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Published February 19, 2019 | Version v1
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Data from: Clinical spectrum of STX1B-related epileptic disorders

Creators

  • 1. University of Tübingen
  • 2. University of Luxembourg
  • 3. Meyer Children's Hospital
  • 4. University of Southern Denmark
  • 5. University College London
  • 6. Children's Hospital of Philadelphia
  • 7. Department of Pediatric Neurology, Centre de Compétences Maladies Rares, CHU Besançon*
  • 8. Lyon Neuroscience Research Center
  • 9. Mayo Clinic
  • 10. Neuropediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schoen Klinik Vogtareuth, Germany*
  • 11. Beaumont Hospital
  • 12. University of California, San Francisco
  • 13. Department of Neurology, University Hospitals Leuven, Belgium*
  • 14. Hvidovre Hospital
  • 15. Evelina London Children's Healthcare
  • 16. Children's Hospital Colorado
  • 17. Clinique Bernoise Montana, Crans-Montana, Switzerland*
  • 18. Kiel University
  • 19. Wellcome Centre for Human Genetics
  • 20. University of Milan
  • 21. University of Verona
  • 22. Ambry Genetics (United States)
  • 23. King's College London
  • 24. UCB Pharma (United Kingdom)
  • 25. University of Antwerp
  • 26. Newcastle University
  • 27. Swansea University
  • 28. Massachusetts General Hospital

Description

Objective: The aim of this study was to expand the spectrum of epilepsy syndromes related to STX1B, encoding the presynaptic protein syntaxin-1B, and establish genotype-phenotype correlations by identifying further disease-related variants. Methods: We used next generation sequencing in the framework of research projects and diagnostic testing. Clinical data and EEGs were reviewed, including already published cases. To estimate the pathogenicity of the variants, we used established and newly developed in silico prediction tools. Results: We describe 15 new variants in STX1B which are distributed across the whole gene. We discerned four different phenotypic groups across the newly identified and previously published patients (49 patients in 23 families): 1) Six sporadic patients or families (31 affected individuals) with febrile and afebrile seizures with a benign course, generally good drug response, normal development and without permanent neurological deficits; 2) two patients with genetic generalized epilepsy without febrile seizures and cognitive deficits; 3) 13 patients or families with intractable seizures, developmental regression after seizure onset and additional neuropsychiatric symptoms; 4) two patients with focal epilepsy. More often we found loss-of-function mutations in benign syndromes, whereas missense variants in the SNARE motif of syntaxin-1B were associated with more severe phenotypes. Conclusion: These data expand the genetic and phenotypic spectrum of STX1B-related epilepsies to a diverse range of epilepsies that span the ILAE classification. Variants in STX1B are protean and contribute to many different epilepsy phenotypes, similar to SCN1A, the most important gene associated with fever-associated epilepsies.

Notes

Supplements_STX1B_Wolking
Supplement_Figures

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Additional details

Related works

Is cited by
10.1212/wnl.0000000000007089 (DOI)