TY - JOUR

T1 - Epilepsy syndromes in the first year of life and usefulness of genetic testing for precision therapy

AU - Bayat, Allan

AU - Bayat, Michael

AU - Rubboli, Guido

AU - Møller, Rikke S.

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021

Y1 - 2021

N2 - The high pace of gene discovery has resulted in thrilling advances in the field of epilepsy genetics. Clinical testing with comprehensive gene panels, exomes, or genomes are now increas-ingly available and have led to a significant higher diagnostic yield in early-onset epilepsies and enabled precision medicine approaches. These have been instrumental in providing insights into the pathophysiology of both early-onset benign and self-limited syndromes and devastating developmental and epileptic encephalopathies (DEEs). Genetic heterogeneity is seen in many epilepsy syndromes such as West syndrome and epilepsy of infancy with migrating focal seizures (EIMFS), indicating that two or more genetic loci produce the same or similar phenotypes. At the same time, some genes such as SCN2A can be associated with a wide range of epilepsy syndromes ranging from self-limited familial neonatal epilepsy at the mild end to Ohtahara syndrome, EIFMS, West syndrome, Lennox–Gastaut syndrome, or unclassifiable DEEs at the severe end of the spectrum. The aim of this study was to review the clinical and genetic heterogeneity associated with epilepsy syndromes starting in the first year of life including: Self-limited familial neonatal, neonatal-infantile or infantile epilepsies, genetic epilepsy with febrile seizures plus spectrum, myoclonic epilepsy in infancy, Ohtahara syndrome, early myoclonic encephalopathy, West syndrome, Dravet syndrome, EIMFS, and unclassifiable DEEs. We also elaborate on the advantages and pitfalls of genetic testing in such conditions. Finally, we describe how a genetic diagnosis can potentially enable precision therapy in monogenic epilepsies and emphasize that early genetic testing is a cornerstone for such therapeutic strategies.

AB - The high pace of gene discovery has resulted in thrilling advances in the field of epilepsy genetics. Clinical testing with comprehensive gene panels, exomes, or genomes are now increas-ingly available and have led to a significant higher diagnostic yield in early-onset epilepsies and enabled precision medicine approaches. These have been instrumental in providing insights into the pathophysiology of both early-onset benign and self-limited syndromes and devastating developmental and epileptic encephalopathies (DEEs). Genetic heterogeneity is seen in many epilepsy syndromes such as West syndrome and epilepsy of infancy with migrating focal seizures (EIMFS), indicating that two or more genetic loci produce the same or similar phenotypes. At the same time, some genes such as SCN2A can be associated with a wide range of epilepsy syndromes ranging from self-limited familial neonatal epilepsy at the mild end to Ohtahara syndrome, EIFMS, West syndrome, Lennox–Gastaut syndrome, or unclassifiable DEEs at the severe end of the spectrum. The aim of this study was to review the clinical and genetic heterogeneity associated with epilepsy syndromes starting in the first year of life including: Self-limited familial neonatal, neonatal-infantile or infantile epilepsies, genetic epilepsy with febrile seizures plus spectrum, myoclonic epilepsy in infancy, Ohtahara syndrome, early myoclonic encephalopathy, West syndrome, Dravet syndrome, EIMFS, and unclassifiable DEEs. We also elaborate on the advantages and pitfalls of genetic testing in such conditions. Finally, we describe how a genetic diagnosis can potentially enable precision therapy in monogenic epilepsies and emphasize that early genetic testing is a cornerstone for such therapeutic strategies.

KW - Benign and self-limiting (familial) epilepsy syndromes

KW - Diagnostic yield

KW - Early-onset epilepsy

KW - Epilepsy genetics

KW - Epileptic encephalopathy

KW - Precision therapy

U2 - 10.3390/genes12071051

DO - 10.3390/genes12071051

M3 - Review

C2 - 34356067

AN - SCOPUS:85110711127

VL - 12

JO - Genes

JF - Genes

SN - 2073-4425

IS - 7

M1 - 1051

ER -