Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes
Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes
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DOI：
10.1210/jc.2005-1862
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发表时间：
2006-03-01
影响因子：
5.8
通讯作者：
Robinson, BG
中科院分区：
文献类型：
--
作者：
Benn, DE;Gimenez-Roqueplo, AP;Robinson, BG
背景：在嗜铬细胞瘤/副神经节瘤综合征中，琥珀酸脱氢酶（SDH）编码肽的基因突变的鉴定需要明确阐明基因型-表型关联。目的：我们的目的是确定嗜铬细胞瘤/副神经节瘤综合征和琥珀酸脱氢酶亚基B （SDHB）或亚基D （SDHD）突变患者队列的基因型-表型相关性。设计、环境和参与者：国际SDH联盟研究了来自62个嗜铬细胞瘤/副神经节瘤综合征和SDHB或SDHD突变家族的116例个体（83例受影响，33例临床未受影响）。临床数据收集于2003年8月至2004年9月，来自澳大利亚、法国、新西兰、德国、美国、加拿大和苏格兰的三级转诊中心。主要结局指标：收集嗜铬细胞瘤和/或副神经节瘤患者的发病、诊断、基因检测、手术、病理和疾病进展方面的数据。临床特征评估基因型-表型关联的证据，并确定外显率。结果：SDHB突变携带者比SDHD突变携带者更容易发生肾上腺外嗜铬细胞瘤和恶性疾病，而SDHD突变携带者更容易发生头颈部副神经节瘤和多发性肿瘤。对于指标病例，43例SDHB突变携带者与19例SDHD突变携带者首次诊断时间无差异（分别为34年与28年，P=0.3）。然而，当包括所有突变携带者（n=112）时，SDHB和SDHD突变携带者的估计年龄相关外显率不同（P=0.008）。结论：在临床随访中，SDHB突变相关疾病的特征包括发病年龄较晚，肾上腺外（腹部或胸部）肿瘤，恶性肿瘤发生率较高。相反，除了头颈部副神经节瘤外，对于多灶性肿瘤，罕见的恶性肿瘤，以及肾上腺外嗜铬细胞瘤的可能性，应观察sddd突变携带者。
Context: The identification of mutations in genes encoding peptides of succinate dehydrogenase (SDH) in pheochromocytoma/paraganglioma syndromes has necessitated clear elucidation of genotype-phenotype associations.Objective: Our objective was to determine genotype-phenotype associations in a cohort of patients with pheochromocytoma/paraganglioma syndromes and succinate dehydrogenase subunit B (SDHB) or subunit D (SDHD) mutations.Design, Setting, and Participants: The International SDH Consortium studied 116 individuals (83 affected and 33 clinically unaffected) from 62 families with pheochromocytoma/paraganglioma syndromes and SDHB or SDHD mutations. Clinical data were collected between August 2003 and September 2004 from tertiary referral centers in Australia, France, New Zealand, Germany, United States, Canada, and Scotland.Main Outcome Measures: Data were collected on patients with pheochromocytomas and/or paragangliomas with respect to onset of disease, diagnosis, genetic testing, surgery, pathology, and disease progression. Clinical features were evaluated for evidence of genotype-phenotype associations, and penetrance was determined.Results: SDHB mutation carriers were more likely than SDHD mutation carriers to develop extraadrenal pheochromocytomas and malignant disease, whereas SDHD mutation carriers had a greater propensity to develop head and neck paragangliomas and multiple tumors. For the index cases, there was no difference between 43 SDHB and 19 SDHD mutation carriers in the time to first diagnosis (34 vs. 28 yr, respectively; P=0.3). However, when all mutation carriers were included (n=112), the estimated age-related penetrance was different for SDHB vs. SDHD mutation carriers (P=0.008).Conclusions: For clinical follow-up, features of SDHB mutation-associated disease include a later age of onset, extraadrenal (abdominal or thoracic) tumors, and a higher rate of malignancy. In contrast, SDHD mutation carriers, in addition to head and neck paragangliomas, should be observed for multifocal tumors, infrequent malignancy, and the possibility of extraadrenal pheochromocytoma.