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Dravet syndrome and Dravet syndrome-like phenotype: a systematic review of the SCN1A and PCDH19 variants

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Abstract

Dravet syndrome (DS) is a rare and severe epileptic syndrome of childhood with prevalence between 1/22,000 and 1/49,900 of live births. Approximately 80% of patients with this syndrome present SCN1A pathogenic variants, which encodes an alpha subunit of a neural voltage-dependent sodium channel. There is a correlation between PCDH19 pathogenic variants, encodes the protocadherin 19, and a similar disease to DS known as DS-like phenotype. The present review aims to clarify the differences between DS and DS-like phenotype according to the SCN1A and PCDH19 variants. A systematic review was conducted in PubMed and Virtual Health Library (VHL) databases, using “Dravet Syndrome” and “Severe Myoclonic Epilepsy in Infancy (SMEI)” search words, selecting cohort of studies published in journal with impact factor of two or greater. The systematic review was according to the Preferred Reporting Items for Systematic Review and Meta-Analysis recommendations. Nineteen studies were included in the present review, and a significant proportion of patients with DS-carrying SCN1A was greater than patients with DS-like phenotype-harboring PCDH19 variants (76.6% versus 23.4%). When clinical and genetic data were correlated, autism was predominantly observed in patients with DS-like-carrying PCDH19 variants compared to SCN1A variant carriers (62.5% versus 37.5%, respectively, P-value = 0.044, P-value corrected = 0.198). In addition, it was noticed a significant predisposition to hyperthermia during epilepsy crisis in individuals carrying PCDH19 variants (P-value = 0.003; P-value corrected = 0.027). The present review is the first to point out differences between the DS and DS-like phenotype according to the SCN1A and PCDH19 variants.

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Author information

Author notes

  1. Ana Carla Mondek Rampazzo and Rafael Rodrigues Pinheiro dos Santos with the same contribution to the article.

Authors and Affiliations

  1. Pontifical Catholic University of Paraná, 485 Jockei Club Ave., Londrina, Paraná, 86072-360, Brazil

    Ana Carla Mondek Rampazzo, Rafael Rodrigues Pinheiro dos Santos & Fernando Arfux Maluf

  2. Neurophysiology Clinic, Clinics Hospital, São Paulo, São Paulo, Brazil

    Renata Faria Simm

  3. Laboratory of Cellular and Molecular Biology of Tumors and Bioactive Compounds and Laboratory of Human and Medical Genetics, São Francisco University, Bragança Paulista, São Paulo, Brazil

    Fernando Augusto Lima Marson, Manoela Marques Ortega & Paulo Henrique Pires de Aguiar

  4. Department of Neurosurgery, Postgraduate Program in Health Sciences, State Public Medical Assistance Institute, Department of Neurosurgery, Santa Paula Hospital, São Paulo, São Paulo, Brazil

    Paulo Henrique Pires de Aguiar

  5. Research and Innovation Department of the Cellular and Molecular Biology Laboratory of the ABC, School of Medicine, Santo André, São Paulo, São Paulo, Brazil

    Paulo Henrique Pires de Aguiar

  6. Department of Neurology, School of Medicine, Pontifical Catholic University of São Paulo, São Paulo, Brazil

    Paulo Henrique Pires de Aguiar

Authors
  1. Ana Carla Mondek Rampazzo
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  2. Rafael Rodrigues Pinheiro dos Santos
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  3. Fernando Arfux Maluf
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  4. Renata Faria Simm
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  5. Fernando Augusto Lima Marson
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  6. Manoela Marques Ortega
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  7. Paulo Henrique Pires de Aguiar
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Contributions

A.C.M.R. and R.R.P.S. collected data and wrote the manuscript. F.A.M. collected data. R.F.S. reviewed clinical data. F.A.L.M. did statistical analysis. M.M.O. and P.H.P.A. guided the study and reviewed the manuscript.

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Correspondence to Ana Carla Mondek Rampazzo.

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Rampazzo, A.C.M., dos Santos, R.R.P., Maluf, F.A. et al. Dravet syndrome and Dravet syndrome-like phenotype: a systematic review of the SCN1A and PCDH19 variants. Neurogenetics 22, 105–115 (2021). https://doi.org/10.1007/s10048-021-00644-7

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  • DOI: https://doi.org/10.1007/s10048-021-00644-7

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