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January 19, 2018 – Patients suffering from amyotrophic lateral sclerosis (ALS) find value in genetic testing for the disease, whether or not they have a family history of the condition, according to findings from a survey conducted by U.S. researchers, just published in the November 2017 issue of Molecular Genetics & Genomic Medicine.
ALS, also known as Lou Gehrig’s disease, is a specific disease which causes the death of neurons controlling voluntary muscles. ALS is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscles decreasing in size. This results in difficulty speaking, swallowing, and eventually breathing.
The investigators surveyed 449 ALS patients (45 with familial ALS and 404 with sporadic ALS). In all, 156 survey respondents (34.7%) reported that they had been offered genetic testing for ALS and 105 that they had completed it. Of 75 patients who recalled the result, 21 (28%) said the result was a positive disease finding.
Genetic testing had been offered to more than two-thirds of the patients with familial ALS and to less than one-third of the patients with sporadic ALS. Most survey respondents reported good experiences with the genetic testing process, with at least 70% agreeing with most survey statements that described the experience in favorable terms. The survey statements that fell below that threshold were those about whether a doctor/care team had explained what the results mean (59%) and whether the test results were useful to family members (62.5%). Respondents who tested positive for an ALS mutation did not have significantly less favorable responses about their testing experiences, compared to those who tested negative. The authors interpret this finding to mean that getting bad news did not negatively impact (the) perception of the testing process.
For that, it is important to know about the genetic background of ALS as it is known today. About 5–10% of cases are directly inherited from a person’s parents. Overall, first-degree relatives of an individual with ALS have a 1% risk of developing ALS. A defect on chromosome 21, which codes for superoxide dismutase, is associated with about 20% of familial cases of ALS, or about 2% of ALS cases overall. This mutation is believed to be transmitted in an autosomal dominant manner, and has over a hundred different forms of mutation. The most common ALS-causing mutation is a mutant SOD1 gene, seen in North America; this is characterized by an exceptionally rapid progression from onset to death. The most common mutation found in Scandinavian countries, D90A-SOD1, is more slowly progressive than typical ALS, and people with this form of the disorder survive for an average of 11 years. In 2011, a genetic abnormality known as a hexanucleotide repeat was found in a region called C9orf72, which is associated with ALS combined with frontotemporal dementia ALS-FTD, and accounts for some 6% of cases of ALS among white Europeans.
Many patients with ALS have questions about why they developed the condition. ALS genetic testing can help patients understand whether their condition is caused by a known ALS gene. If a harmful change is found in one of these genes, the patient has a genetic form of ALS and could become a candidate for gene-specific clinical trials or other studies. A genetic counselor could then also provide specific information about the chance that children and other family members might carry the same gene.
Also, some specific genetic forms of ALS may be associated with a faster or slower progression of symptoms. In these cases, the genetic testing can help to predict the progression of symptoms, which is another piece of information that patients are interested in. Because there is currently no specific treatment for genetic forms of ALS (outside clinical trials), it is certainly not the case that patients would not be interested in genetic testing. Quite the contrary might apply, and the apomediary and educated patient of today would like to know about every single aspect of his/her disease.
Given the relatively less favorable responses to survey items about doctors’ explanations of results and the results’ value to family members, as it emerged from the study, the authors suggest that patients could benefit from more extensive discussion of the complex issues surrounding transmission, penetrance, and testing of family members. They conclude that their findings support the practice of offering testing to all ALS patients.