Type 2 Segmental Manifestation of Cutaneous Leiomyomatosis in Four Unrelated Women with Additional Uterine Leiomyomas (Reed’s Syndrome)

Ritzmann, S.; Hanneken, S.; Neumann, Norbert; Ruzicka, Thomas; Kruse, Roland

doi:10.1159/000089031

Cited by 16 publications

(15 citation statements)

References 16 publications

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“…In line with previous reports (21–23), a diffuse and symmetric as well as a segmental manifestation pattern of leiomyomas could be observed in the patients and families studied here (Fig. 3a,b).…”

Section: Discussionsupporting

confidence: 93%

Diffuse and segmental variants of cutaneous leiomyomatosis: novel mutations in the fumarate hydratase gene and review of the literature

Badeloe

Geel

Steensel

et al. 2006

Experimental Dermatology

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Multiple cutaneous and uterine leiomyomatosis (MCUL; OMIM 150800) is an autosomal dominantly inherited disease characterized by leiomyomas of the skin and uterine leiomyomas. Recently, association of MCUL with different forms of renal cancer has been described. This syndrome is referred to as hereditary leiomyomatosis and renal cell cancer (OMIM 605839). Both disorders result from heterozygous germline mutations in the fumarate hydratase (FH) gene that may function as a tumor suppressor. Interestingly, cutaneous leiomyomas do not only manifest in a diffuse and symmetric fashion. Rather frequently, a segmental or band-like manifestation pattern can be observed, usually following the lines of Blaschko. Here, we sought to elucidate the molecular basis of diffuse and segmental cutaneous leiomyomatosis in six unrelated Dutch and Spanish patients and their families. We identified six novel FH mutations, including one missense and one nonsense mutation, two deletions and two splice-site mutations. The segmental phenotype that was observed in various patients with FH mutations most likely reflects a type 2 segmental manifestation of cutaneous leiomyomatosis as previously also described for other autosomal dominantly inherited skin diseases. The results presented here extend the current data on the molecular basis of familial cutaneous leiomyomatosis and comprise, to the best of our knowledge, the first genetic study in Dutch and Spanish patients with this disorder. In addition, we review the clinical and molecular aspects of the disease.

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Section: Discussionsupporting

confidence: 93%

Diffuse and segmental variants of cutaneous leiomyomatosis: novel mutations in the fumarate hydratase gene and review of the literature

Badeloe

Geel

Steensel

et al. 2006

Experimental Dermatology

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“…Happle [8] proposes the distinction between type 1 segmental involvement, where the segmental lesions show the same severity as in the non-mosaic trait, and type 2 segmental manifestation, where the intensity of involvement observed in the circumscribed area is far more pronounced. There are several reports of cutaneous leiomyomatosis presenting with this type 2 segmental distribution [9,10,11,12]. Together with the above-mentioned hypothesis of a two-hit model of tumorigenesis, this strongly suggests that loss of heterozygosity at the FH locus in the involved skin is due to a second event occurring at a post-zygotic stage.…”

Section: Introductionmentioning

confidence: 82%

Evidence for a New Fumarate Hydratase Gene Mutation in a Unilateral Type 2 Segmental Leiomyomatosis

et al. 2010

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Background: Multiple cutaneous and uterine leiomyomata syndrome (MCUL; MIM 150800) is a rare condition that sometimes predisposes to renal cancer. It is caused by deleterious mutations in the fumarate hydratase (FH) gene. In many patients, skin leiomyomas have been reported to develop according to a segmental type 1 or type 2 distribution. We report a patient showing multiple leiomyomas distributed according to a segmental type 2 distribution and covering several areas exclusively on the left side of his body. Objective: To search for a specific mutation in the FH gene associated with this phenotype. Methods: Genomic DNA from peripheral blood leucocytes of the proband was sequenced and screened for mutation of the FH gene. Results: Heterozygosity for an as yet undescribed mutation c.695delG, leading to a truncated protein p.Gly232AspfsX24, was found. Conclusion:We report a new mutation in the FH gene and discuss the unusual pattern of purely unilateral distribution in the present case.

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“…They are distributed as clusters, scattered or both [5,11]. Also band-like or segmental (type 2) manifestation has been described [13]. Typical of these tumors is that they cause pain, usually in response to temperature changes and touch.…”

Section: Cutaneous Tumorsmentioning

confidence: 99%

“…To relieve pain, therapy of multiple painful lesions with nitroglycerol, calcium channel blockers, a-adrenoreceptor blockers, analgesics, antidepressants, antiepileptics or a combination of these drugs has been successful in some patients [13]. Topical treatment options include nitroglycerol, anti-cholinergic agent, anesthetic, cryotherapy and CO 2 laser ablation [13]. Of note, despite the commonly experienced pain, the majority of the patients find the lesions tolerable [5].…”

Section: Leiomyomasmentioning

confidence: 99%

Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics

2011

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Hereditary leiomyomatosis and renal cell cancer (HLRCC, also known as multiple cutaneous and uterine leiomyomatosis, MCUL) is a highly penetrant autosomal dominant tumor predisposition syndrome characterized by benign leiomyomas of the skin and the uterus. Renal cell carcinomas, occurring in a subset of the HLRCC families, are exceptionally aggressive. Therefore careful, frequent surveillance strategies are recommended. Association of malignant smooth-muscle tumors, leiomyosarcomas, with HLRCC has been observed but the risk appears to be smaller than initially estimated. To date inactivating heterozygous mutations in the fumarate hydratase (FH, fumarase) gene, predisposing to HLRCC, have been found in approximately 180 families worldwide. The most extensively studied hypothesis on molecular mechanisms of HLRCC tumorigenesis is activation of the hypoxia pathway due to aberrant stabilization of the HIF1 transcription factor. HIF1 regulates transcription of genes relevant for vascularization, glucose transport and glycolysis, processes that facilitate tumor growth. However, additional mechanisms underlying tumor formation are likely to exist.

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Type 2 Segmental Manifestation of Cutaneous Leiomyomatosis in Four Unrelated Women with Additional Uterine Leiomyomas (Reed’s Syndrome)

Cited by 16 publications

References 16 publications

Diffuse and segmental variants of cutaneous leiomyomatosis: novel mutations in the fumarate hydratase gene and review of the literature

Diffuse and segmental variants of cutaneous leiomyomatosis: novel mutations in the fumarate hydratase gene and review of the literature

Evidence for a New Fumarate Hydratase Gene Mutation in a Unilateral Type 2 Segmental Leiomyomatosis

Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics

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