Alam N Afrina, Barclay Ella, Rowan Andrew J, Tyrer Jonathan P, Calonje Eduardo, Manek Sanjiv, Kelsell David, Leigh Irene, Olpin Simon, Tomlinson Ian P M
Molecular and Population Genetics Laboratory, Cancer Research UK, London.
Arch Dermatol. 2005 Feb;141(2):199-206. doi: 10.1001/archderm.141.2.199.
To investigate the clinical features of the multiple cutaneous and uterine leiomyomatosis (MCUL) syndrome, including the hereditary leiomyomatosis and renal cell cancer syndrome.
A case series of patients with multiple skin leiomyomas solicited via a circular letter to dermatologists.
Research institute.
A total of 108 affected individuals, including 46 probands and 62 affected relatives.
The proportion of probands with underlying fumarate hydratase (FH) mutations, the penetrance of FH mutations, and clinicopathologic features of MCUL.
Forty-one (89%) of 46 probands with multiple skin leiomyomas had evidence of germline FH mutations, which were highly penetrant. All 26 male mutation carriers had skin leiomyomas. Of 67 women with FH mutations, 46 (69%) had both skin and uterine leiomyomas; 10 (15%) had only skin leiomyomas; 5 (7%) had only uterine leiomyomas; and 6 (9%) were clinically unaffected. Patients presented with skin leiomyomas at a mean age of 24 years and had a mean of 25 lesions. Forty-one individuals (89%) reported painful lesions, particularly in response to cold or trauma. Fibroids were histologically unremarkable, highly symptomatic, and associated with a high risk of early hysterectomy. One individual had a very aggressive collecting duct renal cancer. The G354R FH mutation predisposed patients to uterine fibroids without skin leiomyomas (P = .03). Many patients with skin leiomyomas had not previously presented for medical attention. Fibroids were rarely recognized as cases of MCUL.
Highly penetrant FH mutations underlie MCUL. Increased clinical awareness is important because of the associated risk of severe uterine fibroids and, in some cases, aggressive renal cancer.
研究多发性皮肤和子宫平滑肌瘤综合征（MCUL）的临床特征，包括遗传性平滑肌瘤病和肾细胞癌综合征。
通过给皮肤科医生的通函征集多发性皮肤平滑肌瘤患者的病例系列。
研究所。
共108例受影响个体，包括46例先证者和62例受影响亲属。
有潜在延胡索酸水合酶（FH）突变的先证者比例、FH突变的外显率以及MCUL的临床病理特征。
46例有多发性皮肤平滑肌瘤的先证者中，41例（89%）有生殖系FH突变证据，这些突变具有高度外显率。所有26名男性突变携带者均有皮肤平滑肌瘤。在67名有FH突变的女性中，46例（69%）既有皮肤平滑肌瘤又有子宫平滑肌瘤；10例（15%）仅有皮肤平滑肌瘤；5例（7%）仅有子宫平滑肌瘤；6例（9%）临床上未受影响。患者出现皮肤平滑肌瘤的平均年龄为24岁，平均有25个病灶。41例（89%）报告病灶疼痛，尤其是对寒冷或创伤有反应时。肌瘤在组织学上无明显异常，但症状严重，且与早期子宫切除术的高风险相关。1例患者患有侵袭性很强的集合管肾癌。G354R FH突变使患者易患无皮肤平滑肌瘤但有子宫肌瘤的疾病（P = 0.03）。许多有皮肤平滑肌瘤的患者此前未就医。肌瘤很少被诊断为MCUL病例。
高度外显的FH突变是MCUL的基础。提高临床意识很重要，因为存在严重子宫肌瘤以及在某些情况下侵袭性肾癌的相关风险。
