Genetic and phenotypic landscape of pediatric-onset epilepsy in 142 Indian families: Counseling and therapeutic implications.

Autor: Majethia P; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Kaur N; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Mascarenhas S; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Rao LP; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Pande S; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Narayanan DL; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Bhat V; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Nayak SS; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Nair KV; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Prasannakumar AP; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Chaurasia A; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India.; Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK., Hunakunti B; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Jadhav N; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Farooqui S; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Yeole M; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Kothiwale V; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Naik R; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Bhat V; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Aroor S; Department of Paediatrics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Lewis L; Department of Paediatrics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Purkayastha J; Department of Paediatrics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Bhat YR; Department of Paediatrics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Praveen BK; Department of Pediatrics, Father Muller Medical College Hospital, Mangalore, India., Yatheesha BL; Paediatric neurology, Dheemahi Child Neurology and Development Center, Shimoga, India., Patil SJ; Division of Medical Genetics, Narayana Hrudayalaya Hospitals/Mazumdar-Shaw Medical Center, Bangalore, India., Nampoothiri S; Department of Pediatric Genetics, Amrita Institute of Medical Sciences & Research Centre, Cochin, India., Kamath N; Department of Paediatrics, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India., Siddiqui S; Department of Neuro and Vascular Interventional Radiology, Yashoda Hospitals, Hyderabad, India., Bielas S; Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA., Girisha KM; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India.; Suma Genomics Private Limited, Manipal Center for Biotherapeutics Research, Manipal Academy of Higher Education, Manipal, India.; Department of Genetics, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman., Sharma S; Neurology Division, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India., Shukla A; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2024 Jun; Vol. 105 (6), pp. 639-654. Date of Electronic Publication: 2024 Feb 19.
DOI: 10.1111/cge.14495
Abstrakt: The application of genomic technologies has led to unraveling of the complex genetic landscape of disorders of epilepsy, gaining insights into their underlying disease mechanisms, aiding precision medicine, and providing informed genetic counseling. We herein present the phenotypic and genotypic insights from 142 Indian families with epilepsy with or without comorbidities. Based on the electroclinical findings, epilepsy syndrome diagnosis could be made in 44% (63/142) of the families adopting the latest proposal for the classification by the ILAE task force (2022). Of these, 95% (60/63) of the families exhibited syndromes with developmental epileptic encephalopathy or progressive neurological deterioration. A definitive molecular diagnosis was achieved in 74 of 142 (52%) families. Infantile-onset epilepsy was noted in 81% of these families (61/74). Fifty-five monogenic, four chromosomal, and one imprinting disorder were identified in 74 families. The genetic variants included 65 (96%) single-nucleotide variants/small insertion-deletions, 1 (2%) copy-number variant, and 1 (2%) triplet-repeat expansion in 53 epilepsy-associated genes causing monogenic disorders. Of these, 35 (52%) variants were novel. Therapeutic implications were noted in 51% of families (38/74) with definitive diagnosis. Forty-one out of 66 families with monogenic disorders exhibited autosomal recessive and inherited autosomal dominant disorders with high risk of recurrence.
(© 2024 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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