Genetic testing for amyotrophic lateral sclerosis in Canada – an assessment of current practices

Abstract

Objective: To understand current genetic testing practices at Canadian ALS clinics. Methods: An online survey and phone interviews, with clinicians practicing in 27 ALS clinics in Canada, were employed to collect data. Quantitative and qualitative analyses were conducted. Results: Ninety-three percent (25/27) of ALS clinics in Canada are routinely ordering genetic testing for familial ALS, while 33% (9/27) of clinics are routinely ordering genetic testing for sporadic ALS. Barriers to genetic testing include a perceived lack of an impact on treatment plan, difficulty in obtaining approvals, primarily from provincial Ministries of Health, and limited access to genetic counseling. Predictive testing practices were found to be the most variable across the country. The average wait time for a symptomatic patient living with ALS to see a genetic counselor in Canada is 10 months (range 0-36 months). Conclusions: Access to genetic testing, and testing practices, vary greatly across Canadian ALS clinics. There may be patients with a monogenetic etiology to their ALS who are not being identified given that genetic testing for patients diagnosed with ALS is not routinely performed at all clinics. This study highlights potential inequities for patients with ALS that can arise from variability in health care delivery across jurisdictions, in a federally-funded, but provincially-regulated, health care system. Clinical trials for both symptomatic ALS patients and pre-symptomatic ALS gene carriers are ongoing, and ALS clinicians in Canada are motivated to improve access to genetic testing for ALS.

Clinical testing panels for ALS: global distribution, consistency, and challenges

“…A 2017 survey of 167 clinicians from 21 countries found that over 90% of respondents would offer genetic testing to their fALS patients, and 49% of respondents would offer genetic testing to their sALS patients (13), with similar results being obtained from a 2021 Canadian study (8). However, both studies also found a lack of consensus regarding which ALS patients should be eligible for genetic testing and the testing practices that should be used (8, 13).…”

“…Patient interest and the potential for impact on clinical care has resulted in an increase in the number of clinicians utilizing genetic testing for their ALS patients. A 2017 survey of 167 clinicians from 21 countries found that over 90% of respondents would offer genetic testing to their fALS patients, and 49% of respondents would offer genetic testing to their sALS patients (13), with similar results being obtained from a 2021 Canadian study (8).…”

“…Our analysis shows that a group of core genes are represented on most panels — over 90% of the clinical panels included sequencing of the genes ANG, FUS, OPTN, SETX, SOD1, TARDBP, UBQLN2, VAPB , and VCP . Further, a recent assessment of Canadian clinics offering genetic testing for fALS cases found that a substantial subset (36%) are only ordering tests for SOD1 and the C9orf72 GGGGCC HRE (8), likely resulting in a large number of false negative genetic results from the failure to assess other genes with a definitive relationship with ALS.…”

“…However, genetic testing can end the diagnostic odyssey many patients experience, and there is particular interest in genetic testing due to the increasing number of clinical trials enrolling specific genetic populations (7). Ongoing trials include those for symptomatic ALS patients carrying pathogenic variants in ATXN2, C9orf72, FUS , and SOD1 (NCT04494256, NCT03626012, NCT04931862, NCT04768972, NCT02623699, NCT05039099) (8). A recent prospective assessment of genetic testing in an ALS referral clinic suggested that routine screening for pathogenic variants in ALS patients may impact clinical care in at least 21% of cases (9).…”

Genetic counseling and diagnostic genetic testing for familial amyotrophic lateral sclerosis and/or frontotemporal dementia: A qualitative study of client experiences

“…Flexible approaches that adapt the pre‐and post‐test counseling to the client’s needs, take into account individual circumstances, and work to ensure the best possible outcome for both the person with the disease and their family are key (Craufurd et al, 2015). Genetic counselors are well equipped to provide client‐ and family‐centered genetic counseling regarding diagnostic testing, but clinical genetics health professionals are not always a part of multidisciplinary ALS/MND/FTD care, and timely access may be difficult (Salmon et al, 2021). Regardless of the health professional type who facilitates genetic counseling and diagnostic testing discussions, avenues to access more information and support outside of formal genetic counseling or testing discussions could be helpful as not all clients will require the same amount of information and support pre‐and post‐testing (Crook et al, 2021).…”