Genetic testing in ALS: A survey of current practices

Abstract

Objective: To determine the degree of consensus among clinicians on the clinical use of genetic testing in amyotrophic lateral sclerosis (ALS) and the factors that determine decision-making.

Methods: ALS researchers worldwide were invited to participate in a detailed online survey to determine their attitudes and practices relating to genetic testing.

Results: Responses from 167 clinicians from 21 different countries were analyzed. The majority of respondents (73.3%) do not consider that there is a consensus definition of familial ALS (FALS). Fifty-seven percent consider a family history of frontotemporal dementia and 48.5% the presence of a known ALS genetic mutation as sufficient for a diagnosis of FALS. Most respondents (90.2%) offer genetic testing to patients they define as having FALS and 49.4% to patients with sporadic ALS. Four main genes (SOD1, C9orf72, TARDBP, and FUS) are commonly tested. A total of 55.2% of respondents would seek genetic testing if they had personally received a diagnosis of ALS. Forty-two percent never offer presymptomatic testing to family members of patients with FALS. Responses varied between ALS specialists and nonspecialists and based on the number of new patients seen per year.

Conclusions: There is a lack of consensus among clinicians as to the definition of FALS. Substantial variation exists in attitude and practices related to genetic testing of patients and presymptomatic testing of their relatives across geographic regions and between experienced specialists in ALS and nonspecialists.

Figure 1. Definition of familial amyotrophic lateral sclerosis (FALS)

(A) Country-specific variation in opinion on the existence of a standard definition for FALS. (B) FALS definitions used by respondents. Within amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) disease categories, choice of a lower-stringency definition automatically meant higher stringency definitions were also selected. SALS = sporadic amyotrophic lateral sclerosis.

Figure 2. Genetic testing of patients with and without a family history of amyotrophic lateral sclerosis (ALS)

(A) Diagnostic genetic testing offered to patients with a family history of ALS (yes/no). (B) Diagnostic genetic testing offered to patients with no known family history of ALS (yes/no). (C) Genetic testing recommended to indicated proband (yes/no).

Figure 3. Choice of genes in genetic testing

(A) Heat map of genes tested by respondents broken down by country. (B) The number of publications in amyotrophic lateral sclerosis (ALS) research concerning each gene as a function of the number of respondents who test for that gene (top) and the number of mutations reported in the ALS online database (ALSoD) for each gene as a function of the number of respondents who test for that gene (bottom).

Figure 4. Number of respondents who would seek genetic testing if diagnosed with amyotrophic lateral sclerosis (ALS)

(A) Would seek genetic testing (yes/no). (B) Would seek genetic testing if the indicated proband (yes/no).

Figure 5. Respondents' opinions on presymptomatic testing

(A) Would offer presymptomatic testing to family members of patients with known (FALS) (yes/no). (B) Factors that would determine the decision to offer presymptomatic testing to family members of patients with known familial amyotrophic lateral sclerosis (FALS).