Dravet Syndrome − experience of a Neuropediatric Unit

Authors

  • Rafael Costa Figueiredo Department of Pediatrics, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto
  • Ruben Rocha Neuropediatrics Unit, Department of Pediatrics, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto
  • Cristina Freitas Baptista Department of Pediatrics, Centro Hospitalar Trás-Os-Montes e Alto Douro
  • Manuela Santos Neuropediatrics Unit, Department of Pediatrics, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto
  • Sónia Figueiroa Neuropediatrics Unit, Department of Pediatrics, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto
  • Inês Carrilho Neuropediatrics Unit, Department of Pediatrics, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto
  • Teresa Temudo Neuropediatrics Unit, Department of Pediatrics, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto

Keywords:

Dravet syndrome, Dravet Syndrome; SCN1A gene; Severe myoclonic epilepsy in infancy., severe myoclonic epilepsy in infancy

Abstract

Introduction: Dravet syndrome (DS) is a rare and complex genetic epilepsy syndrome. The first seizures are generally induced by fever in the first year of life of a previously healthy child, and the condition is typically associated with impaired psychomotor development.

The authors present a clinical review of DS patients followed at a Neuropediatric Unit of a level III Pediatric Hospital.

Material and methods: Retrospective study of pediatric patients with DS followed at a Neuropediatric Unit between 2001 and 2019.

Results: Twenty-two patients were diagnosed and followed in this institution. The median (interquartile range [IQR]) age at first seizure was 4.5 (4-5.75) months, which was described as generalized tonic-clonic, focal seizure, or focal to bilateral tonic-clonic seizure, and 95% of patients had fever during this first episode. Neuroimaging and first electroencephalogram (EEG) were normal in all patients. SCN1A gene mutations were detected in 21 (95%) patients. All patients underwent multiple antiepileptic drug (AED) regimens. Psychomotor development was delayed in 20 (91%) patients, and 13 (59%) presented ataxia. At the end of follow-up, the median (IQR) age was 19 (8-23) years, with no reported deaths.

Discussion: The characteristics of the first DS seizures are crucial for diagnosis, which can be supported by genetic sequencing, with most patients presenting an SCN1A gene mutation. Neuroimaging and EEG are typically normal at disease onset, but most patients present EEG abnormalities over time. Seizure management can be challenging, requiring a combination of multiple AEDs.

Conclusion: DS is a progressive disease associated with poor cognitive and motor skill outcomes, resulting in great morbidity. Early diagnosis can help avoid unnecessary studies, optimize the therapeutic strategy, allow genetic counseling, and improve long-term outcomes.

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References

Dravet C, Guerrini R. Topics in epilepsy: Dravet syndrome, 3rd ed, John Libbey Eurotext, 2011. p119.

Brunklaus A, Ellis R, Reavey E, Forbes GH, Zuberi SM. Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome. Brain. 2012;135(8):2329–36.

Hurst DL. Epidemiology of Severe Myoclonic Epilepsy of Infancy. Epilepsia. 1990;31(4):397–400.

Wu YW, Sullivan J, McDaniel SS, Meisler MH, Walsh EM, Li SX, et al. Incidence of dravet syndrome in a US population. Pediatrics. 2015;136(5):e1310–5.

Dravet C. Dravet syndrome history. Dev Med Child Neurol. 2011;53(SUPPL. 2):1–6.

Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512–21.

Bureau M, Bernardina BD. Electroencephalographic characteristics of Dravet syndrome. Epilepsia. 2011;52(SUPPL. 2):13–23.

Zuberi SM, Brunklaus A, Birch R, Reavey E, Duncan J, Forbes GH. Genotype-phenotype associations in SCN1A-related epilepsies. Neurology. 2011 Feb 15;76(7):594-600.

Margherita Mancardi M, Striano P, Gennaro E, Madia F, Paravidino R, Scapolan S, et al. Familial occurrence of febrile seizures and epilepsy in severe myoclonic epilepsy of infancy (SMEI) patients with SCN1A mutations. Epilepsia. 2006;47(10):1629–35.

Wirrell EC, Laux L, Donner E, Jette N, Knupp K, Meskis MA, et al. Optimizing the Diagnosis and Management of Dravet Syndrome: Recommendations From a North American Consensus Panel. Pediatr Neurol [Internet]. 2017;68:18-34.e3.

Caraballo RH, Fejerman N. Dravet syndrome: A study of 53 patients. Epilepsy Res. 2006;70(SUPPL.)1:S231-8.

Rosander C, Hallböök T. Dravet syndrome in Sweden: A population-based study. Dev Med Child Neurol. 2015;57(7):628–33.

Anwar A, Saleem S, Patel UK, Arumaithurai K, Malik P. Dravet Syndrome: An Overview. Cureus. 2019;11(6):1–11.

Djémié T, Weckhuysen S, Von Spiczak S, Carvill GL, Jaehn J, Anttonen AK, et al. Pitfalls in genetic testing: The story of missed SCN1A mutations. Mol Genet Genomic Med. 2016;4(4):457–64.

Wheless JW, Fulton SP, Mudigoudar BD. Dravet Syndrome: A Review of Current Management. Pediatr Neurol [Internet]. 2020;107:28–40.

Striano P, Mancardi MM, Biancheri R, Madia F, Gennaro E, Paravidino R, et al. Brain MRI findings in severe myoclonic epilepsy in infancy and genotype-phenotype correlations. Epilepsia. 2007;48(6):1092–6.

Siegler Z, Barsi P, Neuwirth M, Jerney J, Kassay M, Janszky J, et al. Hippocampal sclerosis in severe myoclonic epilepsy in infancy: A retrospective MRI study. Epilepsia. 2005;46(5):704–8.

Ziobro J, Eschbach K, Sullivan JE, Knupp KG. Current Treatment Strategies and Future Treatment Options for Dravet Syndrome. Curr Treat Options Neurol. 2018 Oct 13;20(12):52.

Specchio N, Balestri M, Trivisano M, Japaridze N, Striano P, Carotenuto A, et al. Electroencephalographic features in Dravet syndrome: Five-year follow-up study in 22 patients. J Child Neurol. 2012;27(4):439–44.

Cross JH, Caraballo RH, Nabbout R, Vigevano F, Guerrini R, Lagae L. Dravet syndrome: Treatment options and management of prolonged seizures. Epilepsia. 2019;60(S3):S39–48.

Kröll-Seger J, Portilla P, Dulac O, Chiron C. Topiramate in the treatment of highly refractory patients with dravet syndrome. Neuropediatrics. 2006;37(6):325–9.

Fariba K, Saadabadi A. Topiramate. [Updated 2020 Mar 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020.

Wheless JW, Fulton SP, Mudigoudar BD. Dravet Syndrome: A Review of Current Management. Pediatr Neurol [Internet]. 2020;107:28–40.

Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al. Trial of cannabidiol for drug-resistant seizures in the dravet syndrome. N Engl J Med. 2017;376(21):2011–20.

Lagae L, Sullivan J, Knupp K, Laux L, Polster T, Nikanorova M, et al. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial. Lancet [Internet]. 2019;394(10216):2243–54.

Nabbout R, Mistry A, Zuberi S, Villeneuve N, Gil-Nagel A, Sanchez-Carpintero R, et al. Fenfluramine for Treatment-Resistant Seizures in Patients with Dravet Syndrome Receiving Stiripentol-Inclusive Regimens: A Randomized Clinical Trial. JAMA Neurol. 2020;77(3):300–8.

Hsiao J, Yuan TY, Tsai MS, Lu CY, Lin YC, Lee ML, et al. Upregulation of Haploinsufficient Gene Expression in the Brain by Targeting a Long Non-coding RNA Improves Seizure Phenotype in a Model of Dravet Syndrome. EBioMedicine. 2016;9:257–77.

Ragona F, Brazzo D, Giorgi I De, Morbi M, Freri E, Teutonico F, et al. Dravet syndrome: Early clinical manifestations and cognitive outcome in 37 Italian patients. Brain Dev [Internet]. 2010;32(1):71–7.

Skluzacek J V., Watts KP, Parsy O, Wical B, Camfield P. Dravet syndrome and parent associations: The IDEA League experience with comorbid conditions, mortality, management, adaptation, and grief. Epilepsia. 2011;52(SUPPL. 2):95–101.

Cooper MS, Mcintosh A, Crompton DE, McMahon JM, Schneider A, Farrell K, et al. Mortality in Dravet syndrome. Epilepsy Res [Internet]. 2016;128:43–7.

Shmuely S, Sisodiya SM, Gunning WB, Sander JW, Thijs RD. Mortality in Dravet syndrome: A review. Epilepsy Behav [Internet]. 2016;64:69–74.

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Published

2021-12-27

How to Cite

1.
Figueiredo RC, Rocha R, Freitas Baptista C, Santos M, Figueiroa S, Carrilho I, Temudo T. Dravet Syndrome − experience of a Neuropediatric Unit. REVNEC [Internet]. 2021Dec.27 [cited 2022Jan.24];30(4):213-8. Available from: https://revistas.rcaap.pt/nascercrescer/article/view/21347

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