Patients with sporadic and familial amyotrophic lateral sclerosis found value in genetic testing

Wagner, Karin; Nagaraja, Haikady N.; Allain, Dawn C.; Quick, Adam; Kolb, Stephen J.; Roggenbuck, Jennifer

doi:10.1002/mgg3.360

Cited by 18 publications

(35 citation statements)

References 17 publications

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“…The survey gathered information regarding genetic testing and counselling practices, as well as clinician attitudes and other factors that may be associated with the offer of genetic testing. In addition, we compared clinician attitudes towards genetic testing to attitudes of persons with ALS, which we have previously reported (7). The findings of this study may inform the development of consensus practice guidelines for ALS genetic testing and counselling, which may in turn enable more consistent patient access to genetic information, risk assessment, and, in the future, targeted treatment options for persons with ALS.…”

Section: Introductionmentioning

confidence: 93%

Lack of consensus in ALS genetic testing practices and divergent views between ALS clinicians and patients

Klepek

Nagaraja

Goutman

et al. 2019

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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Recent advances in ALS gene discovery have both empowered and challenged clinicians providing evaluation and care for persons with ALS, many of whom seek an answer as to the cause of their condition. In order to study clinician practices and attitudes towards genetic testing, we surveyed members of the Northeast ALS Consortium, an international group of specialist ALS clinicians; responses were received from 80/255 (response rate = 31.4%). While 92.3% indicated they offered genetic testing to patients with familial ALS, 57.0% offered testing to patients with ALS and a family history of dementia, and 36.9% offered testing to patients with sporadic ALS, revealing a lack of consensus with respect to the approach to the typical ALS patient encountered in clinical practice. In addition, comparison of clinician and patient attitudes towards genetic testing revealed that clinicians valued the scientific potential of testing, but were less likely to say they would have testing themselves, or to see the value in testing for family members. People with ALS were more likely to see value of testing for themselves and for family members, and less likely to strongly value the scientific potential of testing.

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Section: Introductionmentioning

confidence: 93%

Lack of consensus in ALS genetic testing practices and divergent views between ALS clinicians and patients

Klepek

Nagaraja

Goutman

et al. 2019

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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“…Among those who had testing, those who received positive and negative results reported equally favorable experiences, suggesting that those who get "bad news" maintained a favorable outlook about the benefits of testing. 18,19 Attitudes toward presymptomatic ALS testing have also been studied; in a study of family members of persons with ALS, 60% indicated they would have presymptomatic testing if offered. 20 Challenges in Laboratory Detection and Interpretation of the HRE PCR-based assays for detection of the HRE are widely used in commercial laboratories, but their accuracy has been questioned.…”

Section: Current Status Of Testing and Counselingmentioning

confidence: 99%

C9orf72 and the Care of the Patient With ALS or FTD

Roggenbuck

2021

Neurol Genet

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The 2011 discovery of the pathogenic hexanucleotide repeat expansion (HRE) in C9orf72, the leading genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), marked a breakthrough in the effort to unravel the etiology of these conditions. Ten years later, clinicians are still working to integrate the implications of this discovery into the care of individuals with ALS and/or FTD. Consensus management guidelines for ALS do not comprehensively address the issue of genetic testing, and questions remain about whom to test, what counseling should be provided before and after testing, laboratory methods, and test interpretation. These challenges have contributed to inconsistent clinical practices and present barriers to patients wishing to access testing. This review summarizes the clinical impact of the discovery of the C9orf72 HRE, outlines ongoing challenges, and provides recommendations for C9orf72 testing, counseling, and research.

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“…Indeed, a genetic cause in seemingly sporadic ALS can be masked by recessive inheritance, reduced penetrance, small family size, lack of family information, and illegitimacy. Within the last few years, neurologists started offering genetic counseling to ALS patients more frequently and patients who underwent genetic counseling reported a positive experience and found value in testing [ 41 ]. According to the guidelines of the German Society of Neurology, genetic testing should be offered to patients with familial ALS, patients who have family members with dementia, and patients with an early onset and rapid progression [ 28 ].…”

Section: Genetic Testing and Counselingmentioning

confidence: 99%

Current knowledge and recent insights into the genetic basis of amyotrophic lateral sclerosis

Volk

Weishaupt

Andersen

et al. 2018

Medizinische Genetik

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Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease, affecting the upper and/or lower motor neurons. However, extramotor symptoms can also occur; cognitive deficits are present in more than 40% of patients and 5–8% of ALS patients develop frontotemporal dementia. There is no effective treatment for ALS and median survival is 2–3 years after onset.Amyotrophic lateral sclerosis is a genetically heterogeneous disorder with monogenic forms as well as complex genetic etiology. Currently, complex genetic risk factors are of minor interest for routine diagnostic testing or counseling of patients and their families. By contrast, a monogenic cause can be identified in 70% of familial and 10% of sporadic ALS cases. The most frequent genetic cause is a noncoding hexanucleotide repeat expansion in the C9orf72 gene. In recent years, high-throughput sequencing technologies have helped to identify additional monogenic and complex risk factors of ALS.Genetic counseling should be offered to all ALS patients and their first- and possibly second-degree relatives, and should include information about the possibilities and limitations of genetic testing. Routine diagnostic testing should at least encompass the most frequently mutated disease genes (C9orf72, SOD1, TDP-43, FUS). Targeted sequencing approaches including further disease genes may be applied. Caution is warranted as the C9orf72 repeat expansion cannot be detected by routine sequencing technologies and testing by polymerase chain reaction (PCR) is failure-prone.Predictive testing is possible in families in which a genetic cause has been identified, but the limitations of genetic testing (i. e., the problems of incomplete penetrance, variable expressivity and possible oligogenic inheritance) have to be explained to the families.

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Patients with sporadic and familial amyotrophic lateral sclerosis found value in genetic testing

Cited by 18 publications

References 17 publications

Lack of consensus in ALS genetic testing practices and divergent views between ALS clinicians and patients

Lack of consensus in ALS genetic testing practices and divergent views between ALS clinicians and patients

C9orf72 and the Care of the Patient With ALS or FTD

Current knowledge and recent insights into the genetic basis of amyotrophic lateral sclerosis

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