嗜铬细胞瘤和副神经节瘤(PPGL)是罕见的肿瘤,至少30%是遗传性综合征的一部分。大约20%的遗传性PPGL是由琥珀酸脱氢酶复合物(SDHx)基因中的致病性种系变体引起的,TMEM127或MAX。在此,我们基于全面的文献综述,提出了有关家庭成员遗传检测及其监测的指南。无论患者和家庭特征如何,建议对所有PPGL病例进行种系变异的基因检测。至少,FH,NF1,RET,SDHB,应测试SDHD和VHL。此外,测试MEN1、SDHA、SDHAF2,SDHC,建议使用TMEM127和MAX。应向健康的一级亲属(在SDHD和SDHAF2的情况下为二级亲属,这是母体印记)提供载体测试。应通过每年对甲氧基-儿茶酚胺进行生化测量以及每两年进行一次快速全身磁共振成像和临床检查来监测致病变异的携带者。监测应在家庭最早发病年龄之前5年开始,因此只有符合监测条件的儿童才应接受症状前基因检测。对15岁以下儿童的监测需要单独设计。我们的指南将为患者管理提供一个框架,可以通过国家注册和/或随访研究跟踪结果。加上对这种疾病的更好的见解,这可以优化监测计划,以最大限度地减少焦虑和医疗并发症,同时确保早期疾病检测。
Pheochromocytoma and paraganglioma (PPGL) are rare tumours and at least 30% are part of hereditary syndromes. Approximately 20% of hereditary PPGL are caused by pathogenic germ line variants in genes of the succinate dehydrogenase complex (SDHx), TMEM127 or MAX. Herein we present
guidelines regarding genetic testing of family members and their surveillance based on a thorough literature review. All cases of PPGL are recommended genetic testing for germ line variants regardless of patient and family characteristics. At minimum, FH, NF1, RET, SDHB, SDHD and VHL should be tested. In addition, testing of MEN1, SDHA, SDHAF2, SDHC, TMEM127 and MAX is recommended. Healthy first-degree relatives (and second-degree relatives in the case of SDHD and SDHAF2 which are maternally imprinted) should be offered carrier testing. Carriers of pathogenic variants should be offered surveillance with annual biochemical measurements of methoxy-catecholamines and bi-annual rapid whole-body magnetic resonance imaging and clinical examination. Surveillance should start 5 years before the earliest age of onset in the family and thus only children eligible for surveillance should be offered pre-symptomatic genetic testing. The surveillance of children younger than 15 years needs to be individually designed. Our
guidelines will provide a framework for patient management with the possibility to follow outcome via national registries and/or follow-up studies. Together with improved insights into the disease, this may enable optimisation of the surveillance scheme in order to minimise both anxiety and medical complications while ensuring early disease detection.