Seizures are the most common neurological manifestation in the newborn period, with an estimated incidence of 1.8–3.5 per 1000 live births. Prolonged or intractable seizures have a detrimental effect on cognition and brain function in experimental animals and are associated with adverse long-term neurodevelopmental sequelae and an increased risk of post-neonatal epilepsy in humans. The developing brain is particularly susceptible to the potentially severe effects of epilepsy, and epilepsy, especially when refractory to medications, often results in a developmental and epileptic encephalopathy (DEE) with developmental arrest or regression. DEEs can be primarily attributed to genetic causes. Given the critical role of potassium (K+) currents with distinct subcellular localization, biophysical properties, modulation, and pharmacological profile in regulating intrinsic electrical properties of neurons and their responsiveness to synaptic inputs, it is not too surprising that genetic research in the past two decades has identified several K+ channel genes as responsible for a large fraction of DEE. In the present article, we review the genetically determined epileptic channelopathies affecting three members of the Kv7 family, namely Kv7.2 (KCNQ2), Kv7.3 (KCNQ3), and Kv7.5 (KCNQ5); we review the phenotypic spectrum of Kv7-related epileptic channelopathies, the different genetic and pathogenetic mechanisms, and the emerging genotype-phenotype correlations which may prove crucial for prognostic predictions, disease management, parental counseling, and individually tailored therapeutic attempts.
Epileptic channelopathies caused by neuronal Kv7 (KCNQ) channel dysfunction
Ambrosino P.;
2020-01-01
Abstract
Seizures are the most common neurological manifestation in the newborn period, with an estimated incidence of 1.8–3.5 per 1000 live births. Prolonged or intractable seizures have a detrimental effect on cognition and brain function in experimental animals and are associated with adverse long-term neurodevelopmental sequelae and an increased risk of post-neonatal epilepsy in humans. The developing brain is particularly susceptible to the potentially severe effects of epilepsy, and epilepsy, especially when refractory to medications, often results in a developmental and epileptic encephalopathy (DEE) with developmental arrest or regression. DEEs can be primarily attributed to genetic causes. Given the critical role of potassium (K+) currents with distinct subcellular localization, biophysical properties, modulation, and pharmacological profile in regulating intrinsic electrical properties of neurons and their responsiveness to synaptic inputs, it is not too surprising that genetic research in the past two decades has identified several K+ channel genes as responsible for a large fraction of DEE. In the present article, we review the genetically determined epileptic channelopathies affecting three members of the Kv7 family, namely Kv7.2 (KCNQ2), Kv7.3 (KCNQ3), and Kv7.5 (KCNQ5); we review the phenotypic spectrum of Kv7-related epileptic channelopathies, the different genetic and pathogenetic mechanisms, and the emerging genotype-phenotype correlations which may prove crucial for prognostic predictions, disease management, parental counseling, and individually tailored therapeutic attempts.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
