Diagnosis of genetic cause in motor neuron disease patients could be missed due to age limits on genetic testing

Based on the results of a new study published in Brainresearchers from the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King’s College London are calling for a complete rethink of national guidelines on who has access to genetic testing for amyotrophic lateral sclerosis (ALS), also known as motor neuron disease. Research suggests that there are hundreds of people with ALS in the UK who lack a genetic basis for their ALS because they do not meet the strict requirements for genetic testing. As guidelines are similar in many countries, this situation will likely be the same internationally, meaning there may be thousands of people unaware of a genetic link to their ALS.

The study estimates that although nearly a quarter of people with ALS who do not have family members with the disease have a genetic link to their ALS, 98% of the time, current guidelines go undetected. As a result, they are not offered adequate genetic counseling and counseling, and would not have access to gene-based therapies, which are likely to be available soon or in trials. The researchers say genetic testing should be open to all patients with ALS, whether or not other family members are affected, and to all age groups.

ALS is a progressive nervous system disease that affects nerve cells in the brain and spinal cord, causing muscle paralysis. About 1 in 300 people will be diagnosed with ALS at some point in their lives, with the average person surviving between two and five years after their symptoms begin. There is currently no cure for ALS.

In some cases, there is an identifiable genetic cause. Given the current restrictive testing guidelines, the researchers wanted to determine the probability of a positive genetic test result in different scenarios to inform how and when genetic testing should be used. They performed two analyzes on global datasets, analyzing the four most common ALS genes and a larger panel of 26 ALS genes.

Their analysis found that by restricting testing in those with no family history to those with symptom onset under the age of 40, under current UK guidelines, 115 out of 117 positive test results were missed. Extrapolating this data to other healthcare systems around the world, they found that potentially thousands of people with ALS are unaware they have a genetic cause for their ALS due to the inaccessibility of testing.

Professor Ammar Al-Chalabi, Professor of Neurology and Complex Disease Genetics at King’s IoPPN and lead author of the study, said: “ALS is a life-destroying disease. Genetic testing means people and their families can access and receive proper advice on genetic counseling and family planning support. Our study found that due to the arbitrary age limits and rules currently in place, many people do not have access to this care and support.”

While the researchers acknowledge that extending the guidelines to more people will be resource-intensive, they argue that countries should aim to offer genetic testing for ALS patients of all ages whenever possible.

dr Puja Mehta, the study’s first author, said: “Our study shows the importance of being able to offer a blood test to people of all ages with ALS to identify a possible genetic cause. In addition to having access to appropriate genetic counseling and support, with the exciting prospect of specific gene-based therapies on the horizon, and with ongoing clinical trials, it becomes even more important for people with ALS to know if they have an identifiable genetic cause.”

dr Nicholas Cole, Research Director of the MND Association, said: “This study, supported by the MND Association, reinforces the suggestion that routine genetic testing should be offered to MND patients, regardless of their age at onset or family history of the disease. Genetic testing could offer more people with MND the opportunity to participate in tailored clinical trials. However, it is imperative that testing is supported by a robust genetic counseling infrastructure to provide tailored support to all who choose to undertake the process.”