[State of knowledge: amyotrophic lateral sclerosis with or without frontotemporal dementia NGS panel]
Gravel C, Bélanger S
Record ID 32018002305
Original Title: Panel de la sclérose latérale amyotrophique avec ou sans démence frontotemporale par SNG: rapport d’évaluation sur le rapatriement d’analyses réalisées hors Québec
Authors' objectives: At the MSSS’s request, the Institut national d’excellence en santé et en services sociaux (INESSS) is conducting a rapid assessment of the relevance, the issues and, when appropriate, the optimal implementation mechanisms concerning the repatriation of these tests, this from the overall perspective of Québec’s health-care system. This report deals specifically with the analysis of NGS gene panels for the molecular diagnosis of amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD).
Authors' results and conclusions: RESULTS: -CLINICAL CONTEXTS AND PROPOSED TESTS: ALS and FTD are progressive neurodegenerative diseases with fatal outcomes. They usually develop in adulthood and share important clinical, pathological and genetic features. Approximately 10% of ALS cases and 40% of FTD cases are familial. To identify the genetic abnormality potentially responsible for ALS/FTD (genotype-phenotype correlation) and thus guide the management of affected individuals and their families, the V requester is proposing the launch of an offer of services for a two-step molecular diagnosis. The first step consists in analyzing the genes with a higher diagnostic yield or for which clinical studies are underway (C9orf72, ATXN2, SOD1, FUS and TARDBP). The second step is a virtual panel of 22 ALS/FTD genes analyzed from exome sequencing data. This step will be offered only in familial or early cases when the result of the analysis of the main targets is negative. -CLINICAL VALIDITY: The choice of genes to be analyzed was based on the literature and the PanelApp resource (Genomics England, UK). Based on the available data, the diagnostic yield of the main target analysis (step 1) ranges from 13% to 28% for sporadic forms and from 63% to 82% for familial or early forms of SLA/DFT. The diagnostic yield of the 22-gene panel is not known. (CLINICAL UTILITY): Confirmation of a genetic etiology through molecular investigations permits access to clinical studies, provides information on the prognosis and natural history of the disease, guides genetic counselling and enables one to offer predictive testing to relatives. Genetic analysis also enables affected individuals to make informed decisions about various aspects of their lives, such as career, family planning, palliative care, and lifestyle. -IMPLEMENTATION CONSIDERATIONS: Information from both the literature and the expert consultations indicate that molecular investigations of ALS/FTD should be prioritized on the basis of a combination of clinical presentation and family history data. In this regard, to support the rollout of this offer of service, a clinical algorithm is presented. A neurology or medical genetics consultation and the application of clinical and paraclinical criteria are prerequisites for molecular testing. In light of the consultations held, even if the offer of molecular diagnostic services for this disease generally appears to be in line with patients’ needs, some concerns regarding the sequence of testing and how it will be performed in Quebec were highlighted and should be explored to ensure the relevance and optimal implementation of the service offered. -ECONOMIC ANALYSIS: No economic studies transposable to the Québec context were found. INESSS is therefore not in a position to rule on the efficiency of gene panel analysis to establish the molecular diagnosis of ALS/FTD by NGS in clinical settings. CONCLUSION: Findings and conclusions in this report are based on a rapid review of the scientific and grey literature and on contextual data and experiential knowledge. The approach consists of a rapid risk analysis to guide the ministerial decisions regarding the repatriation and implementation of tests for the molecular diagnosis of ALS/FTD. During this exercise, no significant concerns were raised, and the information gathered supports the relevance of repatriating these tests. However, uncertainties regarding the sequence of testing and how it will be performed in Québec were raised and should be investigated to ensure these tests’ relevance and optimal implementation. As well, the conclusions concerning the potential savings indicated in this report should be viewed with caution.
Authors' methods: The process included a rapid review of the scientific and grey literature regarding the clinical and economic aspects, a budget impact analysis, and consultations with Québec experts. Only documents containing synthesis data or recommendations concerning the use of an NGS test for the molecular diagnosis of amyotrophic lateral sclerosis with or without frontotemporal dementia (ALS/FTD) were selected. INESSS set up an advisory committee, whose members were invited to express their views on the different implementation issues and aspects regarding the repatriation of the proposed tests. The final findings are based on the triangulation of the scientific data, the positions of the main learned societies consulted, and the contextual data and experiential knowledge that had been gathered.
Project Status: Completed
URL for project: https://www.inesss.qc.ca/fileadmin/doc/INESSS/Rapports/Biologie_medicale/INESSS_SLA_EC.pdf
Year Published: 2022
URL for published report: https://www.inesss.qc.ca/fileadmin/doc/INESSS/Rapports/Biologie_medicale/INESSS_SLA_EC.pdf
English language abstract: An English language summary is available
Publication Type: Other
- Costs and Cost Analysis
- Genetic Testing
- Frontotemporal Dementia
- High-Throughput Nucleotide Sequencing
- Amyotrophic Lateral Sclerosis
Organisation Name: Institut national d'excellence en sante et en services sociaux
Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369
Contact Name: email@example.com
Contact Email: firstname.lastname@example.org
Copyright: Gouvernement du Québec
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