KCNQ2
 encephalopathy: Delineation of the electroclinical phenotype and treatment response

Numis, Adam L.; Angriman, Marco; Sullivan, Joseph; Lewis, Ann; Striano, Pasquale; Nabbout, Rima; Cilio, Maria Roberta

doi:10.1212/wnl.0000000000000060

Cited by 139 publications

(130 citation statements)

References 6 publications

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“…The evidence that the mutation found in our patient causes epileptic encephalopathy is strong. Three patients have been reported previously to have the same de novo p.Arg210His mutation (Weckhuysen et al 2013;Numis et al 2014). All had NEE presenting with seizures on the first day of life and, similarly to our patient, two became seizure-free on administration of carbamazepine after failure of other AEDs.…”

Section: Discussionsupporting

confidence: 81%

See 1 more Smart Citation

Seizures Due to a KCNQ2 Mutation: Treatment with Vitamin B6

Reid¹,

Hj²,

Stabej³

et al. 2015

JIMD Reports

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There is increasing evidence that vitamin B 6 , given either as pyridoxine or pyridoxal 5 0 -phosphate, can sometimes result in improved seizure control in idiopathic epilepsy. Whole-exome sequencing was used to identify a de novo mutation (c.629G>A; p.Arg210His) in KCNQ2 in a 7-year-old patient whose neonatal seizures showed a response to pyridoxine and who had a high plasma to CSF pyridoxal 5 0 -phosphate ratio, usually indicative of an inborn error of vitamin B 6 metabolism. This mutation has been described in three other patients with neonatal epileptic encephalopathy. A review of the literature was performed to assess the effectiveness of vitamin B 6 treatment in patients with a KCNQ2 channelopathy. Twenty-three patients have been reported to have been trialled with B 6

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Section: Discussionsupporting

confidence: 81%

“…Thus modulation of one channel may affect the function of the channel complex. The other patient showed no improvement on carbamazepine treatment and died shortly afterwards due to respiratory failure in the context of infection (Numis et al 2014). None of these three patients were trialled on vitamin B 6 .…”

Section: Discussionmentioning

confidence: 99%

Seizures Due to a KCNQ2 Mutation: Treatment with Vitamin B6

Reid¹,

Hj²,

Stabej³

et al. 2015

JIMD Reports

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“…3,9 To date, only nine missense KCNQ3 mutations have been reported in families with early onset epilepsies; seven in BFNS, 5,7,8,[10][11][12][13][14] and two in patients with seizure occurrence in the infantile age. 15,16 In most families with KCNQ3 mutations, affected members showed a benign disease course including age of onset and remission of seizures, sensitivity to AEDs, no recurrence of seizures after the neonatal-infantile period, and normal neurocognitive development.…”

Section: Discussionmentioning

confidence: 99%

A novel KCNQ3 mutation in familial epilepsy with focal seizures and intellectual disability

et al. 2014

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SUMMARYMutations in the KCNQ2 gene encoding for voltage-gated potassium channel subunits have been found in patients affected with early onset epilepsies with wide phenotypic heterogeneity, ranging from benign familial neonatal seizures (BFNS) to epileptic encephalopathy with cognitive impairment, drug resistance, and characteristic electroencephalography (EEG) and neuroradiologic features. By contrast, only few KCNQ3 mutations have been rarely described, mostly in patients with typical BFNS. We report clinical, genetic, and functional data from a family in which early onset epilepsy and neurocognitive deficits segregated with a novel mutation in KCNQ3 (c.989G>T; p.R330L). Electrophysiological studies in mammalian cells revealed that incorporation of KCNQ3 R330L mutant subunits impaired channel function, suggesting a pathogenetic role for such mutation. The degree of functional impairment of channels incorporating KCNQ3 R330L subunits was larger than that of channels carrying another KCNQ3 mutation affecting the same codon but leading to a different amino acid substitution (p.R330C), previously identified in two families with typical BFNS. These data suggest that mutations in KCNQ3, similarly to KCNQ2, can be found in patients with more severe phenotypes including intellectual disability, and that the degree of the functional impairment caused by mutations at position 330 in KCNQ3 may contribute to clinical disease severity.

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“…KCNQ2-related epilepsies are characterized by recurrent seizures with onset during the first week after birth. Seizure semiology is characterized by asymmetric tonic posturing accompanied by apnea and desaturation, often followed by unilateral or bilateral clonic jerking [10,11]. Seizures may occur with a frequency of ≥10 per day [10,11].…”

Section: Introductionmentioning

confidence: 99%

A Distinctive Ictal Amplitude-Integrated Electroencephalography Pattern in Newborns with Neonatal Epilepsy Associated with KCNQ2 Mutations

Vilan¹,

Ribeiro

Striano

et al. 2017

Neonatology

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Background: Recurrent and prolonged seizures are harmful for the developing brain, emphasizing the importance of early seizure recognition and effective therapy. Amplitude-integrated electroencephalography (aEEG) has become a valuable tool to diagnose epileptic seizures, and, in parallel, genetic etiologies are increasingly being recognized, changing the paradigmof the workup and management of neonatal seizures. Objective: To report the ictal aEEG pattern in neonates with KCNQ2-related epilepsy. Subjects and Methods: In this multicenter descriptive study, clinical data and aEEG findings of 9 newborns with KCNQ2 mutations are reported. Results: Refractory seizures occurred in the early neonatal period with similar seizure type, including tonic features, apnea, and desaturation. A distinct aEEG seizure pattern, consisting of a sudden rise of the lower and upper margin of the aEEG, followed by a marked depression of the aEEG amplitude, was found in 8 of the 9 patients. Prompt recognition of this pattern led to early treatment with carbamazepine in the 2 most recent cases. Conclusion: Early recognition of the electroclinical phenotype by using aEEG may direct genetic testing and a precision medicine approach with sodium channel blockers in neonates with KCNQ2 mutations.

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KCNQ2 encephalopathy: Delineation of the electroclinical phenotype and treatment response

Cited by 139 publications

References 6 publications

Seizures Due to a KCNQ2 Mutation: Treatment with Vitamin B6

Seizures Due to a KCNQ2 Mutation: Treatment with Vitamin B6

A novel KCNQ3 mutation in familial epilepsy with focal seizures and intellectual disability

A Distinctive Ictal Amplitude-Integrated Electroencephalography Pattern in Newborns with Neonatal Epilepsy Associated with <b><i>KCNQ2</i></b> Mutations

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