Hereditary leiomyomatosis and renal cell cancer

A hereditary condition where patients present with cutaneous LEIOMYOMAS (female patients may also have uterine leiomyomas) and are at increased risk for developing KIDNEY NEOPLASMS. Tumors initally appear during adulthood on the skin of the torso, arms, legs, and face and increase in size and number over time; 10% to 16% of patients develop RENAL CELL CARCINOMA. A heterozygous germline mutation in the FH gene has been identified. OMIM: 150800

Also Known As:

Cutaneous leiomyomata with uterine leiomyomata; Leiomyoma, hereditary multiple, of skin; Leiomyoma, multiple cutaneous; Leiomyomatosis and renal cell cancer, hereditary; Multiple cutaneous and uterine leiomyomata 1; Multiple cutaneous and uterine leiomyomatosis; Reed's syndrome

Networked: 131 relevant articles (2 outcomes, 3 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Hereditary leiomyomatosis and renal cell cancer
2.	Neoplasms (Cancer)
3.	Birt-Hogg-Dube Syndrome
4.	Tuberous Sclerosis (Bourneville's Disease)
5.	von Hippel-Lindau Disease (von Hippel Lindau Disease)

Experts

1.	Aaltonen, Lauri A: 14 articles (01/2022 - 04/2005)
2.	Launonen, Virpi: 8 articles (09/2011 - 04/2005)
3.	Kiuru, Maija: 8 articles (06/2010 - 04/2005)
4.	Linehan, W Marston: 7 articles (12/2016 - 07/2003)
5.	Pollard, Patrick J: 7 articles (08/2014 - 01/2006)
6.	Vahteristo, Pia: 6 articles (01/2022 - 07/2009)
7.	Adam, Julie: 6 articles (12/2016 - 10/2010)
8.	Lehtonen, Heli J: 6 articles (09/2011 - 01/2006)
9.	Ooi, Aikseng: 5 articles (01/2022 - 09/2012)
10.	Lehtonen, Rainer: 5 articles (06/2010 - 04/2005)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Hereditary leiomyomatosis and renal cell cancer:

1.	Fumarate Hydratase (Fumarase)IBA 01/01/2014 - "Genetic studies on human patients have shown that polymorphisms in the fumarase gene are responsible for diseases such as hereditary leiomyomatosis and renal cell cancer. " 11/03/2023 - "Cryptic splice mutation in the fumarate hydratase gene in patients with clinical manifestations of Hereditary Leiomyomatosis and Renal Cell Cancer." 01/01/2023 - "A Missense Mutation c.1132G > A in Fumarate Hydratase (FH) Leads to Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Syndrome and Insights into Clinical Management in Uterine Leiomyomata." 03/01/2022 - "Rare variant in the fumarate hydratase gene found in patients with clinical features of hereditary leiomyomatosis and renal cell cancer (HLRCC): A case series." 11/01/2021 - "Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome caused by heterozygous pathogenic germline variants in the fumarate hydratase (FH) gene. "
2.	Reactive Oxygen Species (Oxygen Radicals)IBA 03/01/2009 - "Here, we report that hereditary leiomyomatosis and renal cell cancer tumors indeed overexpress LDH-A, that LDH-A inhibition results in increased apoptosis in a cell with FH deficiency and that this effect is reactive oxygen species mediated, and that LDH-A knockdown in the background of FH knockdown results in significant reduction in tumor growth in a xenograft mouse model."
3.	Lactate Dehydrogenase 5IBA 03/01/2009 - "LDH-A inhibition, a therapeutic strategy for treatment of hereditary leiomyomatosis and renal cell cancer." 03/01/2009 - "Here, we report that hereditary leiomyomatosis and renal cell cancer tumors indeed overexpress LDH-A, that LDH-A inhibition results in increased apoptosis in a cell with FH deficiency and that this effect is reactive oxygen species mediated, and that LDH-A knockdown in the background of FH knockdown results in significant reduction in tumor growth in a xenograft mouse model."
4.	EnzymesIBA 02/01/2007 - "Germline mutations in a gene that encodes a Krebs cycle enzyme have been found to result in a distinct clinical entity referred to as hereditary leiomyomatosis and renal cell cancer (HLRCC). " 01/01/2005 - "The Mendelian tumour syndromes hereditary leiomyomatosis and renal cell cancer (HLRCC) and hereditary paragangliomatosis with phaeochromocytomas (HPGL) result from mutations in nuclear genes (FH and SDHB/C/D, respectively) that encode Krebs cycle enzymes. " 05/15/2014 - "Mutations in FH, resulting in loss of enzyme activity, predispose affected individuals to a rare cancer, hereditary leiomyomatosis and renal cell cancer (HLRCC), characterised by benign smooth muscle cutaneous and uterine tumours (leiomyomata) and an aggressive form of collecting duct and type 2 papillary renal cancer. " 01/01/2016 - "Mutations of the tricarboxylic acid cycle enzyme fumarate hydratase cause hereditary leiomyomatosis and renal cell cancer. " 01/01/2015 - "The hereditary leiomyomatosis and renal cell cancer (HLRCC) association is a rare syndrome caused by mutation of the Kreb's cycle enzyme, fumarate hydratase (FH). "
5.	Succinate Dehydrogenase (Fumarate Reductase)IBA 05/01/2018 - "Specifically, we focus on Carney complex, familial adenomatous polyposis (FAP)-associated cribriform-morular variant of papillary thyroid carcinoma, familial succinate dehydrogenase-related pheochromocytoma/paraganglioma syndromes, hereditary leiomyomatosis and renal cell cancer (HLRCC), medullary thyroid cancer and Multiple Endocrine Neoplasia 2 (MEN2), BAP1 hereditary cancer predisposition syndrome, Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT), and Pancreatic Neuroendocrine Tumor Syndrome (Mahvash disease)." 07/22/2019 - "The present study is a retrospective clinical and morphologic review of 60 hereditary renal tumors from 30 HRCCS patients treated at our institution with either Von Hippel-Lindau disease (VHL), Birt-Hogg-Dubé syndrome (BHD), tuberous sclerosis complex (TSC), hereditary leiomyomatosis and renal cell cancer syndrome, or succinate dehydrogenase (SDH) deficiency syndrome. " 01/01/2023 - "Succinate dehydrogenase (dSDH)-deficient tumors, including pheochromocytoma/paraganglioma, hereditary leiomyomatosis and renal cell cancer-associated renal cell carcinoma (HLRCC-RCC), and gastrointestinal stromal tumors (GIST) without KIT or platelet-derived growth factor receptor alpha mutations are often resistant to cytotoxic chemotherapy, radiotherapy, and many targeted therapies. " 09/15/2007 - "Germline mutations in nuclear genes encoding mitochondrial enzymes fumarate hydratase (FH) and succinate dehydrogenase (subunits SDHB/C/D) have been implicated in the development of tumor syndromes referred to as hereditary leiomyomatosis and renal cell cancer (HLRCC) and hereditary paragangliomatosis (HPGL), respectively. " 11/01/2022 - "A subset of renal tumors (5-8%) are associated with syndromes such as von Hippel-Lindau (VHL) syndrome, Birt-Hogg-Dubé syndrome (BHD), tuberous sclerosis complex (TSC), hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), and BRCA1 associated protein (BAP1) tumor predisposition syndrome, succinate dehydrogenase RCC (SDHB/C/D). "
6.	trans-sodium crocetinate (crocetin)IBA 07/22/2019 - "The present study is a retrospective clinical and morphologic review of 60 hereditary renal tumors from 30 HRCCS patients treated at our institution with either Von Hippel-Lindau disease (VHL), Birt-Hogg-Dubé syndrome (BHD), tuberous sclerosis complex (TSC), hereditary leiomyomatosis and renal cell cancer syndrome, or succinate dehydrogenase (SDH) deficiency syndrome. " 11/01/2022 - "A subset of renal tumors (5-8%) are associated with syndromes such as von Hippel-Lindau (VHL) syndrome, Birt-Hogg-Dubé syndrome (BHD), tuberous sclerosis complex (TSC), hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), and BRCA1 associated protein (BAP1) tumor predisposition syndrome, succinate dehydrogenase RCC (SDHB/C/D). "
7.	FumaratesIBA 01/01/2020 - "Here, we have demonstrated a proof of principle that 1H-MRS can provide a noninvasive diagnosis of hereditary leiomyomatosis and renal cell cancer syndrome or Reed syndrome through detection of fumarate accumulation in vivo. " 01/01/2018 - "Inactivating germline mutations in FH cause hereditary leiomyomatosis and renal cell cancer (HLRCC), a cancer syndrome characterised by accumulation of fumarate. " 01/01/2023 - "Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a cancer syndrome caused by inactivating germline mutations in fumarate hydratase (FH) and subsequent accumulation of fumarate. " 08/29/2014 - "To date, HIF-1α accumulation in hereditary leiomyomatosis and renal cell cancer tumors is thought to result from fumarate-dependent inhibition of prolyl hydroxylases and subsequent evasion from von Hippel-Lindau-dependent degradation. " 04/01/2013 - "In hereditary type 2 papillary renal cell carcinoma (PRCC2, also known as hereditary leiomyomatosis and renal cell cancer), NRF2 activation is a direct consequence of the accumulation of intracellular fumarate, a result of fumarate hydratase (FH) inactivation, but it is not clear how NRF2 may be activated in sporadic forms of PRCC2. "
8.	Proteins (Proteins, Gene)FDA Link 11/08/2012 - "Protein profiling of blood samples from patients with hereditary leiomyomatosis and renal cell cancer by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry." 06/13/2023 - "Deficiency of fumarate hydratase (FH) protein expression in uterine corpus leiomyomas may be attributable to either germline or somatic mutations of the FH gene, the former being definitional for the hereditary leiomyomatosis and renal cell cancer syndrome. " 12/01/2016 - "Loss of Fumarate Hydratase and Aberrant Protein Succination Detected With S-(2-Succino)-Cysteine Staining to Identify Patients With Multiple Cutaneous and Uterine Leiomyomatosis and Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome." 11/01/2022 - "A subset of renal tumors (5-8%) are associated with syndromes such as von Hippel-Lindau (VHL) syndrome, Birt-Hogg-Dubé syndrome (BHD), tuberous sclerosis complex (TSC), hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), and BRCA1 associated protein (BAP1) tumor predisposition syndrome, succinate dehydrogenase RCC (SDHB/C/D). "
9.	Fumaric aciduriaIBA 06/01/2003 - "Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency." 01/01/2022 - "Germline variants in fumarate hydratase (FH) are associated with autosomal dominant (AD) hereditary leiomyomatosis and renal cell cancer (HLRCC) and autosomal recessive (AR) fumarase deficiency (FMRD). " 01/01/2020 - "Mutations of the FH gene have been associated with fumarate hydratase deficiency (FHD), hereditary leiomyomatosis and renal cell cancer (HLRCC), and other diseases. " 01/01/2018 - "Mutations in the FH gene, encoding human fumarase, are associated with fumarate hydratase deficiency (FHD) and hereditary leiomyomatosis and renal cell cancer (HLRCC). "
10.	Tricarboxylic AcidsIBA 01/01/2020 - "Fumarate hydratase (FH) is an enzyme in the tricarboxylic acid (TCA) cycle, biallelic loss-of-function mutations of which are associated with hereditary leiomyomatosis and renal cell cancer. " 01/01/2017 - "Germ line mutations of the gene encoding the tricarboxylic acid (TCA) cycle enzyme fumarate hydratase (FH) cause a hereditary cancer syndrome known as hereditary leiomyomatosis and renal cell cancer (HLRCC). " 01/01/2011 - "Germline mutations of FH, the gene that encodes for the tricarboxylic acid TCA (TCA) cycle enzyme fumarate hydratase, are associated with an inherited form of cancer referred to as Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). "

Therapies and Procedures

1.	Immunotherapy 04/01/2020 - "The preliminary outcome of the combination of immunotherapy and targeted therapy after recurrence and metastasis for hereditary leiomyomatosis and renal cell cancer-a case report." 01/01/2021 - "Complete Response of Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)-Associated Renal Cell Carcinoma to Pembrolizumab Immunotherapy: A Case Report." 04/01/2007 - "Papillary type 2 RCC described in the context of hereditary leiomyomatosis and renal cell cancer (HLRCC), an autosomal dominant syndrome attributable to a mutation in the fumarate hydratase (FH) gene on chromosome 1. Radical nephrectomy, immunotherapy, chemotherapy and repeat surgical debulking. " 01/01/2021 - "Complete response of hereditary leiomyomatosis and renal cell cancer (HLRCC)-associated renal cell carcinoma to nivolumab and ipilimumab combination immunotherapy by: a case report."
2.	Therapeutics 04/01/2020 - "The preliminary outcome of the combination of immunotherapy and targeted therapy after recurrence and metastasis for hereditary leiomyomatosis and renal cell cancer-a case report." 03/01/2011 - "pRCC-2 arising in a patient with a novel germline FH mutation and de novo hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome progressing after mTORC1 inhibitor therapy. " 01/01/2023 - "Succinate dehydrogenase (dSDH)-deficient tumors, including pheochromocytoma/paraganglioma, hereditary leiomyomatosis and renal cell cancer-associated renal cell carcinoma (HLRCC-RCC), and gastrointestinal stromal tumors (GIST) without KIT or platelet-derived growth factor receptor alpha mutations are often resistant to cytotoxic chemotherapy, radiotherapy, and many targeted therapies. "
3.	Nephrectomy 03/17/2016 - "Radical nephrectomy and regional lymph node dissection for locally advanced type 2 papillary renal cell carcinoma in an at-risk individual from a family with hereditary leiomyomatosis and renal cell cancer: a case report." 04/01/2007 - "Papillary type 2 RCC described in the context of hereditary leiomyomatosis and renal cell cancer (HLRCC), an autosomal dominant syndrome attributable to a mutation in the fumarate hydratase (FH) gene on chromosome 1. Radical nephrectomy, immunotherapy, chemotherapy and repeat surgical debulking. " 01/01/2020 - "A Case of Metastatic Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome-Associated Renal Cell Carcinoma Treated with a Sequence of Axitinib and Nivolumab Following Cytoreductive Nephrectomy."
4.	Drug Therapy (Chemotherapy) 04/01/2007 - "Papillary type 2 RCC described in the context of hereditary leiomyomatosis and renal cell cancer (HLRCC), an autosomal dominant syndrome attributable to a mutation in the fumarate hydratase (FH) gene on chromosome 1. Radical nephrectomy, immunotherapy, chemotherapy and repeat surgical debulking. " 01/01/2023 - "Succinate dehydrogenase (dSDH)-deficient tumors, including pheochromocytoma/paraganglioma, hereditary leiomyomatosis and renal cell cancer-associated renal cell carcinoma (HLRCC-RCC), and gastrointestinal stromal tumors (GIST) without KIT or platelet-derived growth factor receptor alpha mutations are often resistant to cytotoxic chemotherapy, radiotherapy, and many targeted therapies. "
5.	Gas Lasers 07/01/2020 - "Fractional CO2 Laser Treatment for Cutaneous Leiomyomas in a Patient with Reed's Syndrome."