Download PDF
Journal of Pediatric Neurology 2023; 21(03): 203-211
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
› Further Information
    Permissions and Reprints

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.

Keywords

KCNQ2 - KCNQ3 - neonatal epilepsy - benign neonatal epilepsy - neonatal epileptic encephalopathy

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




Publication History

Received: 13 September 2020

Accepted: 12 January 2021

Article published online:
13 April 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Miceli F, Soldovieri MV, Ambrosino P. et al. Early-onset epileptic encephalopathy caused by gain-of-function mutations in the voltage sensor of Kv7.2 and Kv7.3 potassium channel subunits. J Neurosci 2015; 35 (09) 3782-3793
    CrossrefPubMedGoogle Scholar
  • 2 Brown DA, Adams PR. Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone. Nature 1980; 283 (5748): 673-676
    CrossrefPubMedGoogle Scholar
  • 3 Coppola G, Castaldo P, Miraglia del Giudice E. et al. A novel KCNQ2 K+ channel mutation in benign neonatal convulsions and centrotemporal spikes. Neurology 2003; 61 (01) 131-134
    CrossrefPubMedGoogle Scholar
  • 4 Kothur K, Holman K, Farnsworth E. et al. Diagnostic yield of targeted massively parallel sequencing in children with epileptic encephalopathy. Seizure 2018; 59: 132-140
    CrossrefPubMedGoogle Scholar
  • 5 Ambrosino P, Freri E, Castellotti B. et al. Kv7.3 compound heterozygous variants in early onset encephalopathy reveal additive contribution of C-terminal residues to PIP2-dependent K+ channel gating. Mol Neurobiol 2018; 55 (08) 7009-7024
    CrossrefPubMedGoogle Scholar
  • 6 Maljevic S, Vejzovic S, Bernhard MK. et al. Novel KCNQ3 mutation in a large family with benign familial neonatal epilepsy: a rare cause of neonatal seizures. Mol Syndromol 2016; 7 (04) 189-196
    CrossrefPubMedGoogle Scholar
  • 7 Pavone P, Falsaperla R, Ruggieri M. et al. Clinical course of N-methyl-D-aspartate receptor encephalitis and the effectiveness of cyclophosphamide treatment. J Pediatr Neurol 2017; 15: 84-49
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Rett A, Teubel R. Neugeborenen Krampfe im Rahmen einer epileptisch belasten Familie. Wien Klin Wochenschr 1964; 76: 609-613
    PubMedGoogle Scholar
  • 9 Praticò AD, Falsaperla R, Ruggieri M, Corsello G, Pavone P. Prognostic challenges of SCN1A genetic mutations: report on two children with mild features. J Pediatr Neurol 2016; 14: 82-88
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Falsaperla R, Perciavalle V, Pavone P. et al. Unilateral eye blinking arising from the ictal ipsilateral occipital area. Clin EEG Neurosci 2016; 47 (03) 243-246
    CrossrefPubMedGoogle Scholar
  • 11 Incorpora G, Pavone P, Castellano-Chiodo D, Praticò AD, Ruggieri M, Pavone L. Gelastic seizures due to hypothalamic hamartoma: rapid resolution after endoscopic tumor disconnection. Neurocase 2013; 19 (05) 458-461
    CrossrefPubMedGoogle Scholar
  • 12 Pavone P, Falsaperla R, Ruggieri M, Praticò AD, Pavone L. West syndrome treatment: new roads for an old syndrome. Front Neurol 2013; 4: 113
    CrossrefPubMedGoogle Scholar
  • 13 Pavone P, Praticò AD, Falsaperla R. et al. Congenital generalized hypertrichosis: the skin as a clue to complex malformation syndromes. Ital J Pediatr 2015; 41: 55
    CrossrefPubMedGoogle Scholar
  • 14 Al Yazidi G, Shevell MI, Srour M. Two novel KCNQ2 mutations in 2 families with benign familial neonatal convulsions. Child Neurol Open 2017; 4: 2329048  × 17691396
    CrossrefPubMedGoogle Scholar
  • 15 Lee IC, Yang JJ, Li SYA. A KCNQ2 E515D mutation associated with benign familial neonatal seizures and continuous spike and waves during slow-wave sleep syndrome in Taiwan. J Formos Med Assoc 2017; 116 (09) 711-719
    CrossrefPubMedGoogle Scholar
  • 16 Vilan A, Mendes Ribeiro J, Striano P. et al. A distinctive ictal amplitude-integrated electroencephalography pattern in newborns with neonatal epilepsy associated with KCNQ2 mutations. Neonatology 2017; 112 (04) 387-393
    CrossrefPubMedGoogle Scholar
  • 17 Salafia S, Praticò AD, Pizzo E, Greco F, Di Bella D. Hemiconvulsion-hemiplegia-epilepsy syndrome. Magnetic resonance findings in a 3-year-old boy. Neurol Neurochir Pol 2013; 47 (06) 584-589
    CrossrefPubMedGoogle Scholar
  • 18 Barbagallo M, Ruggieri M, Incorpora G. et al. Infantile spasms in the setting of Sturge-Weber syndrome. Childs Nerv Syst 2009; 25 (01) 111-118
    CrossrefPubMedGoogle Scholar
  • 19 Ronen GM, Rosales TO, Connolly M, Anderson VE, Leppert M. Seizure characteristics in chromosome 20 benign familial neonatal convulsions. Neurology 1993; 43 (07) 1355-1360
    CrossrefPubMedGoogle Scholar
  • 20 Ishii A, Miyajima T, Kurahashi H. et al. KCNQ2 abnormality in BECTS: benign childhood epilepsy with centrotemporal spikes following benign neonatal seizures resulting from a mutation of KCNQ2. Epilepsy Res 2012; 102 (1-2): 122-125
    CrossrefPubMedGoogle Scholar
  • 21 Caltabiano R, Magro G, Polizzi A. et al. A mosaic pattern of INI1/SMARCB1 protein expression distinguishes Schwannomatosis and NF2-associated peripheral schwannomas from solitary peripheral schwannomas and NF2-associated vestibular schwannomas. Childs Nerv Syst 2017; 33 (06) 933-940
    CrossrefPubMedGoogle Scholar
  • 22 Pavone P, Briuglia S, Falsaperla R. et al. Wide spectrum of congenital anomalies including choanal atresia, malformed extremities, and brain and spinal malformations in a girl with a de novo 5.6-Mb deletion of 13q12.11-13q12.13. Am J Med Genet A 2014; 164A (07) 1734-1743
    CrossrefPubMedGoogle Scholar
  • 23 Pavone V, Signorelli SS, Praticò AD. et al. Total hemi-overgrowth in pigmentary mosaicism of the (hypomelanosis of) ITO type: eight case reports. Medicine (Baltimore) 2016; 95 (10) e2705
    CrossrefPubMedGoogle Scholar
  • 24 Pavone P, Praticò AD, Pavone V. et al. Ataxia in children: early recognition and clinical evaluation. Ital J Pediatr 2017; 43 (01) 6
    CrossrefPubMedGoogle Scholar
  • 25 Praticò AD, Pavone P, Scuderi MG. et al. Symptomatic hypocalcemia in an epileptic child treated with valproic acid plus lamotrigine: a case report. Cases J 2009; 2: 7394
    PubMedGoogle Scholar
  • 26 Pavone P, Rizzo R, Conti I. et al. Primary headaches in children: clinical findings on the association with other conditions. Int J Immunopathol Pharmacol 2012; 25 (04) 1083-1091
    CrossrefPubMedGoogle Scholar
  • 27 Gomis-Pérez C, Urrutia J, Marcé-Grau A. et al. Homomeric Kv7.2 current suppression is a common feature in KCNQ2 epileptic encephalopathy. Epilepsia 2019; 60 (01) 139-148
    CrossrefPubMedGoogle Scholar
  • 28 Pavone P, Praticò AD, Gentile G. et al. A neurocutaneous phenotype with paired hypo- and hyperpigmented macules, microcephaly and stunted growth as prominent features. Eur J Med Genet 2016; 59 (05) 283-289
    CrossrefPubMedGoogle Scholar
  • 29 Ruggieri M, Praticò AD, Caltabiano R, Polizzi A. Early history of the different forms of neurofibromatosis from ancient Egypt to the British Empire and beyond: First descriptions, medical curiosities, misconceptions, landmarks, and the persons behind the syndromes. Am J Med Genet A 2018; 176 (03) 515-550
    CrossrefPubMedGoogle Scholar
  • 30 Falsaperla R, Praticò AD, Ruggieri M. et al. Congenital muscular dystrophy: from muscle to brain. Ital J Pediatr 2016; 42 (01) 78
    CrossrefPubMedGoogle Scholar
  • 31 Ranieri C, Di Tommaso S, Loconte DC. et al. In vitro efficacy of ARQ 092, an allosteric AKT inhibitor, on primary fibroblast cells derived from patients with PIK3CA-related overgrowth spectrum (PROS). Neurogenetics 2018; 19 (02) 77-91
    CrossrefPubMedGoogle Scholar
  • 32 Ruggieri M, Praticò AD, Caltabiano R, Polizzi A. Rediagnosing one of Smith's patients (John McCann) with “neuromas tumours” (1849). Neurol Sci 2017; 38 (03) 493-499
    CrossrefPubMedGoogle Scholar
  • 33 Kasinathan A, Sankhyan N, Singhi P. KCNQ2 epileptic encephalopathy in early infancy. Indian J Pediatr 2017; 84 (11) 877-878
    CrossrefPubMedGoogle Scholar
  • 34 Reid ES, Williams H, Stabej PleQ. et al. Seizures due to a KCNQ2 mutation: treatment with vitamin B6. JIMD Rep 2016; 27: 79-84
    CrossrefPubMedGoogle Scholar
  • 35 Reif PS, Tsai MH, Helbig I, Rosenow F, Klein KM. Precision medicine in genetic epilepsies: break of dawn?. Expert Rev Neurother 2017; 17 (04) 381-392
    CrossrefPubMedGoogle Scholar
  • 36 Cornet MC, Sands TT, Cilio MR. Neonatal epilepsies: clinical management. Semin Fetal Neonatal Med 2018; 23 (03) 204-212
    CrossrefPubMedGoogle Scholar
  • 37 Mulkey SB, Ben-Zeev B, Nicolai J. et al. Neonatal nonepileptic myoclonus is a prominent clinical feature of KCNQ2 gain-of-function variants R201C and R201H. Epilepsia 2017; 58 (03) 436-445
    CrossrefPubMedGoogle Scholar
  • 38 Millichap JJ, Miceli F, De Maria M. et al. Infantile spasms and encephalopathy without preceding neonatal seizures caused by KCNQ2 R198Q, a gain-of-function variant. Epilepsia 2017; 58 (01) e10-e15
    CrossrefPubMedGoogle Scholar
  • 39 Kojima K, Shirai K, Kobayashi M. et al. A patient with early myoclonic encephalopathy (EME) with a de novo KCNQ2 mutation. Brain Dev 2018; 40 (01) 69-73
    CrossrefPubMedGoogle Scholar
  • 40 Devaux J, Abidi A, Roubertie A. et al. A Kv7.2 mutation associated with early onset epileptic encephalopathy with suppression-burst enhances Kv7/M channel activity. Epilepsia 2016; 57 (05) e87-e93
    CrossrefPubMedGoogle Scholar
  • 41 Schubert-Bast S, Hofstetter P, Fischer D, Schloesser R, Ramantani G, Kieslich M. Sodium channel blockers in KCNQ2-encephalopathy: lacosamide as a new treatment option. Seizure 2017; 51: 171-173
    CrossrefPubMedGoogle Scholar
  • 42 Duan H, Peng J, Kessi M, Yin F. De novo KCNQ2 mutation in one case of epilepsy of infancy with migrating focal seizures that evolved to infantile spasms. Child Neurol Open 2018; 5: 2329048  × 18767738
    CrossrefPubMedGoogle Scholar
  • 43 Olson HE, Kelly M, LaCoursiere CM. et al. Genetics and genotype-phenotype correlations in early onset epileptic encephalopathy with burst suppression. Ann Neurol 2017; 81 (03) 419-429
    CrossrefPubMedGoogle Scholar
  • 44 Ruggieri M, Praticò AD, Scuderi A, Sorge G, Polizzi A. The multiple faces of artwork diagnoses. Lancet Neurol 2017; 16 (06) 417-418
    CrossrefPubMedGoogle Scholar
  • 45 Ruggieri M, Praticò AD, Serra A. et al. Early history of neurofibromatosis type 2 and related forms: earliest descriptions of acoustic neuromas, medical curiosities, misconceptions, landmarks and the pioneers behind the eponyms. Childs Nerv Syst 2017; 33 (04) 549-560
    CrossrefPubMedGoogle Scholar
  • 46 Spagnoli C, Salerno GG, Iodice A, Frattini D, Pisani F, Fusco C. KCNQ2 encephalopathy: a case due to a de novo deletion. Brain Dev 2018; 40 (01) 65-68
    CrossrefPubMedGoogle Scholar
  • 47 Hewson S, Puka K, Mercimek-Mahmutoglu S. Variable expressivity of a likely pathogenic variant in KCNQ2 in a three-generation pedigree presenting with intellectual disability with childhood onset seizures. Am J Med Genet A 2017; 173 (08) 2226-2230
    CrossrefPubMedGoogle Scholar
  • 48 Knuutinen O, Kousi M, Suo-Palosaari M. et al. Neonatal alexander disease: novel GFAP mutation and comparison to previously published cases. Neuropediatrics 2018; 49 (04) 256-261
    Article in Thieme ConnectPubMedGoogle Scholar
  • 49 Zhou P, He N, Zhang JW. et al. Novel mutations and phenotypes of epilepsy-associated genes in epileptic encephalopathies. Genes Brain Behav 2018; 17 (08) e12456
    CrossrefPubMedGoogle Scholar
  • 50 Allen NM, Mannion M, Conroy J. et al. The variable phenotypes of KCNQ-related epilepsy. Epilepsia 2014; 55 (09) e99-e105
    CrossrefPubMedGoogle Scholar
  • 51 Miao P, Feng J, Guo Y. et al. Genotype and phenotype analysis using an epilepsy-associated gene panel in Chinese pediatric epilepsy patients. Clin Genet 2018; 94 (06) 512-520
    CrossrefPubMedGoogle Scholar
  • 52 Orhan G, Bock M, Schepers D. et al. Dominant-negative effects of KCNQ2 mutations are associated with epileptic encephalopathy. Ann Neurol 2014; 75 (03) 382-394
    CrossrefPubMedGoogle Scholar
  • 53 Miceli F, Soldovieri MV, Joshi N, Weckhuysen S, Cooper EC, Taglialatela M. KCNQ3-related disorders. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A. eds. GeneReviews. Seattle WA: University of Washington, Seattle; 1993-2021
    Google Scholar
  • 54 Milh M, Boutry-Kryza N, Sutera-Sardo J. et al. Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2 . Orphanet J Rare Dis 2013; 8: 80
    CrossrefPubMedGoogle Scholar
  • 55 Borgatti R, Zucca C, Cavallini A. et al. A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation. Neurology 2004; 63 (01) 57-65
    CrossrefPubMedGoogle Scholar
  • 56 Grinton BE, Heron SE, Pelekanos JT. et al. Familial neonatal seizures in 36 families: Clinical and genetic features correlate with outcome. Epilepsia 2015; 56 (07) 1071-1080
    CrossrefPubMedGoogle Scholar
  • 57 Soldovieri MV, Boutry-Kryza N, Milh M. et al. Novel KCNQ2 and KCNQ3 mutations in a large cohort of families with benign neonatal epilepsy: first evidence for an altered channel regulation by syntaxin-1A. Hum Mutat 2014; 35 (03) 356-367
    CrossrefPubMedGoogle Scholar
  • 58 Zeng Q, Yang X, Zhang J. et al. Genetic analysis of benign familial epilepsies in the first year of life in a Chinese cohort. J Hum Genet 2018; 63 (01) 9-18
    CrossrefPubMedGoogle Scholar
  • 59 Zhang Q, Li J, Zhao Y, Bao X, Wei L, Wang J. Gene mutation analysis of 175 Chinese patients with early-onset epileptic encephalopathy. Clin Genet 2017; 91 (05) 717-724
    CrossrefPubMedGoogle Scholar
  • 60 Ortega-Moreno L, Giráldez BG, Soto-Insuga V. et al; Grupo Español de Genética de las Epilepsias de la Infancia (GEGEI). Molecular diagnosis of patients with epilepsy and developmental delay using a customized panel of epilepsy genes. PLoS One 2017; 12 (11) e0188978
    CrossrefPubMedGoogle Scholar
  • 61 Arafat A, Jing P, Ma Y. et al. Unexplained early infantile epileptic encephalopathy in han chinese children: next-generation sequencing and phenotype enriching. Sci Rep 2017; 7: 46227
    CrossrefPubMedGoogle Scholar
  • 62 Liu J, Tong L, Song S. et al. Novel and de novo mutations in pediatric refractory epilepsy. Mol Brain 2018; 11 (01) 48
    CrossrefPubMedGoogle Scholar
  • 63 Ruggieri M, Milone P, Pavone P. et al. Nevus vascularis mixtus (cutaneous vascular twin nevi) associated with intracranial vascular malformation of the Dyke-Davidoff-Masson type in two patients. Am J Med Genet A 2012; 158A (11) 2870-2880
    CrossrefPubMedGoogle Scholar
  • 64 Ruggieri M, Iannetti P, Pavone L. Delineation of a newly recognized neurocutaneous malformation syndrome with “cutis tricolor”. Am J Med Genet A 2003; 120A (01) 110-116
    CrossrefPubMedGoogle Scholar
  • 65 Pavone P, Praticò AD, Vitaliti G. et al. Hydranencephaly: cerebral spinal fluid instead of cerebral mantles. Ital J Pediatr 2014; 40: 79
    CrossrefPubMedGoogle Scholar
  • 66 Ruggieri M, Praticò AD, Serra A. et al. Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies. Acta Otorhinolaryngol Ital 2016; 36 (05) 345-367
    PubMedGoogle Scholar
  • 67 Polizzi A, Pavone P, Ciancio E, La Rosa C, Sorge G, Ruggieri M. Hypertrichosis cubiti (hairy elbow syndrome): a clue to a malformation syndrome. J Pediatr Endocrinol Metab 2005; 18 (10) 1019-1025
    CrossrefPubMedGoogle Scholar
  • 68 Polizzi A, Pavone P, Parano E, Incorpora G, Ruggieri M. Lack of progression of brain atrophy in Aicardi-Goutières syndrome. Pediatr Neurol 2001; 24 (04) 300-302
    CrossrefPubMedGoogle Scholar
  • 69 Polizzi A, Coghill S, McShane MA, Squier W. Acute ataxia complicating Langherans cell histiocytosis. Arch Dis Child 2002; 86 (02) 130-131
    CrossrefPubMedGoogle Scholar
  • 70 Lauritano A, Moutton S, Longobardi E. et al. A novel homozygous KCNQ3 loss-of-function variant causes non-syndromic intellectual disability and neonatal-onset pharmacodependent epilepsy. Epilepsia Open 2019; 4 (03) 464-475
    CrossrefPubMedGoogle Scholar
  • 71 Sands TT, Miceli F, Lesca G. et al. Autism and developmental disability caused by KCNQ3 gain-of-function variants. Ann Neurol 2019; 86 (02) 181-192
    CrossrefPubMedGoogle Scholar
  • 72 Kuersten M, Tacke M, Gerstl L, Hoelz H, Stülpnagel CV, Borggraefe I. Antiepileptic therapy approaches in KCNQ2 related epilepsy: a systematic review. Eur J Med Genet 2020; 63 (01) 103628
    CrossrefPubMedGoogle Scholar
  • 73 Tulloch JK, Carr RR, Ensom MH. A systematic review of the pharmacokinetics of antiepileptic drugs in neonates with refractory seizures. J Pediatr Pharmacol Ther 2012; 17 (01) 31-44
    PubMedGoogle Scholar
  • 74 Sands TT, Balestri M, Bellini G. et al. Rapid and safe response to low-dose carbamazepine in neonatal epilepsy. Epilepsia 2016; 57 (12) 2019-2030
    CrossrefPubMedGoogle Scholar
  • 75 Kato M, Yamagata T, Kubota M. et al. Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation. Epilepsia 2013; 54 (07) 1282-1287
    CrossrefPubMedGoogle Scholar
  • 76 Brodie MJ. Sodium channel blockers in the treatment of epilepsy. CNS Drugs 2017; 31 (07) 527-534
    CrossrefPubMedGoogle Scholar
  • 77 Ko A, Youn SE, Kim SH. et al. Targeted gene panel and genotype-phenotype correlation in children with developmental and epileptic encephalopathy. Epilepsy Res 2018; 141: 48-55
    CrossrefPubMedGoogle Scholar
  • 78 Falsaperla R, D'Angelo G, Praticò AD. et al. Ketogenic diet for infants with epilepsy: a literature review. Epilepsy Behav 2020; 112: 107361
    CrossrefPubMedGoogle Scholar
  • 79 Serino D, Specchio N, Pontrelli G, Vigevano F, Fusco L. Video/EEG findings in a KCNQ2 epileptic encephalopathy: a case report and revision of literature data. Epileptic Disord 2013; 15 (02) 158-165
    CrossrefPubMedGoogle Scholar
  • 80 Pratico AD, Longo L, Mansueto S. et al. Off-label use of drugs and adverse drug reactions in pediatric units: a prospective, multicenter study. Curr Drug Saf 2018; 13 (03) 200-207
    CrossrefPubMedGoogle Scholar
  • 81 Pavone P, Praticò AD, Ruggieri M. et al. Acquired peripheral neuropathy: a report on 20 children. Int J Immunopathol Pharmacol 2012; 25 (02) 513-517
    CrossrefPubMedGoogle Scholar
  • 82 Pratico AD, Ruggieri M, Falsaperla R, Pavone P. A probable topiramate-induced limbs paraesthesia and rigid fingers flexion. Curr Drug Saf 2018; 13 (02) 131-136
    CrossrefPubMedGoogle Scholar
  • 83 Ruggieri M, Polizzi A, Marceca GP, Catanzaro S, Praticò AD, Di Rocco C. Introduction to phacomatoses (neurocutaneous disorders) in childhood. Childs Nerv Syst 2020; 36 (10) 2229-2268
    CrossrefPubMedGoogle Scholar
  • 84 Porter RJ, Burdette DE, Gil-Nagel A. et al. Retigabine as adjunctive therapy in adults with partial-onset seizures: integrated analysis of three pivotal controlled trials. Epilepsy Res 2012; 101 (1-2): 103-112
    CrossrefPubMedGoogle Scholar
  • 85 Weckhuysen S, Ivanovic V, Hendrickx R. et al; KCNQ2 Study Group. Extending the KCNQ2 encephalopathy spectrum: clinical and neuroimaging findings in 17 patients. Neurology 2013; 81 (19) 1697-1703
    CrossrefPubMedGoogle Scholar
  • 86 Singh NA, Westenskow P, Charlier C. et al; BFNC Physician Consortium. KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum. Brain 2003; 126 (Pt 12): 2726-2737
    CrossrefPubMedGoogle Scholar