Neonatal tremor episodes and hyperekplexia-like presentation at onset in a child with SCN8A developmental and epileptic encephalopathy
Corresponding Author
Linda Pons
Service de Génétique, Laboratoire de Cytogénétique Constitutionnelle, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon
Lyon Neuroscience Research Centre (CRNL), GENDEV team, CNRS UMR 5292, INSERM U1028, UCBL1
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Correspondence: Dr Linda Pons Service de Génétique, Laboratoire de Cytogénétique Constitutionnelle, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69677 Bron Cedex, France <[email protected]>Search for more papers by this authorGaëtan Lesca
Service de Génétique, Laboratoire de Cytogénétique Constitutionnelle, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon
Lyon Neuroscience Research Centre (CRNL), GENDEV team, CNRS UMR 5292, INSERM U1028, UCBL1
Université Claude Bernard Lyon 1, Lyon
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Search for more papers by this authorDamien Sanlaville
Service de Génétique, Laboratoire de Cytogénétique Constitutionnelle, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon
Lyon Neuroscience Research Centre (CRNL), GENDEV team, CNRS UMR 5292, INSERM U1028, UCBL1
Université Claude Bernard Lyon 1, Lyon
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Search for more papers by this authorNicolas Chatron
Service de Génétique, Laboratoire de Cytogénétique Constitutionnelle, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon
Lyon Neuroscience Research Centre (CRNL), GENDEV team, CNRS UMR 5292, INSERM U1028, UCBL1
Université Claude Bernard Lyon 1, Lyon
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Search for more papers by this authorAudrey Labalme
Service de Génétique, Laboratoire de Cytogénétique Constitutionnelle, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Search for more papers by this authorVéronique Manel
Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology, HFME, University Hospitals of Lyon (HCL), Member of the European Reference Network EPICARE, Lyon
Search for more papers by this authorAlexis Arzimanoglou
Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology, HFME, University Hospitals of Lyon (HCL), Member of the European Reference Network EPICARE, Lyon
Lyon Neuroscience Research Centre (CRNL), DYCOG team, INSERM U1028; CNRS UMR 5292, Lyon
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Search for more papers by this authorJulitta de Bellescize
Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology, HFME, University Hospitals of Lyon (HCL), Member of the European Reference Network EPICARE, Lyon
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Search for more papers by this authorLaurence Lion-François
Service de Neurologie Pédiatrique, HFME, Hospices Civils de Lyon
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Search for more papers by this authorCorresponding Author
Linda Pons
Service de Génétique, Laboratoire de Cytogénétique Constitutionnelle, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon
Lyon Neuroscience Research Centre (CRNL), GENDEV team, CNRS UMR 5292, INSERM U1028, UCBL1
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Correspondence: Dr Linda Pons Service de Génétique, Laboratoire de Cytogénétique Constitutionnelle, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, 59 Boulevard Pinel, 69677 Bron Cedex, France <[email protected]>Search for more papers by this authorGaëtan Lesca
Service de Génétique, Laboratoire de Cytogénétique Constitutionnelle, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon
Lyon Neuroscience Research Centre (CRNL), GENDEV team, CNRS UMR 5292, INSERM U1028, UCBL1
Université Claude Bernard Lyon 1, Lyon
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Search for more papers by this authorDamien Sanlaville
Service de Génétique, Laboratoire de Cytogénétique Constitutionnelle, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon
Lyon Neuroscience Research Centre (CRNL), GENDEV team, CNRS UMR 5292, INSERM U1028, UCBL1
Université Claude Bernard Lyon 1, Lyon
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Search for more papers by this authorNicolas Chatron
Service de Génétique, Laboratoire de Cytogénétique Constitutionnelle, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon
Lyon Neuroscience Research Centre (CRNL), GENDEV team, CNRS UMR 5292, INSERM U1028, UCBL1
Université Claude Bernard Lyon 1, Lyon
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Search for more papers by this authorAudrey Labalme
Service de Génétique, Laboratoire de Cytogénétique Constitutionnelle, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Search for more papers by this authorVéronique Manel
Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology, HFME, University Hospitals of Lyon (HCL), Member of the European Reference Network EPICARE, Lyon
Search for more papers by this authorAlexis Arzimanoglou
Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology, HFME, University Hospitals of Lyon (HCL), Member of the European Reference Network EPICARE, Lyon
Lyon Neuroscience Research Centre (CRNL), DYCOG team, INSERM U1028; CNRS UMR 5292, Lyon
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Search for more papers by this authorJulitta de Bellescize
Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology, HFME, University Hospitals of Lyon (HCL), Member of the European Reference Network EPICARE, Lyon
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Search for more papers by this authorLaurence Lion-François
Service de Neurologie Pédiatrique, HFME, Hospices Civils de Lyon
Centre de Référence des Épilepsies Rares (CReER)Maladies, HFME-HCL, Lyon, France
Search for more papers by this authorABSTRACT
SCN8A encephalopathy is a newly defined epileptic encephalopathy caused by de novo mutations of the SCN8A gene. We report herein a four-year-old boy presenting with severe non-epileptic abnormal movements, of possibly antenatal onset, progressively associated with pharmacoresistant epilepsy and regression, associated with a de novo heterozygous missense mutation of SCN8A. This case shows that paroxysmal non-epileptic episodes of severe tremor and hyperekplexia-like startles and a striking vegetative component can be the first early symptoms of severe SCN8A developmental and epileptic encephalopathy. Clinicians should be aware of these symptoms in order to avoid misdiagnosis and ensure early appropriate therapeutic management. [Published with video sequences on www.epilepticdisorders.com].
References
- Blanchard M.G., Willemsen M.H., Walker J.B., et al. De novo gain-of-function and loss-of-function mutations of in patients with intellectual disabilities and epilepsySCN8AJ Med Genet 2015; 52: 330–337
- Boerma R.S., Braun K.P., van den Broek M.P.H., et al. Remarkable phenytoin sensitivity in 4 children with SCN8A-related epilepsy: a molecular neuropharmacological approach. Neurotherapeutics 2016; 13: 192–197
- Brown P., Farmer S.F., Halliday D.M., Marsden J., Rosenberg J.R. Coherent cortical and muscle discharge in cortical myoclonus. Brain 1999; 122: 461–472
- Butler K.M., da Silva C., Shafir Y., et al. De novo and inherited epilepsy mutations detected by gene panel analysisSCN8AEpilepsy Res 2017; 129: 17–25
- Canafoglia L., Bugiani M., Uziel G., et al. Rhythmic cortical myoclonus in Niemann-Pick disease type C. Mov Disord 2006; 21: 1453–1456
- Dreissen Y.E.M., Tijssen M.A.J. The startle syndromes: physiology and treatment. Epilepsia 2012; 53: 3–11
- Dyment D.A., Tétreault M., Beaulieu C.L., et al. Whole-exome sequencing broadens the phenotypic spectrum of rare pediatric epilepsy: a retrospective study. Clin Genet 2015; 88: 34–40
- Epi4K Consortium Epilepsy Phenome/Genome Project, Allen AS, et al De novo mutations in epileptic encephalopathies. Nature 2013; 501: 217–221
- Larsen J., Carvill G.L., Gardella E., et al. The phenotypic spectrum of SCN8A encephalopathy. Neurology 2015; 84: 480–489
- Meisler M.H., Helman G., Hammer M.F., et al. SCN8A encephalopathy: research progress and prospects. Epilepsia 2016; 57: 1027–1035
- Mercimek-Mahmutoglu S., Patel J., Cordeiro D., et al. Diagnostic yield of genetic testing in epileptic encephalopathy in childhood. Epilepsia 2015; 56: 707–716
- Mignot C., Moutard M.-L., Trouillard O., et al. STXBP1-related encephalopathy presenting as infantile spasms and generalized tremor in three patients. Epilepsia 2011; 52: 1820–1827
- Mulkey S.B., 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: 436–445
- Ohba C., Kato M., Takahashi S., et al. Early onset epileptic encephalopathy caused by de novo mutationsSCN8AEpilepsia 2014; 55: 994–1000
- Panzica F., Canafoglia L., Franceschetti S., et al. Movement-activated myoclonus in genetically defined progressive myoclonic epilepsies: EEG-EMG relationship estimated using autoregressive models. Clin Neurophysiol 2003; 114: 1041–1052
- Rubboli G., Franceschetti S., Berkovic S.F., et al. Clinical and neurophysiologic features of progressive myoclonus epilepsy without renal failure caused by mutationsSCARB2Epilepsia 2011; 52: 2356–2363
- Scheffer I.E., Berkovic S., Capovilla G., et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017; 58: 512–551
- Singh R., Jayapal S., Goyal S., Jungbluth H., Lascelles K. Early-onset movement disorder and epileptic encephalopathy due to de novo dominant mutationSCN8ASeizure 2015; 26: 69–71
- Vaher U., Nõukas M., Nikopensius T., et al. De novo mutation identified by whole-exome sequencing in a boy with neonatal epileptic encephalopathy, multiple congenital anomalies, and movement disordersSCN8AJ Child Neurol 2014; 29: NP202–206
- Veeramah K.R., O’Brien J.E., Meisler M.H., et al. De novo pathogenic mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEPSCN8AAm J Hum Genet 2012; 90: 502–510
- Vigevano F., Di Capua M., Dalla Bernardina B. Startle disease: an avoidable cause of sudden infant death. Lancet 1989; 1: 216
- Walsh B.H., Baumer F.M., Bernson-Leung M.E., Lerou P., Peters J.M. Teaching video neuroimages: nonepileptic myoclonus in a neonate following severe hypoxic-ischemic injury. Neurology 2015; 84: e90
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