Gómez Ana Milena, Soares Diogo Cordeiro, Costa Alexandre André Balieiro, Pereira Daniele Paixão, Achatz Maria Isabel, Formiga Maria Nirvana
Hospital Universitario San Ignacio, Bogotá, Colombia.
Departamento de Oncogenética, A.C. Camargo Cancer Center, São Paulo, SP, Brasil.
Arch Endocrinol Metab. 2019 Jul 29;63(4):369-375. doi: 10.20945/2359-3997000000145.
Paraganglioma (PGL) and pheochromocytoma (PCC) are rare neuroendocrine tumors that were considered to be predominantly sporadic. However, with the identification of novel susceptibility genes over the last decade, it is currently estimated that up to 40% of cases can occur in the context of a hereditary syndrome. We aimed to characterize PGL/PCC families to exemplify the different scenarios in which hereditary syndromes can be suspected and to emphasize the importance for patients and their families of making an opportune genetic diagnosis.
Retrospective analysis of patients diagnosed with PGL/PCC. Germline mutations were studied using next-generation sequencing panels including SDHA, SDHB, SDHC and SDHD. Clinical data were collected from clinical records, and all patients received genetic counseling.
We describe 4 families with PGL/PCC and germline mutations in SDH complex genes. 2 families have SDHB mutations and 2 SDHD mutations. The clinical presentation of the patients and their families was heterogeneous, with some being atypical according to the literature.
PGL/PCC are more commonly associated with a germline mutation than any other cancer type, therefore, all individuals with these types of tumors should undergo genetic risk evaluation. NGS multigene panel testing is a cost-effective approach given the overlapping phenotypes. Individuals with germline mutations associated with PGL/PCC should undergo lifelong clinical, biochemical and imaging surveillance and their families should undergo genetic counseling. For all these reasons, it is critical that all medical staff can suspect and diagnose these inherited cancer predisposition syndromes.
副神经节瘤（PGL）和嗜铬细胞瘤（PCC）是罕见的神经内分泌肿瘤，以往认为主要是散发性的。然而，随着过去十年中新型易感基因的发现，目前估计高达40%的病例可能发生在遗传性综合征背景下。我们旨在对PGL/PCC家系进行特征分析，以举例说明怀疑存在遗传性综合征的不同情形，并强调对患者及其家属进行及时基因诊断的重要性。
对诊断为PGL/PCC的患者进行回顾性分析。使用包括SDHA、SDHB、SDHC和SDHD在内的下一代测序面板研究种系突变。从临床记录中收集临床数据，所有患者均接受遗传咨询。
我们描述了4个患有PGL/PCC且SDH复合基因存在种系突变的家系。2个家系有SDHB突变，2个家系有SDHD突变。患者及其家属的临床表现具有异质性，根据文献，其中一些表现不典型。
与其他任何癌症类型相比，PGL/PCC更常与种系突变相关，因此，所有患有这些类型肿瘤的个体都应进行遗传风险评估。鉴于表型重叠，NGS多基因面板检测是一种具有成本效益的方法。与PGL/PCC相关的种系突变个体应接受终身临床、生化和影像学监测，其家属应接受遗传咨询。基于所有这些原因，至关重要的是所有医务人员都能够怀疑并诊断这些遗传性癌症易感性综合征。
