Journal of Pediatric Neurology 2016; 14(04): 151-155
DOI: 10.1055/s-0036-1593744
Case Report
Georg Thieme Verlag KG Stuttgart · New York

Genetic Association with Ictal Cardiorespiratory Phenomena: SCN8A Case Series

Ammar Hussain
1   Department of Child Neurology, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States
,
Syndi Seinfeld
1   Department of Child Neurology, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States
,
Lawrence Morton
1   Department of Child Neurology, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States
› Institutsangaben
Weitere Informationen

Publikationsverlauf

23. Mai 2016

06. September 2016

Publikationsdatum:
21. Oktober 2016 (online)

Abstract

Increased availability of genetic testing has led to identification of expanding SCN8A phenotypic spectrum ranging from early-infantile epileptic encephalopathy (EIEE) to developmental and cognitive disabilities, movement disorders, and a possible high incidence of sudden unexplained death in epilepsy patients (SUDEP). Children with SCN8A mutations may also have dysfunction of cardiac voltage gated sodium channels, resulting in ictal cardiac symptoms with associated respiratory distress. We report a case series of two patients with de novo SCN8A mutation. These patients presented with recurrent tonic seizures at 4 and 6 months of age, along with ictal bradycardia and asystole respectively. Interictally both patients had normal EEG and cardiac evaluation. The antiepileptic drug treatment choice was made prior to known genetic abnormality, with resultant decrease in seizure frequency and severity of cardiorespiratory symptoms in both patients. The association of SCN8A mutation–related rare epilepsy with ictal cardiac symptoms has not been well described in the literature. The association of ictal cardiac phenomena with this mutation is important in patient treatment, family education, and risk of complications such as SUDEP. The role of SCN8A in the mechanism of SUDEP requires future studies.

 
  • References

  • 1 de Kovel CG, Meisler MH, Brilstra EH , et al. Characterization of a de novo SCN8A mutation in a patient with epileptic encephalopathy. Epilepsy Res 2014; 108 (9) 1511-1518
  • 2 Catterall WA. Voltage-gated sodium channels at 60: structure, function and pathophysiology. J Physiol 2012; 590 (11) 2577-2589
  • 3 Veeramah KR, O'Brien JE, Meisler MH , et al. De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP. Am J Hum Genet 2012; 90 (3) 502-510
  • 4 Duplyakov D, Golovina G, Lyukshina N, Surkova E, Elger CE, Surges R. Syncope, seizure-induced bradycardia and asystole: two cases and review of clinical and pathophysiological features. Seizure 2014; 23 (7) 506-511
  • 5 Wagnon JL, Meisler MH. Recurrent and non-recurrent mutations of SCN8A in epileptic encephalopathy. Front Neurol 2015; 6: 104
  • 6 Wagnon JL, Barker BS, Hounshell JA , et al. Pathogenic mechanism of recurrent mutations of SCN8A in epileptic encephalopathy. Ann Clin Transl Neurol 2015; 3 (2) 114-123
  • 7 Trudeau MM, Dalton JC, Day JW, Ranum LP, Meisler MH. Heterozygosity for a protein truncation mutation of sodium channel SCN8A in a patient with cerebellar atrophy, ataxia, and mental retardation. J Med Genet 2006; 43 (6) 527-530
  • 8 Noujaim SF, Kaur K, Milstein M , et al. A null mutation of the neuronal sodium channel NaV1.6 disrupts action potential propagation and excitation-contraction coupling in the mouse heart. FASEB J 2012; 26 (1) 63-72
  • 9 O'Brien JE, Meisler MH. Sodium channel SCN8A (Nav1.6): properties and de novo mutations in epileptic encephalopathy and intellectual disability. Front Genet 2013; 4: 213
  • 10 Vaher U, Nõukas M, Nikopensius T , et al. De novo SCN8A mutation identified by whole-exome sequencing in a boy with neonatal epileptic encephalopathy, multiple congenital anomalies, and movement disorders. J Child Neurol 2014; 29 (12) NP202-NP206
  • 11 Kong W, Zhang Y, Gao Y , et al. SCN8A mutations in Chinese children with early onset epilepsy and intellectual disability. Epilepsia 2015; 56 (3) 431-438
  • 12 Larsen J, Carvill GL, Gardella E , et al; EuroEPINOMICS RES Consortium CRP. The phenotypic spectrum of SCN8A encephalopathy. Neurology 2015; 84 (5) 480-489
  • 13 Estacion M, O'Brien JE, Conravey A , et al. A novel de novo mutation of SCN8A (Nav1.6) with enhanced channel activation in a child with epileptic encephalopathy. Neurobiol Dis 2014; 69: 117-123
  • 14 Britton JW, Ghearing GR, Benarroch EE, Cascino GD. The ictal bradycardia syndrome: localization and lateralization. Epilepsia 2006; 47 (4) 737-744
  • 15 Barker BS, Ottolini M, Wagnon JL, Hollander RM, Meisler MH, Patel MK. The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin. Epilepsia 2016; 57 (9) 1458-1466
  • 16 Meisler MH, Helman G, Hammer MF , et al. SCN8A encephalopathy: research progress and prospects. Epilepsia 2016; 57 (7) 1027-1035
  • 17 Uusimaa J, Gowda V, McShane A , et al. Prospective study of POLG mutations presenting in children with intractable epilepsy: prevalence and clinical features. Epilepsia 2013; 54 (6) 1002-1011
  • 18 Poduri A. The expanding SCN8A-related epilepsy phenotype. Epilepsy Curr 2015; 15 (6) 333-334
  • 19 Ohba C, Kato M, Takahashi S , et al. Early onset epileptic encephalopathy caused by de novo SCN8A mutations. Epilepsia 2014; 55 (7) 994-1000
  • 20 Blanchard MG, Willemsen MH, Walker JB , et al. De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy. J Med Genet 2015; 52 (5) 330-337
  • 21 Singh R, Jayapal S, Goyal S, Jungbluth H, Lascelles K. Early-onset movement disorder and epileptic encephalopathy due to de novo dominant SCN8A mutation. Seizure 2015; 26: 69-71
  • 22 Boerma RS, Braun KP, van den Broek MPH , et al. Remarkable phenytoin sensitivity in 4 children with SCN8A-related epilepsy: a molecular neuropharmacological approach. Neurotherapeutics 2016; 13 (1) 192-197
  • 23 Horvath GA, Demos M, Shyr C , et al. Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: a potential treatment target?. Mol Genet Metab 2016; 117 (1) 42-48