Exome sequencing for patients with developmental and epileptic encephalopathies in clinical practice.

Autor: Scheffer IE; Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria.; Department of Paediatrics, The University of Melbourne, Victoria.; Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria.; Murdoch Children's Research Institute, Parkville, Victoria., Bennett CA; Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria., Gill D; TY Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, New South Wales., de Silva MG; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria.; Australian Genomics Health Alliance, Melbourne., Boggs K; Australian Genomics Health Alliance, Melbourne.; Sydney Children's Hospitals Network, Sydney., Marum J; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria., Baker N; Department of Paediatrics, The University of Melbourne, Victoria.; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria., Palmer EE; Clinical Genetics Service, Sydney Children's Hospital, Randwick, New South Wales., Howell KB; Department of Paediatrics, The University of Melbourne, Victoria.; Murdoch Children's Research Institute, Parkville, Victoria.; Department of Neurology, The Royal Children's Hospital, Parkville, Victoria, Australia.
Jazyk: angličtina
Zdroj: Developmental medicine and child neurology [Dev Med Child Neurol] 2023 Jan; Vol. 65 (1), pp. 50-57. Date of Electronic Publication: 2022 Jun 14.
DOI: 10.1111/dmcn.15308
Abstrakt: Aim: To assess the clinical utility of exome sequencing for patients with developmental and epileptic encephalopathies (DEEs).
Method: Over 2 years, patients with DEEs were recruited for singleton exome sequencing. Parental segregation was performed where indicated.
Results: Of the 103 patients recruited (54 males, 49 females; aged 2 weeks-17 years), the genetic aetiology was identified in 36 out of 103 (35%) with management implications in 13 out of 36. Exome sequencing revealed pathogenic or likely pathogenic variants in 30 out of 103 (29%) patients, variants of unknown significance in 39 out of 103 (38%), and 34 out of 103 (33%) were negative on exome analysis. After the description of new genetic diseases, a molecular diagnosis was subsequently made for six patients or through newly available high-density chromosomal microarray testing.
Interpretation: We demonstrate the utility of exome sequencing in routine clinical care of children with DEEs. We highlight that molecular diagnosis often leads to changes in management and informs accurate prognostic and reproductive counselling. Our findings reinforce the need for ongoing analysis of genomic data to identify the aetiology in patients in whom the cause is unknown. The implementation of genomic testing in the care of children with DEEs should become routine in clinical practice.
What This Paper Adds: The cause was identified in 35% of patients with developmental and epileptic encephalopathies. KCNQ2, CDKL5, SCN1A, and STXBP1 were the most frequently identified genes. Reanalysis of genomic data found the cause in an additional six patients. Genetic aetiology was identified in 41% of children with seizure onset under 2 years, compared to 18% with older onset. Finding the molecular cause led to management changes in 36% of patients with DEEs.
(© 2022 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)
Databáze: MEDLINE
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