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Genetic testing in motor neuron disease and frontotemporal dementia: a 5-year multicentre evaluation
  1. Lauren M Cairns1,
  2. Julia Rankin2,
  3. Asma Hamad3,
  4. Nicola Cooper3,
  5. Katrina Merrifield3,
  6. Vani Jain4,
  7. Elisabeth Rosser5,
  8. Megan Rogers6,
  9. Sarah Buston6,
  10. Cheryl Stopford7,
  11. Gabriela Jones8,
  12. Henrietta Lefroy9,
  13. Andrea H Németh10,
  14. Simon Holden11,
  15. Andrew G L Douglas1,12
  1. 1Wessex Clinical Genetics Service, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  2. 2Peninsula Clinical Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
  3. 3Clinical Genetics Unit, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
  4. 4All Wales Medical Genetics Service, University Hospital Wales, Cardiff, UK
  5. 5Clinical Genetics Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
  6. 6Bristol Regional Clinical Genetics Service, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
  7. 7Yorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  8. 8Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, UK
  9. 9Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
  10. 10Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK
  11. 11Clinical Genetics, Addenbrooke's Treatment Centre, Cambridge, UK
  12. 12Human Development and Health, University of Southampton, Southampton, UK
  1. Correspondence to Dr Andrew G L Douglas, Human Development and Health, University of Southampton, Southampton, UK; a.g.douglas{at}soton.ac.uk

Abstract

Introduction 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.

Objective We sought to ascertain UK clinical genetics testing practice in MND/FTD referrals, with the aim of helping inform guideline development.

Methods 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.

Results 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.

Conclusion We propose pragmatic MND/FTD genetic testing guidelines based on appropriate genetic counselling.

  • motor neurone disease
  • genetic testing
  • dementia
  • neurodegenerative diseases

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Footnotes

  • Contributors All authors contributed to the collection of data for this manuscript. The manuscript was drafted by LMC and AGLD and all authors had an opportunity to review and comment on the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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