Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), Section of Medical Genetics, University of Genoa, c/o DIMI Viale Benedetto XV, 6, 16132, Genova, Italy.
IRCCS Policlinico San Martino, Genova, Italy.
Orphanet J Rare Dis. 2020 Dec 14;15(1):348. doi: 10.1186/s13023-020-01633-z.
Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to organ damage and death. For other late-onset fatal diseases, as Huntington's disease, protocols for pre-symptomatic genetic testing (PST) are available since decades. For ATTRv, limited experience has been reported to date, mostly gathered before the availability of approved therapies. We aimed at developing recommendations for a safe and feasible PST protocol in ATTRv in the era of emerging treatments, taking also into account Italian patients' characteristics and healthcare system rules. After an initial survey on ongoing approaches to PST for ATTRv in Italy, two roundtable meetings were attended by 24 experts from 16 Italian centers involved in the diagnosis and care of this disease. Minimal requirements for PST offer and potential critical issues were highlighted. By November 2019, 457 families affected by ATTRv with 209 molecularly confirmed pre-symptomatic carriers were counted. The median age at PST was 41.3 years of age, regardless of the specific mutation. Half of the Italian centers had a multidisciplinary team, including a neurologist, an internist, a cardiologist, a medical geneticist and a psychologist, although in most cases not all the specialists were available in the same center. A variable number of visits was performed at each site. Experts agreed that PST should be offered only in the context of genetic counselling to at risk individuals aged 18 or older. Advertised commercial options for DNA testing should be avoided. The protocol should consist of several steps, including a preliminary clinical examination, a pre-test information session, an interval time, the genetic test and a post-test session with the disclosure of the test results, in the context of an experienced multidisciplinary team. Recommendations for best timing were also defined. Protocols for PST in the context of ATTRv can be refined to offer at risk individuals the best chance for early diagnosis and timely treatment start, while respecting autonomous decisions and promoting safe psychological adjustment to the genetic result.
遗传性转甲状腺素淀粉样变性病（ATTRv，v 代表变体）是一种迟发性常染色体显性疾病，由转甲状腺素淀粉样纤维的进行性细胞外沉积引起，导致器官损伤和死亡。对于其他迟发性致命疾病，如亨廷顿病，几十年来一直有针对无症状遗传检测（PST）的协议可用。对于 ATTRv，迄今为止，据报道只有有限的经验，而且大多数都是在获得批准的治疗方法之前收集的。我们旨在为在新兴治疗时代的 ATTRv 中制定安全可行的 PST 协议提供建议，同时考虑到意大利患者的特点和医疗保健系统规则。在对意大利目前针对 ATTRv 的 PST 方法进行初步调查后，来自 16 个意大利中心的 24 名专家参加了两次圆桌会议，这些中心参与了这种疾病的诊断和治疗。突出了 PST 提供的最低要求和潜在的关键问题。截至 2019 年 11 月，已经统计了 457 个受 ATTRv 影响的家庭，其中有 209 个分子上确认为无症状前携带者。无论具体突变如何，PST 的中位年龄均为 41.3 岁。一半的意大利中心有一个多学科团队，包括神经病学家、内科医生、心脏病专家、医学遗传学家和心理学家，尽管在大多数情况下，并非所有专家都在同一个中心。每个中心进行的就诊次数不同。专家们一致认为，只有在对 18 岁或以上的高危个体进行基因咨询的情况下，才应提供 PST。应避免宣传用于 DNA 测试的商业选择。该方案应包括多个步骤，包括初步临床检查、测试前信息会议、间隔时间、基因测试以及在经验丰富的多学科团队中进行的测试后会议，以披露测试结果。还为最佳时机制定了建议。可以完善 ATTRv 背景下的 PST 方案，为高危个体提供尽早诊断和及时开始治疗的最佳机会，同时尊重自主决策，并促进对遗传结果的安全心理调整。
