Evidence map›Paper›PMID 30321769›Full record

ArticleSeizure2018

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

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Seizure, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 2 pooled it
1.0field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 2 syntheses or guidelines pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. [Early identification and diagnosis of epilepsy related to fever sensitivity].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2021
    Article
  5. Review
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 6 institutions in 3 countries.

Alina I EsterhuizenDivision of Human Genetics, Institute of Infectious Diseases and Molecular Medicine, Department of Pathology, University of Cape Town, Cape Town, South Africa; National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa. Electronic address: alina.esterhuizen@uct.ac.za.
Heather C MeffordDepartment of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA, USA. Electronic address: hmefford@uw.edu.
Rajkumar S RamesarDivision of Human Genetics, Institute of Infectious Diseases and Molecular Medicine, Department of Pathology, University of Cape Town, Cape Town, South Africa; National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa. Electronic address: raj.ramesar@uct.ac.za.
Shuyu WangDepartment of General Medicine, Alfred Health, Victoria, Australia. Electronic address: sh.wang@alfred.org.au.
Gemma L CarvillKen and Ruth Davee Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. Electronic address: gemma.carvill@northwestern.edu.
Jo M WilmshurstPaediatric Neurology and Neurophysiology, Red Cross Children's War Memorial Hospital, Cape Town, South Africa; School of Child and Adolescent Health, University of Cape Town, South Africa. Electronic address: jo.wilmshurst@uct.ac.za.
Alfred Health · AUGroote Schuur Hospital · ZANational Health Laboratory Service · ZANorthwestern University · USUniversity of Cape Town · ZAUniversity of Washington · US

Funding

A Genomic Approach to EpilepsyR01NS069605 · NINDS · UNIVERSITY OF WASHINGTON · PI MEFFORD, HEATHER C. · 2010 to 2019
$4.9M
An epigenomic approach to identifying noncoding mutations in epilepsyR00NS089858 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CARVILL, GEMMA LOUISE · 2016 to 2018
$744k
An epigenomic approach to identifying noncoding mutations in epilepsyK99NS089858 · NINDS · UNIVERSITY OF WASHINGTON · PI CARVILL, GEMMA LOUISE · 2014 to 2015
$182k
NINDS NIH HHS K99 NS089858NINDS NIH HHS R00 NS089858NINDS NIH HHS R01 NS069605
6 · The paper itself

Abstract

purposeDravet 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.

methodWe 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.

resultsDisease-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.

conclusionThis 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.

Indexed as

Early DiagnosisCadherinsChild, PreschoolCohort StudiesElectroencephalographyEpilepsies, MyoclonicFemaleGenetic TestingHumansInfantMaleMutationNAV1.1 Voltage-Gated Sodium ChannelProtocadherinsSeverity of Illness IndexSouth AfricaCadherinsNAV1.1 Voltage-Gated Sodium ChannelPCDH19 protein, humanProtocadherinsSCN1A protein, humanEpilepsyEpileptic encephalopathyFbrile seizuresGenetic epilepsySCN1ASub-Saharan Africa

Identifiers

PMID30321769
PMCPMC6261486
OpenAlexW2890814914

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.