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

Cairns, Lauren M; Rankin, Julia; Hamad, Asma; Cooper, N; 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.

doi:10.1136/jmedgenet-2021-107776

Cited by 3 publications

(3 citation statements)

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“…It is easy to underestimate the sense of disappointment this lack of molecular certainty entails, and individuals must be counselled about this before testing. Within the much larger apparently sporadic case population (~90%), a pathological variant will be identified in at least 10% of cases, with some studies proposing more than a fifth with clinically actionable findings 41 42. Even using the conservative estimate, 10% of the apparently sporadic cases of ALS is a greater number than 70% of the cases who report a family history.…”

Section: Introductionmentioning

confidence: 99%

Genetic testing in motor neurone disease

et al. 2022

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A minority (10%–15%) of cases of amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease (MND), are currently attributable to pathological variants in a single identifiable gene. With the emergence of new therapies targeting specific genetic subtypes of ALS, there is an increasing role for routine genetic testing for all those with a definite diagnosis. However, potential harm to both affected individuals and particularly to asymptomatic relatives can arise from the indiscriminate use of genetic screening, not least because of uncertainties around incomplete penetrance and variants of unknown significance. The most common hereditary cause of ALS, an intronic hexanucleotide repeat expansion in C9ORF72, may be associated with frontotemporal dementia independently within the same pedigree. The boundary of what constitutes a possible family history of MND has therefore extended to include dementia and associated psychiatric presentations. Notwithstanding the important role of clinical genetics specialists, all neurologists need a basic understanding of the current place of genetic testing in MND, which holds lessons for other neurological disorders.

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Section: Introductionmentioning

confidence: 99%

Genetic testing in motor neurone disease

et al. 2022

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“…1 It is predicted that increasing numbers of people with MND will access genetic testing, a consequence of widening eligibility criteria and genetically targeted clinical trials (with one genetically targeted therapy suggesting clinical benefit). [2][3][4] This means more family members will become aware of their increased risk of developing the condition. The genetics of MND are complex, 5 but it is suggested that in up to 20% of people with MND, a pathogenic variant can be identified.…”

Section: Introductionmentioning

confidence: 99%

“…The typical survival from symptom onset is 2–5 years 1 . It is predicted that increasing numbers of people with MND will access genetic testing, a consequence of widening eligibility criteria and genetically targeted clinical trials (with one genetically targeted therapy suggesting clinical benefit) 2–4 . This means more family members will become aware of their increased risk of developing the condition.…”

Section: Introductionmentioning

confidence: 99%

Fluctuating salience in those living with genetic risk of motor neuron disease: A qualitative interview study

Howard,

Mazanderani,

Keenan

et al. 2024

Health Expectations

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BackgroundMotor neuron disease (MND) (also known as amyotrophic lateral sclerosis) is a life‐limiting neurodegenerative condition. In up to 20% of people with MND, a pathogenic variant associated with autosomal dominant inheritance can be identified. Children of people carrying a pathogenic variant have a 50% chance of inheriting this and a higher, although harder to predict, chance of developing the disease compared to the general adult population. This paper explores the experience of living with the genetic risk of MND.MethodsWe undertook a UK‐based interview study with 35 individuals, including: 7 people living with genetically‐mediated forms of MND; 24 asymptomatic relatives, the majority of whom had an increased risk of developing the disease; and 4 unrelated partners.ResultsWe explore how individuals make sense of genetic risk, unpacking the interplay between genetic knowledge, personal perception, experiences of the disease in the family, age and life stage and the implications that living with risk has for different aspects of their lives. We balance an emphasis on the emotional and psychological impact described by participants, with a recognition that the salience of risk fluctuates over time. Furthermore, we highlight the diverse strategies and approaches people employ to live well in the face of uncertainty and the complex ways they engage with the possibility of developing symptoms in the future. Finally, we outline the need for open‐ended, tailored support and information provision.ConclusionsDrawing on wider literature on genetic risk, we foreground how knowledge of MND risk can disrupt individuals' taken‐for‐granted assumptions on life and perceptions of the future, but also its contextuality, whereby its relevance becomes more prominent at critical junctures. This research has been used in the development of a public‐facing resource on the healthtalk.org website.Patient or Public ContributionPeople with experience of living with genetic risk were involved throughout the design and conduct of the study and advised on aspects including the topic guide, sampling and recruitment and the developing analysis. Two patient and public involvement contributors joined a formal advisory panel.

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

Oliveira

Soma

Baker

et al. 2022

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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This survey has 10 questions in addition to demographic data. It should take less than 5 minutes to complete.This survey aims to determine current UK practice for genetic testing in patients diagnosed with apparently sporadic Motor Neuron Disease/Amyotrophic Lateral Sclerosis (MND/ALS). This is particularly relevant in the context of upcoming changes in the provision of genetic testing in the NHS and emerging therapies targeting monogenic MND.It does not address the acknowledged absence of consensus for the definition of familial MND/ALS or the role of genetic testing in MND/ALS diagnostic criteria. A single question regarding the interpretation of a family history of dementia is asked.Respondents' names are required to ensure that only one response per individual is analysed. All responses will be anonymised.

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

Cited by 3 publications

References 19 publications

Genetic testing in motor neurone disease

Genetic testing in motor neurone disease

Fluctuating salience in those living with genetic risk of motor neuron disease: A qualitative interview study

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

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