A survey of current practice in genetic testing in amyotrophic lateral sclerosis in the UK and Republic of Ireland: implications for future planning

<i>Objective:</i> To determine the current practice in genetic testing for patients with apparently sporadic motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) and asymptomatic at-risk relatives of familial MND/ALS patients seen in specialized care centers in the UK. <i>Methods:</i> An online survey with 10 questions distributed to specialist healthcare professionals with a role in requesting genetic testing working at MND/ALS care centers. <i>Results:</i> Considerable variation in practice was found. Almost 30% of respondents reported some discomfort in discussing genetic testing with MND/ALS patients and a majority (77%) did not think that all patients with apparently sporadic disease should be routinely offered genetic testing at present. Particular concerns were identified in relation to testing asymptomatic at-risk individuals and the majority view was that clinical genetics services should have a role in supporting genetic testing in MND/ALS, especially in asymptomatic individuals at-risk of carrying pathogenic variants. <i>Conclusions:</i> Variation in practice in genetic testing among MND/ALS clinics may be driven by differences in experience and perceived competence, compounded by the increasing complexity of the genetic underpinnings of MND/ALS. Clear and accessible guidelines for referral pathways between MND/ALS clinics and clinical genetics may be the best way to standardize and improve current practice, ensuring that patients and relatives receive optimal and geographically equitable support.

研究目标：本研究旨在明确英国专科诊疗中心内，针对疑似散发性运动神经元病/肌萎缩侧索硬化（Motor Neurone Disease/Amyotrophic Lateral Sclerosis, MND/ALS）患者，以及家族性MND/ALS患者的无症状高危亲属开展基因检测的当前临床实践现状。
研究方法：向在MND/ALS诊疗中心任职、承担基因检测申请职责的专科医护人员发放包含10个问题的线上调查问卷。
研究结果：临床实践存在显著异质性。近30%的受访者表示与MND/ALS患者沟通基因检测相关事项时存在一定不适感；多数（77%）受访者认为当前无需为所有疑似散发性患者常规提供基因检测。研究还发现针对无症状高危个体的检测存在特定顾虑，绝大多数观点认为临床遗传学服务应在MND/ALS的基因检测工作中发挥支持作用，尤其针对携带致病变异的无症状高危人群。
研究结论：MND/ALS诊疗中心间基因检测实践的差异，可能源于临床经验与感知胜任力的不同，加之MND/ALS遗传基础的日益复杂。建立清晰易懂的MND/ALS诊疗中心与临床遗传学机构间的转诊路径指南，或可成为规范并优化当前临床实践的最佳方案，确保患者及亲属获得最优且地域公平的医疗支持。