M, Nagashima Y, Nakatani Y, Murakami I, Zhou M, Michal M, He O, Amin MB
Pol J Pathol 2017;68(4):284-290. doi: 10.5114/pjp.2017.73920. PMID: 29517197
Menko FH, Maher ER, Schmidt LS, Middelton LA, Aittomäki K, Tomlinson I, Richard S, Linehan WM
Fam Cancer 2014 Dec;13(4):637-44. doi: 10.1007/s10689-014-9735-2. PMID: 25012257Free PMC Article
Wong MH, Tan CS, Lee SC, Yong Y, Ooi AS, Ngeow J, Tan MH
Fam Cancer 2014 Jun;13(2):281-9. doi: 10.1007/s10689-014-9703-x. PMID: 24526232

Recent systematic reviews

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Eur Urol 2019 Dec;76(6):754-764. Epub 2019 Jul 18 doi: 10.1016/j.eururo.2019.06.015. PMID: 31326218Free PMC Article

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