Patients with Amyotrophic Lateral Sclerosis Have High Interest in and Limited Access to Genetic Testing
Electronic supplementary material
The online version of this article (doi:10.1007/s10897-016-0034-y) contains supplementary material, which is available to authorized users.
Abstract
Although genetic testing for amyotrophic lateral sclerosis (ALS) is widely available, it is unknown what proportion of patients with ALS have access to genetic counseling and testing, and patient attitudes towards ALS genetic testing have not been studied. We conducted a national survey of ALS patients enrolled in the Agency for Toxic Substances and Disease Registry, which consisted of multiple choice questions and two 12 item Likert scale series assessing respondents’ experience with and attitude toward genetic testing. The survey had an 8 % response rate, with 449 completed responses. Genetic testing was offered to 33.4 % and completed by 67.1 % of those offered. A minority of respondents (12.5 %) saw a genetic counselor, and were much more likely to be offered genetic testing (p = 0.0001). Respondents with a family history of ALS (8.4 %) were more likely to be offered testing (p = 0.0001) and complete testing (p = 0.05). Respondents with a family history of ALS were more likely to report a favorable attitude towards genetic testing (p = 0.0003), as were respondents who saw a genetic counselor (p = 0.02). The majority of respondents (82.7 %) felt that genetic testing should be offered to all patients with ALS. Our results indicate that ALS patients may have limited access to genetic testing, but perceive benefit from this service. Development of practice guidelines for genetic testing in ALS, to include the routine offer of genetic counseling, may result in broader and more consistent access to these services.
Introduction
Amyotrophic Lateral Sclerosis is an adult-onset neurodegenerative disorder characterized by loss of upper and lower motor neurons, progressive paralysis, and death within an average of 2–5 years after symptom onset. Symptom onset may be characterized as “limb onset” (beginning in an extremity) or “bulbar onset” (beginning with trouble speaking or swallowing). Diagnosis is based on clinical features, electrodiagnostic testing, and exclusion of other diseases with overlapping symptoms (Kinsley and Siddique 2015). Treatment is supportive and palliative, and there are currently no effective disease modifying therapies other than riluzole, which slows progression and prolongs survival by an average of 3 months (Rowland and Shneider 2001). While the majority of ALS cases appear to occur sporadically (sALS), approximately 5–10 % of ALS patients have a family history of the disease (fALS) (Gibson et al. 2014; Gros-Louis et al. 2006). Clinically, fALS and sALS are similar. However, fALS cases are distinguished by an earlier mean age of onset (46 years) than sALS cases (56 years) (Juneja et al. 1997; Testa et al. 2004).
The landscape of genetic counseling and testing ALS has been transformed in recent years with the identification of novel genes and the advent of next generation sequencing technology. The 2011 discovery of the hexanucleotide repeat expansion in C9orf72 led to the identification of pathogenic expansions in a significant percentage of both fALS and sALS, and revealed a common genetic etiology of some cases of ALS and frontotemporal dementia (FTD) (Renton et al. 2014). The genetic basis of two-thirds of familial ALS cases (fALS) and 10 % of sporadic ALS cases (sALS) has now been established (Renton et al. 2014). A relatively short time ago, genetic testing for ALS was limited to one gene (SOD1), with mutations in SOD1 accounting for 20 % of fALS. Current testing options now include assays for the C9orf72 repeat expansion, multigene next-generation sequencing panels, and whole exome sequencing.
Patients with ALS often ask why they developed the disease, what the chance is that they will pass it on to their children, and how quickly their condition will progress (Chiò et al. 2014). Detection of a specific genetic mutation underlying ALS may identify causality, allow accurate risk assessment and genetic testing of family members, and, in some cases, provide prognostic information regarding disease course. However, many fALS pedigrees demonstrate incomplete penetrance with high phenotypic variability, suggesting that additional genetic factors determine phenotype and could modify the disease course (Dols-Icardo et al. 2014). Some sALS and fALS pedigrees also harbor mutations in more than one gene, suggesting an oligogenic model of inheritance. In the future, treatments may be targeted toward patient genotype, as has already occurred in clinical trials for patients with SOD1 mutations (Miller et al. 2013) and potentially forthcoming for patients with C9orf72 hexanucleotide repeat expansions (Mendez and Sattler 2015).
It has been suggested that genetic advances have been slow to reach the clinical care of the ALS patient (Talbot 2014). No published data are available on patient access to and attitudes toward ALS genetic testing. In order to investigate patient perspectives and experience with ALS genetic testing, we conducted a survey of ALS patients enrolled in the Centers for Disease Control's Agency for Toxic Substance and Disease Registry. We examined factors associated with increased access to and positive attitude towards testing, and make suggestions for clinical practice. To our knowledge, this is the first study investigating patient access to and broadly exploring patient attitudes toward genetic testing in the ALS population. Data collected regarding patient experience with ALS genetic testing are reported separately.
Materials and Methods
This survey was conducted with approval from the Institutional Review Board at The Ohio State University, Columbus, Ohio.
Participants and Procedures
Eligible participants were identified and contacted through the Centers for Disease Control Agency for Toxic Substance and Disease Registry (CDC ATSDR). The CDC ATSDR advertised and distributed the survey link via a one-time email announcement, after approval from the ATSDR Committee. Reminder announcements were not permitted.
Study subjects completed an anonymous online survey using the survey engine SurveyMonkey®. Patients affected with ALS were eligible to participate. Family members and/or caregivers of affected individuals were also eligible to assist ALS patients in survey participation.
Instrumentation
The survey (See Supplementary Materials) included questions about demographic information, disease onset, family history, setting of clinical care, understanding of ALS genetics, and genetic testing and counseling offered. The survey utilized skip logic depending on answers regarding access to and outcome of genetic testing questions. Each survey track had approximately 20 questions and divided respondents into the following groups: 1) ALS patients who have not had genetic testing; 2) ALS patients who had genetic testing and received a result that was negative or inconclusive; 3) ALS patients who had genetic testing and received a result which was positive. Due to this tracking not all respondents were eligible to answer every question. The percentages and n's from this analysis reflect the number of participants who were eligible to answer and complete each question.
Two Likert scale questions assessed patient experience with (if applicable) and attitudes towards ALS genetic testing. The first Likert scale series question was completed only by respondents who had genetic testing, and assessed personal experience and feelings towards the process and outcome. The second Likert scale series question was completed by all respondents and assessed general attitudes towards genetic testing and its usefulness for patients, families, the medical community and society. Each Likert series item contained a 10-point scale, with responses ranging from “strongly agree” to “strongly disagree.” For analysis, responses were collapsed into three categories: agree, neutral and disagree.
Data Analysis
All results were tabulated and exported in .pdf, .ppt, .xcel, and/or .csv format for analysis. Data analysis was performed using JMP Version 11 software (SAS Institute, Cary, NC). Associations between groups and binary characteristics were studied using proportions and Fisher's exact test (see Table 1). A two-tailed p-value of 0.05 or less was considered significant.
| Offered genetic testing | Not offered genetic testing | |
|---|---|---|
| Diagnosis >50y (46) | 31.0 % | 69.0 % |
| Diagnosis <50y (263) | 44.6 % | 55.4 % |
| Prob>ChiSquare | ||
| 0.02 | ||
| Genetics explained/discussed | Genetics NOT explained/discussed | |
| positive family history of ALS (45) | 85.4 % | 14.6 % |
| negative family history of ALS (404) | 73.5 % | 26.5 % |
| Prob>ChiSquare | ||
| 0.06 | ||
| Genetic testing offered | Genetic testing NOT offered | |
| positive family history of ALS (45) | 68.9 % | 31.1 % |
| positive family history of dementia (155) | 39.4 % | 60.6 % |
| Prob>ChiSquare | ||
| 0.00001 | ||
| Genetic testing offered | Genetic testing NOT offered | |
| contact with GC (56) | 58.9 % | 41.1 % |
| no contact with GC (393) | 28.8 % | 71.2 % |
| Prob>ChiSquare | ||
| 0.00001 | ||
| Genetic testing positive attitude | Genetic testing negative attitude | |
| positive family history of ALS (45) | 75.6 % | 24.4 % |
| negative family history of ALS (404) | 54.0 % | 46.0 % |
| Prob>ChiSquare | ||
| 0.0003 | ||
| Genetic testing positive attitude | Genetic testing negative attitude | |
| contact with GC (56) | 75.0 % | 25.0 % |
| no contact with GC (393) | 53.2 % | 46.8 % |
| Prob>ChiSquare | ||
| 0.02 | ||
| Genetic testing positive attitude | Genetic testing negative attitude | |
| ALS genetic testing positive (21) | 85.7 % | 14.3 % |
| ALS genetic testing negative (55) | 80.0 % | 20.0 % |
| Prob>ChiSquare | ||
| 0.11 | ||
Results
Response Rate and Respondent Characteristics
The survey was emailed to 5,591 registrants; 449 responded (response rate = 8.0 %) and completed the survey. No respondents were excluded from data analysis.
The majority of respondents identified White/Caucasian ethnicity (95.3 %; n = 428/449) and age over 50 years (88.4 %; n = 397). Onset of ALS symptoms was indicated as limb in 77.7 % (n = 349) and bulbar in 22.2 % (n = 100). The majority of respondents (82.4 %; n = 370) indicated age at diagnosis as over age 50 years. Family history (first-degree, second-degree or other relative) was reported as positive for ALS in 10.0 % (n = 45/449); dementia (fronto-temporal dementia, Alzheimer disease or other dementia) in 34.5 % (n = 155/449), and Parkinson disease in 16.3 % (n = 73/449).
Setting Of Clinical Care and Providers Seen
The majority of respondents (79.5 %; n = 357) indicated they received care at a Muscular Dystrophy Association (MDA) and/or ALS Association (ALSA) certified center. Only 12.5 % (n = 56) of respondents indicated contact with a genetic counselor. Among respondents who reported a positive family history of ALS, 26.7 % (12/48) reported contact with a genetic counselor, compared to 10.5 % (47/449) of those who reported a negative family history (p = 0.0082).
Discussion and Understanding Of ALS Genetics
All respondents were asked if the genetics of ALS was discussed with or explained to them; 45.6 % (n = 205) indicated “discussed briefly,” 31.6 % (n = 142) indicated “explained,” and 22.7 % (n = 102) indicated “not discussed/don't remember.” Respondents who reported a family history of ALS were slightly more likely to also report that genetics was “explained” or at least “discussed briefly”, but this did not reach statistical significance (p = 0.08). The chance that an ALS patient's children could develop ALS was reported as “discussed briefly” by 15.3 % (n = 69) of all respondents. The majority of respondents indicated that ALS is “not usually/rarely/sometimes” genetic (84.4 %; n = 379), and 42.8 % (n = 192) indicted ALS is “not usually/rarely/sometimes” familial. Almost half of respondents (49.9 %; n = 224) did not know that genetic testing for ALS is available, or indicated it was never available. Half of respondents (53.0 %; n = 238/449) did not know whether genetic testing is available for family members of ALS patients, or indicated it was never available (see Table 2).
| Never | Not usually/ Rarely/Sometimes | Most of the time/Always | Don't know | |
|---|---|---|---|---|
| Is ALS Genetic? | 4.4 % (20) | 76.7 % (344) | 3.5 % (16) | 15.4 % (69) |
| How often is ALS familial? | 0.4 % (2) | 96.3 % (432) | 3.3 % (15) | – |
| Is genetic testing available for ALS patients? | 5.0 % (22) | 28.9 % (130) | 29.7 % (134) | 36.4 % (163) |
| Is genetic testing available for families of ALS patients? | 5.0 % (22) | 30.0 % (135) | 20.1 % (90) | 44.9 % (202) |
Access to Genetic Testing and Understanding of Results
Genetic testing was offered to 34.7 % (n = 156) of respondents and completed in 67.3 % (n = 105) of those offered. Clinical genetic testing was undertaken by 47.6 % (n = 50). Research genetic testing was performed in 29.5 % (n = 31), and 22.9 % (n = 24) of respondents were “not sure” if genetic testing was clinical or research. Only 22.9 % (n = 103) of all respondents requested information about genetic testing. Respondents with a family history of ALS were more likely to be offered genetic testing than respondents who reported a family history of dementia (p = 0.00001). Respondents who indicated a young age of onset (diagnosis before age 50 years) were also more likely to be offered genetic testing than those who reported age of onset and diagnosis of over 50 years (p = 0.02). Once offered, genetic testing was more likely to be completed in those who reported a family history of ALS (p = 0.05), with 55.6 % (25/45) of respondents who reported a family history of ALS accepting testing, versus 19.5 % (79/404) of those with a negative family history. A minority of all respondents (12.5 %; n = 56) indicated contact a genetic counselor, and they were much more likely to be offered genetic testing (p = 0.00001). Six respondents reported that family members were offered pre-symptomatic testing; of these, only one saw a genetic counselor.
Of the 156 respondents who reported undergoing genetic testing, 85 indicated they were informed of their results. Test result was reported as negative in 53 (62.4 %), positive in 23 (27.1 %), inconclusive in 3 (3.5 %), and 6 (7.1 %) reported “don't remember.” Fifteen respondents recalled testing positive for C9orf72, five for SOD1, while three could not recall which gene. In ALS patients who reported a pathogenic C9orf72 mutation, 10/15 (66.7 %) also reported a positive family history. In ALS patients who reported a pathogenic SOD1 mutation, 100 % (5/5) also reported a positive family history. Among the six respondents who reported that family members were offered pre-symptomatic testing, three indicated that family members underwent testing.
Of the 51 respondents who reported being offered genetic testing, but elected to not undergo testing, 52.0 % indicated cost was the main detractor. Other reasons included: “Do not believe that ALS is running in the family” (40.0 %); “Concerned about burdening my family members” (22.0 %) “Do not wish to know if ALS is running in the family” (16.0 %); “Concerned about ability to obtain insurance coverage if tested” (14.0 %). Respondents were allowed to choose more than one concern.
The 85 respondents who indicated they underwent genetic testing and were informed of their results were asked to indicate how results were disclosed and by whom; multiple selections were permitted. Genetic testing results were reported as disclosed most often by a physician (69.4 %), followed by genetic counselor (25.9 %), “other” (8.2 %), nurse (5.9 %), and nurse practitioner (4.7 %). Test results were most often disclosed during an office visit (65.1 %) or by letter (37.4 %), while 16.9 % reported results disclosure via telephone. Among respondents who underwent genetic testing and a mutation was found, 65.0 % (13/20) indicated an understanding of the typical autosomal dominant inheritance of ALS mutations, and recalled discussing the chance that their children could also develop ALS. Over half of those completing testing (56.5 %; n = 13/23) recalled that a doctor/team member discussed the likelihood of a gene carrier developing ALS (i.e. the concept of variable penetrance).
Attitudes Toward Genetic Testing
Data from a 12-item Likert scale assessing attitudes towards ALS genetic testing from all 450 completed surveys revealed that respondents had generally positive attitudes towards genetic testing and its usefulness for ALS patients, families, the medical community and society (see Table 3). A majority of respondents agreed that genetic testing should be offered to any patient with ALS (82.6 %; n = 372) and to patients with a family history of ALS (94.1 %; n = 423), with 77.5 % (n = 348) of respondents indicating they would have genetic testing if offered. Most perceived benefit to the medical community and society, agreeing that genetic testing can help doctors understand ALS (77.7 %; n = 348), and treat ALS in the future (86.0 %; n = 386), and that, for society, the pros of ALS genetic testing outweigh the cons (77.1 %; n = 347).
| Question | Agree | Neutral | Disagree | Does not apply |
|---|---|---|---|---|
| Genetic testing should be offered to patients with ALS | 82.7 % (371) | 14.4 % (65) | 2.2 % (10) | 0.7 % (3) |
| Genetic testing should be offered to patients with ALS who have a family history of ALS | 94.0 % (422) | 4.9 % (22) | 0.7 % (3) | 0.4 % (2) |
| Genetic testing can provide useful information to patients with ALS | 80.2 % (360) | 17.1 % (77) | 2.0 % (9) | 0.7 % (3) |
| Genetic testing should be offered to family members of persons with ALS | 82.1 % (368) | 15.3 % (69) | 2.2 % (10) | 0.4 % (2) |
| Genetic testing should be offered to family members of persons with ALS who have a gene mutation | 87.8 % (394) | 10.0 % (45) | 1.3 % (6) | 0.9 % (4) |
| Genetic testing can provide useful information to family members of persons with ALS | 81.7 % (366) | 16.3 % (74) | 1.3 % (6) | 0.7 % (3) |
| If I were offered genetic testing for ALS, I would have genetic testing | 77.5 % (348) | 14.3 % (64) | 5.3 % (24) | 2.9 % (13) |
| If my adult children wanted genetic testing for ALS, I would support them | 85.6 % (384) | 5.6 % (25) | 0.7 % (3) | 8.2 % (37) |
| Genetic testing can help doctors understand my condition | 77.6 % (349) | 19.0 % (85) | 2.7 % (12) | 0.7 % (3) |
| In the future, genetic testing may help doctors treat ALS | 86.0 % (386) | 12.2 % (55) | 1.1 % (5) | 0.7 % (3) |
| For me, the pros of genetic testing for ALS outweigh the cons | 75.9 % (341) | 20.3 % (91) | 3.1 % (14) | 0.7 % (3) |
| For society, the pros of genetic testing for ALS outweigh the cons | 77.1 % (346) | 19.5 % (88) | 2.7 % (12) | 0.7 % (3) |
- Agree = “Strongly Agree,” “Agree,” “Somewhat Agree.” Neutral = “Maybe Agree,” “Neutral,” “Maybe Disagree.” Disagree = “”Somewhat Disagree,” “Disagree,” “Strongly Disagree.” Respondents who chose “Does Not Apply” are reported separate of the other responses
In order to compare overall genetic testing attitudes between groups, respondents with combined “Agree” (includes “Strongly Agree,” “Agree,” and “Somewhat Agree”) responses to all twelve Likert scale items were compared to those that chose “Neutral” (“Maybe Agree,” “Neutral,” and “Maybe Disagree”) and “Disagree” (“Somewhat Disagree,” “Disagree” and “Strongly Disagree”) for one or more of the items (see Table 1). Respondents with a family history of ALS were more likely to report a favorable attitude towards genetic testing (p = 0.0003) than were those without a family history, as were respondents who saw a genetic counselor (p = 0.02) compared to those who did not see a genetic counselor. No significant difference in attitudes were observed between those who tested positive or negative (p = 0.11). Among those who tested positive, 20/20 (100 %) indicated “agree/strongly agree” in response to the items “For me, the pros of genetic testing for ALS outweigh the cons” and “For society, the pros of genetic testing for ALS outweigh the cons.”
Discussion
These data suggest that the majority of ALS patients have a favorable attitude towards genetic testing and feel that genetic testing should be available to all patients. However, only about 1/3 (34.7 %) of survey respondents reported being offered genetic testing. A positive family history of ALS is, in practice, strongly correlated with the offer of genetic testing. Interestingly, however, the majority of those offered testing did not have a family history. Therefore, of all respondents who were offered genetic testing, only 9 % (n = 14) reported a positive family history. As such, these data suggest that the clinical approach to the offer of genetic testing in ALS may be inconsistent. Other factors positively associated with the offer of genetic testing included young age at onset (p = 0.02) and seeing a genetic counselor (p = 0.0001). Only 12.5 % reported seeing a genetic counselor; among those with a positive family history of ALS (fALS), this proportion was somewhat higher (25.0 %).
It appears that most ALS patients have a basic understanding of the hereditary component of ALS, but opportunities for improvement in education are apparent. The majority of respondents reported that the genetics of ALS was discussed with them during the course of their care, and most indicated understanding that ALS is only sometimes genetic or familial. However, only about half of respondents recalled discussing the risk that children could develop ALS, and half did not know genetic testing was available. Among those who underwent testing, roughly half indicated understanding of dominant transmission, and 50 % recalled discussing the issue of variable penetrance. More extensive discussion of the availability of genetic testing, risk to family members, and variable penetrance may help patients understand the implications of their diagnosis for family members.
Survey respondents indicated a favorable attitude towards genetic testing and perceived benefits to ALS patients, families, the medical community, and society. This was most pronounced in respondents who reported a positive family history of ALS, and in those who saw a genetic counselor. Interestingly, there was no difference in test attitude scores in those who tested positive compared to those who tested negative. Although we did not attempt to measure psychological harm associated with testing positive, these findings suggest that those who get “bad news” maintain a favorable outlook about the benefits of testing.
In a survey of patients with Parkinson disease, Falcone et al. (Falcone et al. 2011) similarly found a high level of interest in genetic testing, with 86 % indicating that genetic testing is useful, and 59 % indicating interest in genetic testing. Although most respondents were found to have a low level of genetic knowledge and poor awareness of genetic testing, most perceived benefits from genetic testing including development of better treatments. The authors concluded that there is “considerable need for genetics education and counseling in the PD population” (p. 394). Our results suggest a similar need in the ALS population.
In the only previously published study on attitudes toward genetic testing in ALS that we could identify, Fanos et al. (Fanos et al. 2004) surveyed and interviewed family members of ALS patients regarding their attitudes towards presymptomatic testing. They found that 60 % of respondents said that they would have presymptomatic testing if offered, 24 % understood the inheritance of familial ALS, and 64 % were aware that not all gene carriers would develop symptoms. We also identified a positive attitude towards presymptomatic testing in our respondents affected with ALS, with 82.1 % agreeing that genetic testing should be offered to family members of persons with ALS. Despite the positive attitude towards genetic testing, Fanos et al. identified evidence of confusion regarding genetic testing, such as the implication of a negative test result in a family member affected with fALS. They concluded with the recommendation that consensus guidelines for fALS genetic counseling and testing be developed.
Although there are no current published practice guidelines for genetic counseling or genetic testing in ALS, several recent publications approach or address this issue. Fong et al. (Fong et al. 2012) state that persons who wish to learn the potential cause of ALS in their family “should be offered genetic counseling, irrespective of but especially in the presence of a suggestive family history” (p. 30) and discuss genetic testing, but do not indicate specific guidelines. Chiò et al. (Chiò et al. 2014) recommend that genetic testing be offered to those with fALS (specifically, a first and/or second-degree relative). They also recommend that “multidisciplinary counselling that addresses all relevant issues, including disclosure of test results to family members and the risk for genetic discrimination (p. 478).” Roggenbuck et al. (Roggenbuck et al. 2016) propose that genetic counseling and the offer of testing be included in the routine management of ALS, and outline a testing approach including the offer of C9orf72 repeat expansion testing to all ALS patients of European descent. The publication of ALS genetic counseling and testing practice guidelines, similar to those for Alzheimer disease (Goldman et al. 2011), would represent a significant step towards broader and more consistent access to genetic counseling and testing in ALS.
Study Limitations
This survey was sent to registrants as a one-time announcement per CDC ATSDR protocol; repeat announcements of this survey not allowed. A previous publication utilizing the registry for survey distribution received a similar response rate of 11.5 % (Kullmann et al. 2015). The low response rate could bias study data if respondents were not representative of the general ALS patient population. However, respondent demographic and disease characteristics mirror those reported in ALS population as a whole (Mehta et al. 2014). This survey was sent via email distribution by the United States (U.S.) National ALS Registry, which is curated by the Agency for Toxic Substances and Disease Registry at the U.S. Centers for Disease Control. It is the only U.S. National ALS Registry to date, and may not be representative of the entire ALS patient population. However, due to the far-reaching nature of the Registry, the authors deemed it was the most appropriate avenue for access to as many ALS patients as possible, therefore allowing a large-spectrum, nationwide survey to be as representative as possible.
All data were analyzed on the assumption that the survey responses were collected from ALS patients or caregivers acting on behalf of the patient, and no methods were set up to differentiate between these two groups. The survey stated that caregivers were allowed to assist patients in their responses, since the disabilities associated with advanced ALS could be a barrier to independent survey participation. It was a goal of the authors to include as many ALS patients as were able to participate, despite potential physical limitations, therefore potentially reducing ascertainment bias of patients whose disease course was not advanced or advancing slowly. Responses relied on patient recall of discussions by healthcare providers and the healthcare provider “genetic counselor” was not defined as a masters-trained clinician. Numerous univariate tests were performed without correction for family-wise error rate, and a number of statistically significant findings may be due to chance alone. However, due to the exploratory nature of this research, as less stringent p value was utilized during data analysis.
This survey was distributed electronically to only those ALS patients registered with the CDC; ATSDR registry, which is introduced to patients receiving care at a certified MDA or ALSA treatment center, which is a minority of all ALS patients (Mehta et al. 2014). Our results could reflect an ascertainment bias of a skewed population of ALS patients who are actively engaged with research participation and potentially more receptive to new technologies such as genetic testing. If our survey reached a broader spectrum of ALS patients in all care settings, patient attitudes toward genetic testing may have been less positive.
Practice Implications
These data suggest that a majority of ALS patients have a favorable attitude towards genetic testing, and feel that it should be available to all patients. However, only about 1/3 of survey respondents reported being offered testing. Development of practice guidelines for genetic testing in ALS, to include the routine offer of genetic counseling, may result in broader and more consistent access to this service. ALS genetic testing should be offered in the context of genetic counseling protocol and results disclosed by trained personnel. As the genetics of ALS continues to be elucidated and translated into advances in clinical care, there will be an increasing need to incorporate genetic testing and counseling into the management of ALS.
Research Recommendations
Further research is needed to study the impact of genetic testing in ALS. Our data suggest that ALS patients generally have a favorable attitude towards testing, but further exploration of specific subgroups may inform genetic testing and counseling in challenging cases, such as those patients who receive inconclusive results, those with a positive family history who test negative, and those who with a negative family history who test positive.
Below is the link to the electronic supplementary material.
Compliance with Ethical Standards
Ethical Statement
Funding for this project was provided by the National Society of Genetic Counselors Neurogenetics Special Interest Group.
Conflict of Interest
Authors Wagner, Nagaraja, Allain, Quick, Kolb and Roggenbuck declare they have no conflict of interest.
Human Studies and Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.
Animal Studies
No animal studies were carried out by the authors for this article.
