TY - JOUR
T1 - Genetic and phenotypic landscape of pediatric-onset epilepsy in 142 Indian families
T2 - Counseling and therapeutic implications
AU - Majethia, Purvi
AU - Kaur, Namanpreet
AU - Mascarenhas, Selinda
AU - Rao, Lakshmi Priya
AU - Pande, Shruti
AU - Narayanan, Dhanya Lakshmi
AU - Bhat, Vivekananda
AU - Nayak, Shalini S.
AU - Nair, Karthik Vijay
AU - Prasannakumar, Adarsh Pooradan
AU - Chaurasia, Ankur
AU - Hunakunti, Bhagesh
AU - Jadhav, Nalesh
AU - Farooqui, Sheeba
AU - Yeole, Mayuri
AU - Kothiwale, Vishaka
AU - Naik, Rohit
AU - Bhat, Veena
AU - Aroor, Shrikiran
AU - Lewis, Leslie
AU - Purkayastha, Jayashree
AU - Bhat, Y. Ramesh
AU - Praveen, B. K.
AU - Yatheesha, B. L.
AU - Patil, Siddaramappa J.
AU - Nampoothiri, Sheela
AU - Kamath, Nutan
AU - Siddiqui, Shahyan
AU - Bielas, Stephanie
AU - Girisha, Katta Mohan
AU - Sharma, Suvasini
AU - Shukla, Anju
N1 - Publisher Copyright:
© 2024 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.
© 2024 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.
PY - 2024/2/19
Y1 - 2024/2/19
N2 - 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.
AB - 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.
KW - India
KW - epilepsy
KW - genetic testing
KW - genetics
KW - therapeutic implications
UR - http://www.scopus.com/inward/record.url?scp=85185651887&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85185651887&partnerID=8YFLogxK
U2 - 10.1111/cge.14495
DO - 10.1111/cge.14495
M3 - Article
C2 - 38374498
AN - SCOPUS:85185651887
SN - 0009-9163
JO - Clinical Genetics
JF - Clinical Genetics
ER -