Genetic testing in motor neuron disease and frontotemporal dementia: a 5-year multicentre evaluation

• Published in: Journal of medical genetics Vol. 59; no. 6; pp. 544 - 548
• Main Authors: Cairns, Lauren M, Rankin, Julia, Hamad, Asma, Cooper, Nicola, Merrifield, Katrina, Jain, Vani, Rosser, Elisabeth, Rogers, Megan, Buston, Sarah, Stopford, Cheryl, Jones, Gabriela, Lefroy, Henrietta, Németh, Andrea H, Holden, Simon, Douglas, Andrew G L
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.06.2022; BMJ Publishing Group LTD
• Subjects: Age; Amyotrophic lateral sclerosis; Counseling; Dementia; Dementia disorders; Family medical history; Frontotemporal dementia; Genetic counseling; Genetic screening; Genetic testing; Genetics; Motor neuron diseases; Motor neurone disease; Mutation; Neurodegenerative diseases; Neurogenetics; Neurology; Patients; Phenotypes; United Kingdom > UK; neurodegenerative diseases; dementia; genetic testing; motor neurone disease
• ISSN: 0022-2593; 1468-6244
• DOI: 10.1136/jmedgenet-2021-107776

IntroductionMotor 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.ObjectiveWe sought to ascertain UK clinical genetics testing practice in MND/FTD referrals, with the aim of helping inform guideline development.MethodsMND/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.Results301 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.ConclusionWe propose pragmatic MND/FTD genetic testing guidelines based on appropriate genetic counselling.