Margie A Ream1, Mohamad A Mikati2. 1. Duke University Medical Center, Department of Pediatrics, Division of Pediatric Neurology, USA. 2. Duke University Medical Center, Department of Pediatrics, Division of Pediatric Neurology, USA. Electronic address: mohamad.mikati@duke.edu.
Abstract
RATIONALE: The utility of genetic testing in pediatric drug-resistant epilepsy (PDRE), its yield in "real life" clinical practice, and the practical implications of such testing are yet to be determined. GOAL: To start to address the above gaps in our knowledge as they apply to a patient population seen in a tertiary care center. METHODS: We retrospectively reviewed our experience with the use of clinically available genetic tests in the diagnosis and management of PDRE in one clinic over one year. Genetic testing included, depending on clinical judgment, one or more of the following: karyotype, chromosomal microarray, single gene sequencing, gene sequencing panels, and/or whole exome sequencing (WES). RESULTS: We were more likely to perform genetic testing in patients with developmental delay, epileptic encephalopathy, and generalized epilepsy. In our unique population, the yield of specific genetic diagnosis was relatively high: karyotype 14.3%, microarray 16.7%, targeted single gene sequencing 15.4%, gene panels 46.2%, and WES 16.7%. Overall yield of diagnosis from at least one of the above tests was 34.5%. Disease-causing mutations that were not clinically suspected based on the patients' phenotypes and representing novel phenotypes were found in 6.9% (2/29), with an additional 17.2% (5/29) demonstrating pharmacologic variants. Three patients were incidentally found to be carriers of recessive neurologic diseases (10.3%). Variants of unknown significance (VUSs) were identified in 34.5% (10/29). CONCLUSIONS: We conclude that genetic testing had at least some utility in our patient population of PDRE, that future similar larger studies in various populations are warranted, and that clinics offering such tests must be prepared to address the complicated questions raised by the results of such testing.
RATIONALE: The utility of genetic testing in pediatric drug-resistant epilepsy (PDRE), its yield in "real life" clinical practice, and the practical implications of such testing are yet to be determined. GOAL: To start to address the above gaps in our knowledge as they apply to a patient population seen in a tertiary care center. METHODS: We retrospectively reviewed our experience with the use of clinically available genetic tests in the diagnosis and management of PDRE in one clinic over one year. Genetic testing included, depending on clinical judgment, one or more of the following: karyotype, chromosomal microarray, single gene sequencing, gene sequencing panels, and/or whole exome sequencing (WES). RESULTS: We were more likely to perform genetic testing in patients with developmental delay, epileptic encephalopathy, and generalized epilepsy. In our unique population, the yield of specific genetic diagnosis was relatively high: karyotype 14.3%, microarray 16.7%, targeted single gene sequencing 15.4%, gene panels 46.2%, and WES 16.7%. Overall yield of diagnosis from at least one of the above tests was 34.5%. Disease-causing mutations that were not clinically suspected based on the patients' phenotypes and representing novel phenotypes were found in 6.9% (2/29), with an additional 17.2% (5/29) demonstrating pharmacologic variants. Three patients were incidentally found to be carriers of recessive neurologic diseases (10.3%). Variants of unknown significance (VUSs) were identified in 34.5% (10/29). CONCLUSIONS: We conclude that genetic testing had at least some utility in our patient population of PDRE, that future similar larger studies in various populations are warranted, and that clinics offering such tests must be prepared to address the complicated questions raised by the results of such testing.
Authors: Liedewei Van de Vondel; Jonathan De Winter; Danique Beijer; Giulia Coarelli; Melanie Wayand; Robin Palvadeau; Martje G Pauly; Katrin Klein; Maren Rautenberg; Léna Guillot-Noël; Tine Deconinck; Atay Vural; Sibel Ertan; Okan Dogu; Hilmi Uysal; Vesna Brankovic; Rebecca Herzog; Alexis Brice; Alexandra Durr; Stephan Klebe; Friedrich Stock; Almut Turid Bischoff; Tim W Rattay; María-Jesús Sobrido; Giovanna De Michele; Peter De Jonghe; Thomas Klopstock; Katja Lohmann; Ginevra Zanni; Filippo M Santorelli; Vincent Timmerman; Tobias B Haack; Stephan Züchner; Rebecca Schüle; Giovanni Stevanin; Matthis Synofzik; A Nazli Basak; Jonathan Baets Journal: Mov Disord Date: 2022-02-12 Impact factor: 9.698
Authors: Steffen Syrbe; Frederike L Harms; Elena Parrini; Martino Montomoli; Ulrike Mütze; Katherine L Helbig; Tilman Polster; Beate Albrecht; Ulrich Bernbeck; Ellen van Binsbergen; Saskia Biskup; Lydie Burglen; Jonas Denecke; Bénédicte Heron; Henrike O Heyne; Georg F Hoffmann; Frauke Hornemann; Takeshi Matsushige; Ryuki Matsuura; Mitsuhiro Kato; G Christoph Korenke; Alma Kuechler; Constanze Lämmer; Andreas Merkenschlager; Cyril Mignot; Susanne Ruf; Mitsuko Nakashima; Hirotomo Saitsu; Hannah Stamberger; Tiziana Pisano; Jun Tohyama; Sarah Weckhuysen; Wendy Werckx; Julia Wickert; Francesco Mari; Nienke E Verbeek; Rikke S Møller; Bobby Koeleman; Naomichi Matsumoto; William B Dobyns; Domenica Battaglia; Johannes R Lemke; Kerstin Kutsche; Renzo Guerrini Journal: Brain Date: 2017-09-01 Impact factor: 13.501
Authors: Hadley Stevens Smith; J Michael Swint; Seema R Lalani; Jose-Miguel Yamal; Marcia C de Oliveira Otto; Stephan Castellanos; Amy Taylor; Brendan H Lee; Heidi V Russell Journal: Genet Med Date: 2018-05-14 Impact factor: 8.822