Only a minority of amyotrophic lateral sclerosis (ALS) patients are concerned about a possible negative impact of genetic testing on their well-being and that of their family, according to the results of a small survey in the Chicago area.
The survey’s findings, presented in a poster session at the 2019 American Academy of Neurology (AAN) Annual Meeting, ending today in Philadelphia, further showed that genetic testing is useful in the diagnosis of ALS and frontotemporal dementia (FTD), regardless of the patients’ family history of these diseases.
With over 100 genes associated with ALS, genetic testing plays a key role in determining both the risk for this disease and the eligibility of patients for clinical trials for familial ALS.
The study, “A Survey of Attitudes Towards Genetic Testing in Amyotrophic Lateral Sclerosis (ALS),” was designed to identify the psychological, social, ethical, and legal implications of genetic testing for this disease.
A team from the National Human Genome Research Institute, the University of Chicago Medical Center, and the ALS Association administered a survey to 40 patients from the Chicago metropolitan area, with questions about demographics, family history, attitudes toward genetic testing, genetic counseling, and end-of-life options. Participants responded to all or part of the survey.
None of the participants had known family history of ALS. The patients were mostly male, Catholic, Caucasian, and had been diagnosed for more than a year.
Almost all had heard about genetic testing, and the majority had discussed its risks and benefits with their physician. Helping to find a cure for ALS was the factor with the greatest influence on whether to accept genetic testing. A small subset of patients expressed concerns about genetic testing having a possible negative impact on their, or their family’s, emotional well-being. Asked about choosing different interventions, a higher proportion of participants said they were more likely to opt for non-invasive ventilation (BiPAP) and palliative care, as opposed to cardiopulmonary resuscitation (CPR)and tracheostomy (breathing tube for ventilation).
Most patients reported adequate access to psychiatric or psychological care. Only a small minority answered a question about physician-assisted suicide, which, according to the scientists, suggests that this “is an emotionally impactful issue for ALS patients.”
Further studies are planned to explore whether these findings are confirmed in larger regional and national groups, the researchers said.
In turn, the research, “Genetic Testing Has a High Diagnostic Yield for Individuals with ALS regardless of Family History,” aimed at evaluating the impact of family history on the diagnostic rates of a key repeat expansion in the C9orf72 gene and on the sequencing of 24 ALS genes. The C9orf72 gene provides instructions for making a protein found in various tissues.
The most common genetic cause of familial and sporadic ALS and FTD — found in a substantial number of ALS patients — is an expanded GGGGCC repeat, which means four guanine (G) followed by two cytosine (C) nucleotides in the first intron of C9orf72. Nucleotides are the building blocks of DNA, while introns are DNA bits normally taken out in protein production.
The study included 347 participants with an average age of 59 (range 21-92 years) and clinical suspicion of ALS or FTD. A total 166 participants reported family history of ALS or FTD.
Repeat expansions in C9orf72 were detected in 20.5% of the 293 participants undergoing testing for this specific sequence. They also were detected in 26.6% of the 139 participants with family history of these diseases, and in 14.9% of the 154 without such family history.
These results suggest that analysis of C9orf72 repeat expansions “should be considered in all individuals,” the scientists said.
Researchers then conducted sequencing of the 24 ALS genes in 180 participants, including 116 without C9orf72 repeat expansions. The results were positive for 13 participants (7.2%) — nine of the 78 with known family history of ALS or FTD, and four of the 102 (3.9%) without such history.
There were markedly lower detection percentages with multi-gene sequencing than with C9orf72 analysis.
“This is possibly due to the later age of onset and reduced prevalence of the disorders associated with the genes on the multi-gene panel vs. C9orf72,” the poster read.
“Ultimately, this work shows that genetic testing has diagnostic utility for individuals with ALS/FTD regardless of family history,” the study concluded.