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. 2021 Aug;36(8):1959-1964.
doi: 10.1002/mds.28614. Epub 2021 May 5.

Scoring Algorithm-Based Genomic Testing in Dystonia: A Prospective Validation Study

Michael Zech  1   2 , Robert Jech  3 , Sylvia Boesch  4 , Matej Škorvánek  5   6 , Ján Necpál  7 , Jana Švantnerová  8 , Matias Wagner  1   2 , Ariane Sadr-Nabavi  9   10   11 , Felix Distelmaier  12 , Martin Krenn  2   13 , Tereza Serranová  3 , Irena Rektorová  14 , Petra Havránková  3 , Alexandra Mosejová  5   6 , Iva Příhodová  3 , Jana Šarláková  15 , Kristína Kulcsarová  5   6 , Olga Ulmanová  3 , Karel Bechyně  16 , Miriam Ostrozovičová  5   6 , Vladimír Haň  5   6 , Joaquim Ribeiro Ventosa  5   6 , Theresa Brunet  2 , Riccardo Berutti  2 , Mohammad Shariati  10   11 , Ali Shoeibi  10 , Susanne A Schneider  17 , Alice Kuster  18 , Matthias Baumann  19 , David Weise  20 , Friederike Wilbert  21 , Wibke G Janzarik  21 , Matthias Eckenweiler  21 , Volker Mall  22   23 , Bernhard Haslinger  24 , Steffen Berweck  25   26 , Juliane Winkelmann #  1   2   27   28 , Konrad Oexle #  1   2
Affiliations

Scoring Algorithm-Based Genomic Testing in Dystonia: A Prospective Validation Study

Michael Zech et al. Mov Disord. 2021 Aug.

Abstract

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.

Keywords: diagnostic yield; dystonia; exome sequencing; prediction; rare disease; scoring algorithm.

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