Wessex Clinical Genetics Service, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Peninsula Clinical Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
J Med Genet. 2022 Jun;59(6):544-548. doi: 10.1136/jmedgenet-2021-107776. Epub 2021 May 7.
Motor neuron disease (MND) and frontotemporal dementia (FTD) comprise a neurodegenerative disease spectrum. Genetic testing and counselling is complex in MND/FTD owing to incomplete penetrance, variable phenotype and variants of uncertain significance. Affected patients and unaffected relatives are commonly referred to clinical genetics to consider genetic testing. However, no consensus exists regarding how such genetic testing should best be undertaken and on which patients.
We sought to ascertain UK clinical genetics testing practice in MND/FTD referrals, with the aim of helping inform guideline development.
MND/FTD clinical genetics referrals comprising both affected patients and unaffected relatives between 2012 and 2016 were identified and a standardised proforma used to collate data from clinical records.
301 referrals (70 affected, 231 unaffected) were reviewed across 10 genetics centres. Previously identified familial variants were known in 107 cases and 58% subsequently underwent testing (8 of 8 diagnostic and 54 of 99 predictive). The median number of genetic counselling appointments was 2 for diagnostic and 4 for predictive testing. Importantly, application of current UK Genomic Test Directory eligibility criteria would not have resulted in detection of all pathogenic variants observed in this cohort.
We propose pragmatic MND/FTD genetic testing guidelines based on appropriate genetic counselling.
运动神经元病（MND）和额颞叶痴呆（FTD）构成了神经退行性疾病谱。由于不完全外显率、表型多变和意义未明的变异，MND/FTD 的基因检测和咨询非常复杂。受影响的患者和未受影响的亲属通常会被转介到临床遗传学部门，以考虑进行基因检测。然而，对于如何最好地进行这种基因检测以及对哪些患者进行检测，目前尚无共识。
我们旨在确定英国在 MND/FTD 转诊患者中进行临床遗传学检测的实践情况，以期为指南的制定提供信息。
从 2012 年至 2016 年，我们确定了 MND/FTD 临床遗传学转诊患者，包括受影响的患者和未受影响的亲属，并使用标准化表格从临床记录中收集数据。
在 10 个遗传学中心共回顾了 301 份转诊（70 例为受影响患者，231 例为未受影响亲属）。107 例患者已知存在先前确定的家族变异，其中 58%（8/8 例诊断性和 54/99 例预测性）随后进行了检测。诊断性检测的平均基因咨询预约次数为 2 次，预测性检测的平均预约次数为 4 次。重要的是，应用当前英国基因组测试目录的资格标准，不会发现本队列中观察到的所有致病性变异。
我们根据适当的遗传咨询，提出了实用的 MND/FTD 基因检测指南。
