Consensus recommendations for next-generation sequencing-based genetic testing in Rare Neurological diseases

Area of Science:

• Genetics
• Neurology
• Molecular Diagnostics

Background:

• External quality assessment (EQA) schemes are crucial for evaluating diagnostic performance.
• Next-generation sequencing (NGS) is increasingly used for diagnosing rare neurological disorders (RND).
• Previous EQA rounds highlighted significant variability and limitations in genetic testing reports for RND.

Purpose of the Study:

• To improve and harmonize the quality and completeness of genetic testing reports in NGS diagnostics for RND.
• To develop evidence-based recommendations for reporting in RND genetic diagnostics.
• To address identified limitations from EQA findings.

Main Methods:

• An adapted Delphi approach involving 31 experts was used to prioritize 28 identified topics.
• Expert groups formulated recommendations based on survey prioritization.
• A five-finger consensus method was employed for final approval of recommendations.

Main Results:

• All 28 prioritized topics were advanced for recommendation development.
• Consensus recommendations were achieved for 27 out of 28 topics.
• Recommendations cover gene panel composition, NGS limitations (e.g., repeat expansions), quality parameters, and variant interpretation sharing.

Conclusions:

• The developed recommendations are expected to enhance the quality of genetic testing and reporting in RND diagnostics.
• Harmonization across laboratories will facilitate easier comparison and interpretation of genetic testing reports.
• Consensus on patient selection criteria for NGS testing was not reached due to differing national healthcare policies.