Journal of Pediatric Neurology
DOI: 10.1055/s-0041-1727099
Review Article

The Spectrum of KCNQ2- and KCNQ3-Related Epilepsy

Anna Portale*
1  Unit of Pediatrics, Avola Hospital, Siracusa, Italy
,
Mattia Comella*
2  Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Giulia Salomone
2  Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Alessandra Di Nora
2  Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Lidia Marino
2  Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Roberta Leonardi
3  Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Andrea D. Praticò
3  Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Raffaele Falsaperla
4  Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
5  Unit of Neonatal Intensive Care and Neonatology, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
› Author Affiliations

Abstract

KCNQ genes encode for a family of six transmembrane domains, single pore-loop, and K+ channel α-subunits that have a wide range of physiological correlates. In the brain, KCNQ2 and KCNQ3 heteromultimers are thought to underlie the M-current which is essential in raising the threshold for firing an action potential; mutations in these genes may cause several types of infantile epilepsies. KCNQ2-related disorders represent a continuum of overlapping neonatal epileptic phenotypes that range from KCNQ2 benign familial neonatal epilepsy (BFNE), a seizure disorder that occur in children who typically have a normal psychomotor development and are inherited as an autosomal dominant trait, to KCNQ2 early-onset epileptic encephalopathy (EOEE) as the result of a de novo pathogenic variant. KCNQ3-related disorders are rarer and include BFNE, benign familial infantile epilepsy and KCNQ3-related epileptic encephalopathy with intellectual disability with or without seizures and/or cortical visual impairment. For both KCNQ2- and KCNQ3-related disorders, it is possible to use several drugs for different classes of mutations (i.e., gain of function vs. loss of function), and usually their effects vary in relation to the clinical presentation and the phenotype of the patient. However, KCNQ2-EOEE patients have a worse response to treatment than KCNQ2-BFNE patients and usually become drug resistant with multiple daily seizures.

* Both the authors have equally contributed to the present paper.




Publication History

Received: 13 September 2020

Accepted: 12 January 2021

Publication Date:
13 April 2021 (online)

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