Article Text
PDF
Abstract
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.
- ALS
- genetics
- motor neurone disease
- neurogenetics
- clinical neurology
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
Statistics from Altmetric.com
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors TD drafted the manuscript and figures. JS, EE, RM, AT, KT edited the manuscript. MRT conceived and edited the manuscript.
Funding TD is funded by a NHMRC CJ Martin Post-Doctoral Fellowship. EE is funded by the Association of British Neurologists and Dunhill Medical Trust Fellowship. AT is funded by the Medical Research Council and Motor Neurone Disease Association Lady Edith Wolfson Clinician Scientist Fellowship. MRT receives funding support from the Motor Neuron Disease Association.
Map disclaimer The depiction of boundaries on this map does not imply the expression of any opinion whatsoever on the part of BMJ (or any member of its group) concerning the legal status of any country, territory, jurisdiction or area or of its authorities. This map is provided without any warranty of any kind, either express or implied.
Competing interests None declared.
Provenance and peer review Commissioned and externally reviewed by Huw Morris, London, UK.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
Linked Articles
- Editors’ commentary
Other content recommended for you
- Comprehensive analysis of the mutation spectrum in 301 German ALS families
- Value of systematic genetic screening of patients with amyotrophic lateral sclerosis
- Analysis of known amyotrophic lateral sclerosis and frontotemporal dementia genes reveals a substantial genetic burden in patients manifesting both diseases not carrying the C9orf72 expansion mutation
- Genetics insight into the amyotrophic lateral sclerosis/frontotemporal dementia spectrum
- Genotype–phenotype correlation of SQSTM1 variants in patients with amyotrophic lateral sclerosis
- CHMP2B mutations are not a common cause of familial or sporadic amyotrophic lateral sclerosis
- Pathophysiological insights into ALS with C9ORF72 expansions
- Genetic testing and reproductive choice in neurological disorders
- Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis
- Effect of familial clustering in the genetic screening of 235 French ALS families