Objective: The reported yield from next generation sequencing (NGS) in Movement Disorder clinics is 11.3 – 22% [1,2]. We aimed to determine current practice and yield from genetic testing in our tertiary Movement Disorder clinics.

Background: Genetic testing is becoming increasingly important in clinical practice as we move towards precision medicine. The availability of NGS technologies, in particular whole genome sequencing (WGS), has significantly increased our ability to identify likely pathogenic variants. Growing knowledge of treatable rare disorders and bespoke monitoring based on accurate genetic diagnoses is becoming increasingly relevant in movement disorder clinics.

Following the 2018 publication of a National Genomics Test Directory for rare and inherited diseases in England, there has been a gradual transition to WGS as the standard of care. This has been routine practice in our centre since mid 2021. Through auditing our outcomes during this transition period we hope to optimise the use of WGS and allow future comparative studies.

Method: A retrospective review of all patients attending our tertiary Movement Disorder clinics and undergoing genetic testing between 1^st January 2019 and 1^st June 2021. Data collected included age at testing, family history and clinical phenotype.

Results: Genetic testing was performed on 3.9% of patients attending Movement Disorder clinics. 106 patients had a total of 144 tests (27% single gene, 73% gene panel/ NGS). The majority of NGS was done by gene panels/ targeted sequencing, with in house WGS becoming available during the final months of the audit period. 29% of patients had positive family history. Ataxia (25.4%, either isolated or dominant feature) was the most common clinical phenotype, followed by dystonia (18.9%), tremor (16%) and parkinsonism (15.1%). The overall yield of testing was 12.5% (18/144 tests) with 17% of patients receiving a positive genetic diagnosis (18/106). The yield from panel/ NGS was 10.5% (11/105), but was higher for the commonest phenotypic categories of ataxia – 33.3% (3/9), dystonia – 13.8% (4/29) and parkinsonism – 20% (2/10).

Conclusion: Real world data from our centre shows a yield from genetic testing comparable with other reports in the literature [1-6]. It is worth noting the period covered in this audit includes the challenging clinical environment during the Covid pandemic. A repeat evaluation is planned following full adoption of WGS.

References: 1.Reale C, Panteghini C, Carecchio M, Garavaglia B. The relevance of gene panels in movement disorders diagnosis: A lab perspective. Eur J Paediatr Neurol. 2018 Mar;22(2):285-291.

2.Montaut S, Tranchant C, Drouot N, Rudolf G, Guissart C, Tarabeux J, Stemmelen T, Velt A, Fourrage C, Nitschké P, Gerard B, Mandel JL, Koenig M, Chelly J, Anheim M; French Parkinson’s and Movement Disorders Consortium. Assessment of a Targeted Gene Panel for Identification of Genes Associated With Movement Disorders. JAMA Neurol. 2018 Oct 1;75(10):1234-1245.

3.Hadjivassiliou M, Martindale J, Shanmugarajah P, Grünewald RA, Sarrigiannis PG, Beauchamp N, Garrard K, Warburton R, Sanders DS, Friend D, Duty S, Taylor J, Hoggard N. Causes of progressive cerebellar ataxia: prospective evaluation of 1500 patients. J Neurol Neurosurg Psychiatry. 2017 Apr;88(4):301-309.

4.Ma J, Wang L, Yang YM, Wan XH. Targeted gene capture sequencing in diagnosis of dystonia patients. J Neurol Sci. 2018 Jul 15;390:36-41.

5.van Egmond ME, Lugtenberg CHA, Brouwer OF, Contarino MF, Fung VSC, Heiner-Fokkema MR, van Hilten JJ, van der Hout AH, Peall KJ, Sinke RJ, Roze E, Verschuuren-Bemelmans CC, Willemsen MA, Wolf NI, Tijssen MA, de Koning TJ. A post hoc study on gene panel analysis for the diagnosis of dystonia. Mov Disord. 2017 Apr;32(4):569-575.

6.Gorcenco S, Ilinca A, Almasoudi W, Kafantari E, Lindgren AG, Puschmann A. New generation genetic testing entering the clinic. Parkinsonism Relat Disord. 2020 Apr;73:72-84.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/outcomes-from-genetic-testing-in-a-uk-movement-disorder-clinic/