Over the past two decades advances in genomic technologies have transformed knowledge of the genetic basis of phaeochromocytoma and paraganglioma (PPGL). Though traditional teaching suggested that inherited cases accounted for only 10% of all phaeochromocytoma diagnosis, current estimates are at least three times this proportion. Inherited PPGL is a highly genetically heterogeneous disorder but the most frequently results from inactivating variants in genes encoding subunits of succinate dehydrogenase. Expanding knowledge of the genetics of PPGL has been translated into clinical practice by the provision of widespread testing for inherited PPGL. In this review, we explore how the molecular stratification of PPGL is being utilized to enable more personalized strategies for investigation, surveillance and management of affected individuals and their families. Translating recent genetic research advances into clinical service can not only bring benefits through more accurate diagnosis and risk prediction but also challenges when there is a suboptimal evidence base for the clinical consequences or significance of rare genotypes. In such cases, clinical, biochemical, pathological and functional imaging assessments can all contribute to more accurate interpretation and clinical management.

中文翻译：

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遗传性和散发性嗜铬细胞瘤和副神经节瘤的遗传分层：对精准医学的影响

在过去的二十年中，基因组技术的进步改变了对嗜铬细胞瘤和副神经节瘤 (PPGL) 遗传基础的认识。尽管传统教学表明遗传病例仅占所有嗜铬细胞瘤诊断的 10%，但目前的估计至少是这个比例的三倍。遗传性 PPGL 是一种高度遗传异质的疾病，但最常见的原因是编码琥珀酸脱氢酶亚基的基因中的变异失活。通过提供对遗传性 PPGL 的广泛检测，对 PPGL 遗传学的扩展知识已转化为临床实践。在这篇综述中，我们探讨了如何利用 PPGL 的分子分层来实现更个性化的调查策略，监测和管理受影响的个人及其家庭。将最近的基因研究进展转化为临床服务不仅可以通过更准确的诊断和风险预测带来好处，而且在罕见基因型的临床后果或意义存在次优证据基础时也面临挑战。在这种情况下，临床、生化、病理和功能成像评估都有助于更准确的解释和临床管理。