Dravet syndrome in South African infants: Tools for an early diagnosis

Alina I. Esterhuizen*, Heather C. Mefford, Rajkumar S. Ramesar, Shuyu Wang, Gemma L. Carvill, Jo M. Wilmshurst

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Purpose: Dravet syndrome (DS) is a well-described, severe genetic epileptic encephalopathy with an increased risk of SUDEP. The incidence and genetic architecture of DS in African patients is virtually unknown, largely due to lack of awareness and unavailability of genetic testing. The clinical benefits of the available precision medicine approaches to treatment emphasise the importance of an early, correct diagnosis. We investigated the genetic causes and clinical features of DS in South African children to develop protocols for early, cost-effective diagnosis in the local setting. Method: We selected 22 South African children provisionally diagnosed with clinical DS for targeted resequencing of DS-associated genes. We sought to identify the clinical features most strongly associated with SCN1A-related DS, using the DS risk score and clinical co-variates under various statistical models. Results: Disease-causing variants were identified in 10 of the 22 children: nine SCN1A and one PCDH19. Moreover, we showed that seizure onset before 6 months of age and a clinical DS risk score of >6 are highly predictive of SCN1A-associated DS. Clinical reassessment resulted in a revised diagnosis in 10 of the 12 variant-negative children. Conclusion: This first genetic study of DS in Africa confirms that de novo SCN1A variants underlie disease in the majority of South African patients. Affirming the predictive value of seizure onset before 6 months of age and a clinical DS risk score of >6 has significant practical implications for the resource-limited setting, presenting simple diagnostic criteria which can facilitate early correct treatment, specialist consultation and genetic testing.

Original languageEnglish (US)
Pages (from-to)99-105
Number of pages7
JournalSeizure
Volume62
DOIs
StatePublished - Nov 2018

Keywords

  • Epilepsy
  • Epileptic encephalopathy
  • Fbrile seizures
  • Genetic epilepsy
  • SCN1A
  • Sub-Saharan Africa

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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