Download PDF
Journal of Pediatric Epilepsy 2023; 12(03): 091-097
DOI: 10.1055/s-0042-1758660
Original Article

A Retrospective Study of the Profile and Outcome of Children with Dravet Syndrome in a Tertiary Care Hospital of Southern India

Bidisha Banerjee 
1   Department of Paediatric Neurology, Manipal Hospital, Bangalore, Karnataka, India
,
Sameeta M. Prabhu 
1   Department of Paediatric Neurology, Manipal Hospital, Bangalore, Karnataka, India
,
Gowthami Lagudu
2   Department of Paediatrics, Manipal Hospital, Bangalore, Karnataka, India
,
Mitesh Shetty
3   Department of Genetics, Manipal Hospital, Bangalore, Karnataka, India
,
Sridevi Hegde
3   Department of Genetics, Manipal Hospital, Bangalore, Karnataka, India
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

Objective Dravet syndrome (DS) is an epileptic syndrome that shares similarities with febrile seizures (FS), especially before 1 year of age, making it challenging to differentiate the two. We describe the profile of DS, with emphasis on the first year of life that can aid in early diagnosis.

Methods The clinical, investigative, treatment, and outcome profiles of DS patients presenting to the outpatient department (OPD) between October 2016 and December 2021 in a single tertiary care center in South India were analyzed.

Results Seventeen children were studied, with median age at presentation of 30 (interquartile range [IQR] 10, 47) months. The median age at seizure onset was 5 (IQR 3, 6) months. First seizure semiology were generalized tonic-clonic (GTCS) (35.3%), focal (52.9%), and myoclonic (11.8%). Fever preceding first seizure was seen in 76.5%. Status epilepticus (SE; ≥30 minutes) and prolonged seizures (>10 minutes) were seen in 41.2% each, and >5 seizures were seen in 82.4% in the first year of life. The most frequent subsequent seizure types were focal seizures (76.5%) and GTCS (76.5%). Other seizure triggers included vaccination (52.9%), light (17.6%), and Hot-bath (5.8%). Delayed developmental milestones for age were found in 52.9% at diagnosis. Magnetic resonance imaging (MRI) brain and electroencephalogram were normal in 76.4% each. Pathogenic/likely pathogenic variants in SCN1A gene were seen in 64.7%. Average of 3.9 anti-seizure medications were used. After optimization of treatment seizure frequency reduced in 40% and 4/15 (26.6%) had SE.

Conclusion In addition to characteristic clinical profile of DS we observed atypical presentations: an earlier age of seizure onset and afebrile seizure at onset. Delayed diagnosis was noted. Seizure control improved and SE reduced on optimal treatment.

Keywords

Dravet syndrome - infancy - epileptic syndrome - drug refractory - SCN1A


Publication History

Received: 13 June 2022

Accepted: 25 September 2022

Article published online:
21 November 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Rosander C, Hallböök T. Dravet syndrome in Sweden: a population-based study. Dev Med Child Neurol 2015; 57 (07) 628-633
    CrossrefPubMedGoogle Scholar
  • 2 Hattori J, Ouchida M, Ono J. et al. A screening test for the prediction of Dravet syndrome before one year of age. Epilepsia 2008; 49 (04) 626-633
    CrossrefPubMedGoogle Scholar
  • 3 Dravet Syndrome - NORD (National Organization for Rare Disorders). NORD (National Organization for Rare Disorders). 2022 . Accessed May 05, 2022, at: https://rarediseases.org/rare-diseases/dravet-syndrome-spectrum/
    PubMedGoogle Scholar
  • 4 Li W, Schneider AL, Scheffer IE. Defining Dravet syndrome: an essential pre-requisite for precision medicine trials. Epilepsia 2021; 62 (09) 2205-2217
    CrossrefPubMedGoogle Scholar
  • 5 Ragona F, Brazzo D, De Giorgi I. et al. Dravet syndrome: early clinical manifestations and cognitive outcome in 37 Italian patients. Brain Dev 2010; 32 (01) 71-77
    CrossrefPubMedGoogle Scholar
  • 6 Petrelli C, Passamonti C, Cesaroni E. et al. Early clinical features in Dravet syndrome patients with and without SCN1A mutations. Epilepsy Res 2012; 99 (1-2): 21-27
    CrossrefPubMedGoogle Scholar
  • 7 Cetica V, Chiari S, Mei D. et al. Clinical and genetic factors predicting Dravet syndrome in infants with SCN1A mutations. Neurology 2017; 88 (11) 1037-1044
    CrossrefPubMedGoogle Scholar
  • 8 Zuberi SM, Wirrell E, Yozawitz E. et al. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia 2022; 63 (06) 1349-1397
    CrossrefPubMedGoogle Scholar
  • 9 Fisher RS, Cross JH, French JA. et al. Operational classification of seizure types by the International League against epilepsy: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017; 58 (04) 522-530
    CrossrefPubMedGoogle Scholar
  • 10 Miller DT, Lee K, Chung WK. et al; ACMG Secondary Findings Working Group. ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2021; 23 (08) 1381-1390
    CrossrefPubMedGoogle Scholar
  • 11 Dravet C. The core Dravet syndrome phenotype. Epilepsia 2011; 52 (Suppl. 02) 3-9
    CrossrefPubMedGoogle Scholar
  • 12 Harkin LA, McMahon JM, Iona X. et al; Infantile Epileptic Encephalopathy Referral Consortium. The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain 2007; 130 (Pt 3): 843-852
    CrossrefPubMedGoogle Scholar
  • 13 Bremer A, Lossius MI, Nakken KO. Dravet syndrome—considerable delay in making the diagnosis. Acta Neurol Scand 2012; 125 (05) 359-362
    CrossrefPubMedGoogle Scholar
  • 14 McIntosh AM, McMahon J, Dibbens LM. et al. Effects of vaccination on onset and outcome of Dravet syndrome: a retrospective study. Lancet Neurol 2010; 9 (06) 592-598
    CrossrefPubMedGoogle Scholar
  • 15 Catterall WA. Dravet syndrome: a sodium channel interneuronopathy. Curr Opin Physiol 2018; 2: 42-50
    CrossrefPubMedGoogle Scholar
  • 16 Striano P, Mancardi MM, Biancheri R. et al. Brain MRI findings in severe myoclonic epilepsy in infancy and genotype-phenotype correlations. Epilepsia 2007; 48 (06) 1092-1096
    CrossrefPubMedGoogle Scholar
  • 17 Scheffer IE, Zhang YH, Jansen FE, Dibbens L. Dravet syndrome or genetic (generalized) epilepsy with febrile seizures plus?. Brain Dev 2009; 31 (05) 394-400
    CrossrefPubMedGoogle Scholar
  • 18 Steel D, Symonds JD, Zuberi SM, Brunklaus A. Dravet syndrome and its mimics: Beyond SCN1A. Epilepsia 2017; 58 (11) 1807-1816
    CrossrefPubMedGoogle Scholar
  • 19 Marini C, Scheffer IE, Nabbout R. et al. SCN1A duplications and deletions detected in Dravet syndrome: implications for molecular diagnosis. Epilepsia 2009; 50 (07) 1670-1678
    CrossrefPubMedGoogle Scholar
  • 20 Mulley JC, Scheffer IE, Petrou S, Dibbens LM, Berkovic SF, Harkin LA. SCN1A mutations and epilepsy. Hum Mutat 2005; 25 (06) 535-542
    CrossrefPubMedGoogle Scholar
  • 21 Sun H, Zhang Y, Liu X. et al. Analysis of SCN1A mutation and parental origin in patients with Dravet syndrome. J Hum Genet 2010; 55 (07) 421-427
    CrossrefPubMedGoogle Scholar
  • 22 Depienne C, Trouillard O, Saint-Martin C. et al. Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients. J Med Genet 2009; 46 (03) 183-191
    CrossrefPubMedGoogle Scholar
  • 23 Cross JH, Caraballo RH, Nabbout R, Vigevano F, Guerrini R, Lagae L. Dravet syndrome: treatment options and management of prolonged seizures. Epilepsia 2019; 60 (Suppl. 03) S39-S48
    PubMedGoogle Scholar
  • 24 Takayama R, Fujiwara T, Shigematsu H. et al. Long-term course of Dravet syndrome: a study from an epilepsy center in Japan. Epilepsia 2014; 55 (04) 528-538
    CrossrefPubMedGoogle Scholar
  • 25 Fujiwara T, Watanabe M, Takahashi Y, Higashi T, Yagi K, Seino M. Long-term course of childhood epilepsy with intractable grand mal seizures. Jpn J Psychiatry Neurol 1992; 46 (02) 297-302
    PubMedGoogle Scholar
  • 26 Kapoor D, Anand A, Sharma S. et al. Dravet syndrome: a case series. Indian J Pediatr 2021; 88 (01) 82-82
    CrossrefPubMedGoogle Scholar
  • 27 Wirrell EC, Laux L, Franz DN. et al. Stiripentol in Dravet syndrome: results of a retrospective U.S. study. Epilepsia 2013; 54 (09) 1595-1604
    CrossrefPubMedGoogle Scholar
  • 28 Gulati S, Sinha R, Madaan P. Ethical, social, and economic challenges in managing a child with Dravet syndrome in a developing country. J Pediatr Epilepsy 2020; 9 (03) 94-96
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Lattanzi S, Brigo F, Trinka E. et al. Efficacy and safety of cannabidiol in epilepsy: a systematic review and meta-analysis. Drugs 2018; 78 (17) 1791-1804
    CrossrefPubMedGoogle Scholar
  • 30 Lattanzi S, Trinka E, Striano P. et al. Cannabidiol efficacy and clobazam status: a systematic review and meta-analysis. Epilepsia 2020; 61 (06) 1090-1098
    CrossrefPubMedGoogle Scholar
  • 31 Simon K, Sheckley H, Anderson CL, Liu Z, Carney PR. A review of fenfluramine for the treatment of Dravet syndrome patients. Curr Res Pharmacol Drug Discov 2021; 3: 100078
    CrossrefPubMedGoogle Scholar