RT Journal Article
SR Electronic
T1 Genetic testing in motor neurone disease
JF Practical Neurology
JO Pract Neurol
FD BMJ Publishing Group Ltd
SP 107
OP 116
DO 10.1136/practneurol-2021-002989
VO 22
IS 2
A1 Thanuja Dharmadasa
A1 Jakub Scaber
A1 Evan Edmond
A1 Rachael Marsden
A1 Alexander Thompson
A1 Kevin Talbot
A1 Martin R Turner
YR 2022
UL http://pn.bmj.com/content/22/2/107.abstract
AB 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.