BACKGROUND: Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications. OBJECTIVES: We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity). METHODS: We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses. RESULTS: Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81. CONCLUSIONS: The algorithm is a useful predictive tool and could be integrated into dystonia routine diagnostic protocols. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

1st Department of Neurology Faculty of Medicine St Anne's University Hospital and CEITEC Masaryk University Brno Czech Republic

2nd Department of Neurology Faculty of Medicine Comenius University University Hospital Bratislava Bratislava Slovakia

Academic Center for Education Culture and Research Khorasan Razavi Mashhad Iran

Department of General Pediatrics Neonatology and Pediatric Cardiology University Children's Hospital Medical Faculty Heinrich Heine University Düsseldorf Germany

Department of Medical Genetics Faculty of Medicine Mashhad University of Medical Sciences Mashhad Iran

Department of Neurology Charles University 1st Faculty of Medicine and General University Hospital Prague Prague Czech Republic

Department of Neurology Faculty of Medicine Mashhad University of Medical Sciences Qaem Medical Center Mashhad Iran

Department of Neurology Ludwig Maximilians University Munich Germany

Department of Neurology Medical University Innsbruck Innsbruck Austria

Department of Neurology Medical University of Vienna Vienna Austria

Department of Neurology P J Safarik University Kosice Slovak Republic

Department of Neurology University Hospital Hradec Kralove Czech Republic

Department of Neurology University Hospital of L Pasteur Kosice Slovak Republic

Department of Neurology Zvolen Hospital Zvolen Slovakia

Department of Neuropediatrics and Muscle Disorders University Medical Center Faculty of Medicine University of Freiburg Freiburg Germany

Department of Pediatrics Medical University Innsbruck Innsbruck Austria

Hospital for Neuropediatrics and Neurological Rehabilitation Centre of Epilepsy for Children and Adolescents Schoen Klinik Vogtareuth Vogtareuth Germany

Hospital Písek Písek Czech Republic

Inborn Errors of Metabolism Pediatric Intensive Care Unit University Hospital of Nantes Nantes France

Institute of Human Genetics Technical University of Munich Munich Germany

Institute of Neurogenomics Helmholtz Zentrum München Munich Germany

kbo Kinderzentrum München Munich Germany

Klinik für Neurologie Asklepios Fachklinikum Stadtroda Stadtroda Germany

Klinik und Poliklinik für Neurologie Klinikum rechts der Isar Technische Universität München Munich Germany

Lehrstuhl für Neurogenetik Technische Universität München Munich Germany

Lehrstuhl für Sozialpädiatrie Technische Universität München Munich Germany

Ludwig Maximilian University of Munich Munich Germany

Munich Cluster for Systems Neurology Munich Germany

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