Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers
Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers
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DOI：
10.1111/j.1365-2265.2008.03274.x
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发表时间：
2008-10-01
影响因子：
3.2
通讯作者：
Chew, Shern L.
中科院分区：
文献类型：
--
作者：
Srirangalingam, Umasuthan;Walker, Lisa;Chew, Shern L.
目的高达25%的嗜铬细胞瘤和副神经节瘤是家族性的，可由琥珀酸脱氢酶（SDH）基因突变引起。本研究的目的是描述SDH-B基因突变受试者的临床表现。设计回顾性病例系列。1975年至2007年间随访了32例伴有SDH-B基因突变的患者。平均随访5.8年（SD 7.4，范围0-31）。伦敦圣巴塞洛缪医院和其他英国中心的病人。临床表现、基因突变、肿瘤位置、儿茶酚胺分泌、临床病程和处理的特点。结果32例患者中有16例（50%）存在疾病。注意到两个先前未描述的SDH-B基因突变。只有18%的调查对象有明显的家族病史。诊断时平均年龄为34岁（标准差15.4，范围10-62）。50%的受试者在26岁时患病。69%（16人中的11人）患有高血压，80%（15人中的12人）儿茶酚胺/代谢物分泌升高。24%（6 / 25）肿瘤位于肾上腺，76%（19 / 25）位于肾上腺外。16例中有3例（19%）为多灶性疾病。转移性副神经节瘤发生率为31%（5 / 16）。一名受试者发展为转移性II型乳头状肾细胞癌。队列恶性肿瘤发生率为19%（6 / 32）。2例无高血压的受试者存在大血管疾病。结论SDH-B突变携带者发病早，且以肾上腺外部位为主。疾病外显率不完全。转移性疾病是突出的，但水平低于以前的报道。临床表现可包括乳头状肾细胞癌和大血管病变。
Objective Phaeochromocytomas and paragangliomas are familial in up to 25% of cases and can result from succinate dehydrogenase (SDH) gene mutations. The aim of this study was to describe the clinical manifestations of subjects with SDH-B gene mutations.Design Retrospective case-series.Patients Thirty-two subjects with SDH-B gene mutations followed up between 1975 and 2007. Mean follow-up of 5.8 years (SD 7.4, range 0-31). Patients seen at St Bartholomew's Hospital, London and other UK centres.Measurements Features of clinical presentation, genetic mutations, tumour location, catecholamine secretion, clinical course and management.Results Sixteen of 32 subjects (50%) were affected by disease. Two previously undescribed mutations in the SDH-B gene were noted. A family history of disease was apparent in only 18% of index subjects. Mean age at diagnosis was 34 years (SD 15.4, range 10-62). 50% of affected subjects had disease by the age of 26 years. 69% (11 of 16) were hypertensive and 80% (12 of 15) had elevated secretions of catecholamines/metabolites. 24% (6 of 25) of tumours were located in the adrenal and 76% (19 of 25) were extra-adrenal. 19% (3 of 16) had multifocal disease. Metastatic paragangliomas developed in 31% (5 of 16). One subject developed a metastatic type II papillary renal cell carcinoma. The cohort malignancy rate was 19% (6 of 32). Macrovascular disease was noted in two subjects without hypertension.Conclusion SDH-B mutation carriers develop disease early and predominantly in extra-adrenal locations. Disease penetrance is incomplete. Metastatic disease is prominent but levels are less than previously reported. Clinical manifestations may include papillary renal cell carcinoma and macrovascular disease.