TY - JOUR
T1 - DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHIES
T2 - FROM GENETIC HETEROGENEITY TO PHENOTYPIC CONTINUUM
AU - Guerrini, Renzo
AU - Conti, Valerio
AU - Mantegazza, Massimo
AU - Balestrini, Simona
AU - Galanopoulou, Aristea S.
AU - Benfenati, Fabio
N1 - Publisher Copyright:
© 2023 the American Physiological Society.
PY - 2023/1
Y1 - 2023/1
N2 - Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of disorders characterized by early-onset, often severe epileptic seizures and EEG abnormalities on a background of developmental impairment that tends to worsen as a consequence of epilepsy. DEEs may result from both nongenetic and genetic etiologies. Genetic DEEs have been associated with mutations in many genes involved in different functions including cell migration, proliferation, and organization, neuronal excitability, and synapse transmission and plas-ticity. Functional studies performed in different animal models and clinical trials on patients have contributed to elucidate pathophysiological mechanisms underlying many DEEs and have explored the efficacy of different treatments. Here, we provide an extensive review of the phenotypic spectrum included in the DEEs and of the genetic determinants and pathophysiological mechanisms underlying these conditions. We also provide a brief overview of the most effective treatment now available and of the emerging therapeutic approaches.
AB - Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of disorders characterized by early-onset, often severe epileptic seizures and EEG abnormalities on a background of developmental impairment that tends to worsen as a consequence of epilepsy. DEEs may result from both nongenetic and genetic etiologies. Genetic DEEs have been associated with mutations in many genes involved in different functions including cell migration, proliferation, and organization, neuronal excitability, and synapse transmission and plas-ticity. Functional studies performed in different animal models and clinical trials on patients have contributed to elucidate pathophysiological mechanisms underlying many DEEs and have explored the efficacy of different treatments. Here, we provide an extensive review of the phenotypic spectrum included in the DEEs and of the genetic determinants and pathophysiological mechanisms underlying these conditions. We also provide a brief overview of the most effective treatment now available and of the emerging therapeutic approaches.
KW - channelopathies
KW - developmental and epileptic encephalopathies
KW - epileptogenesis
KW - personalized treatment approaches
KW - synaptopathies
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U2 - 10.1152/physrev.00063.2021
DO - 10.1152/physrev.00063.2021
M3 - Review article
C2 - 35951482
AN - SCOPUS:85140144534
SN - 0031-9333
VL - 103
SP - 433
EP - 513
JO - Physiological Reviews
JF - Physiological Reviews
IS - 1
ER -