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Cardiac phenotypic spectrum of KCNT1 mutations

Published online by Cambridge University Press:  04 September 2020

Utkarsh Kohli Open the ORCID record for Utkarsh Kohli [Opens in a new window] ,
Chitra Ravishankar  and
Douglas Nordli
Utkarsh Kohli*
Affiliation:
Division of Pediatric Cardiology, Department of Pediatrics, Comer Children’s Hospital and Pritzker School of Medicine of the University of Chicago, Chicago, IL, USA
Chitra Ravishankar
Affiliation:
Division of Cardiology, Department of Pediatrics, The Children’s Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
Douglas Nordli
Affiliation:
Section of Child Neurology, Department of Pediatrics, Pritzker School of Medicine of the University of Chicago, Chicago, IL, USA
*
Address for correspondence: Utkarsh Kohli, Assistant Professor of Pediatrics, Section of Pediatric Cardiology, Department of Pediatrics, Comer Children’s Hospital and the Pritzker School of Medicine of University of Chicago, 5841 S Maryland Ave., Chicago, IL60637, USA. Tel: +1 773 702 6172; Fax: +1 773 702 2319. Email: [email protected]/[email protected]
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Abstract

We report a 10-month-old girl with KCNT1 (c1420C > T; p. Arg474Cys, R474C) mutation-associated epileptic encephalopathy, systemic-to-pulmonary artery “collateralopathy”, and intermittent QTc prolongation. Spontaneous regression of systemic-to-pulmonary artery collateral-mediated left heart dilation was noted in this patient, a finding which was ominous as it heralded the onset of severe pulmonary hypertension. The structural and electrical phenotypic features of KCNT1 mutation-associated heart disease, including the novel findings noted in our patient, are discussed in detail.

Keywords

KCNT1 mutationssystemic-to-pulmonary artery collateralsprolonged QTcleft heart enlargementpulmonary hypertensionsudden deathheart failure
Type
Brief Report
Information
Cardiology in the Young , Volume 30 , Issue 12 , December 2020 , pp. 1935 - 1939
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Copyright
© The Author(s), 2020. Published by Cambridge University Press

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References

Barcia, G, Fleming, MR, Deligniere, A, et al. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nature Genetics 2012; 44: 1255–1259. doi: 10.1038/ng.2441 CrossRefGoogle ScholarPubMed
Bhattacharjee, A, Gan, L, Kaczmarek, LK. Localization of the Slack potassium channel in the rat central nervous system. J Comp Neurol 2002; 454: 241–254.CrossRefGoogle ScholarPubMed
de Los Angeles Tejada, M, Stolpe, K, Meinild, AK, Klaerke, DA. Clofilium inhibits slick and slack potassium channels. Biologics 2012; 6: 465–470. doi: 10.2147/BTT.S33827.Google ScholarPubMed
Lim, CX, Ricos, MG, Dibbens, LM, Heron, SE. KCNT1 mutations in seizure disorders: the phenotypic spectrum and functional effects. J Med Genet 2016; 53: 217–225. doi 10.1136/jmedgenet-2015-103508.CrossRefGoogle ScholarPubMed
Ohba, C, Kato, M, Takahashi, N, et al. De novo KCNT1 mutations in early-onset epileptic encephalopathy. Epilepsia 2015; 56: e121–e128. doi: 10.1111/epi.13072.CrossRefGoogle ScholarPubMed
Shimada, S, Hirano, Y, Ito, S, et al. A novel KCNT1 mutation in a Japanese patient with epilepsy of infancy with migrating focal seizures. Hum Genome Var 2014; 1: 14027. doi: 10.1038/hgv.2014.27.CrossRefGoogle Scholar
Kuchenbuch, M, Barcia, G, Chemaly, N, et al. KCNT1 epilepsy with migrating focal seizures shows a temporal sequence with poor outcome, high mortality and SUDEP. Brain 2019; 142: 2996–3008. doi: 10.1093/brain/awz240.CrossRefGoogle Scholar
Kawasaki, Y, Kuki, I, Ehara, E, et al. Three cases of KCNT1 mutations: malignant migrating partial seizures in infancy with massive systemic to pulmonary collateral arteries. J Pediatr 2017; 191: 270–274. doi: 10.1016/j.jpeds.2017.08.057.CrossRefGoogle ScholarPubMed
Stenson, PD, Mort, M, Ball, EV, Shaw, K, Phillips, A, Cooper, DN. The human gene mutation database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Hum Gent 2014; 133: 1–9.CrossRefGoogle ScholarPubMed
McTague, A, Nair, U, Malhotra, S, et al. Clinical and molecular characterization of KCNT1-related severe early-onset epilepsy. Neurology 2018; 1: e55-e66. doi: 10.1212/WNL.0000000000004762.CrossRefGoogle Scholar
Juang, JM, Lu, TP, Lai, LC, et al. Disease-targeted sequencing of ion channel genes identifies de novo mutations in patients with non-familial Brugada syndrome. Sci Rep 2014; 4: 6733. doi: 10.1038/srep06733.CrossRefGoogle ScholarPubMed
Barcia, G, Chemaly, N, Kuchenbuch, M, et al. Epilepsy with migrating focal seizures: KCNT1 mutation hotspots and phenotype variability. Neurol Genet 2019; 5: e363. doi: 10.1212/NXG.0000000000000363.CrossRefGoogle ScholarPubMed
Møller, RS, Heron, SE, Larsen, LH, et al. Mutations in KCNT1 cause a spectrum of focal epilepsies. Epilepsia 2015; 56: e114–20. doi: 10.1111/epi.13071.CrossRefGoogle Scholar
Milligan, CJ, Li, M, Gazina, EV, et al. KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine. Ann Neurol 2014; 75: 581–90. doi: 10.1002/ana.24128.CrossRefGoogle ScholarPubMed
Fitzgerald, MP, Fiannacca, M, Smith, DM, et al. Treatment responsiveness in KCNT1-related epilepsy. Neurotherapeutics 2019; 6: 848–857. doi: 10.1007/s13311-019-00739-y.CrossRefGoogle Scholar
Yoshitomi, S, Takahashi, Y, Yamaguchi, T, et al. Quinidine therapy and therapeutic drug monitoring in four patients with KCNT1 mutations. Epileptic Disord 2019; 21: 48–54. doi: 10.1684/epd.2019.1026.Google ScholarPubMed
Numis, AL, Nair, U, Datta, AN, et al. Lack of response to quinidine in KCNT1-related neonatal epilepsy. Epilepsia 2018; 59: 1889–1898. doi: 10.1111/epi.14551.CrossRefGoogle ScholarPubMed