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Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations

(2010) NEUROLOGY. 75(13). p.1159-1165
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Abstract
Objectives: Heterozygous mutations in STXBP1, encoding the syntaxin binding protein 1, have recently been identified in Ohtahara syndrome, an epileptic encephalopathy with very early onset. In order to explore the phenotypic spectrum associated with STXBP1 mutations, we analyzed a cohort of patients with unexplained early-onset epileptic encephalopathies. Methods: We collected and clinically characterized 106 patients with early-onset epileptic encephalopathies. Mutation analysis of the STXBP1 gene was done using sequence analysis of the exon and intron-exon boundaries and multiplex amplification quantification to detect copy number variations. Results: We identified 4 truncating mutations and 2 microdeletions partially affecting STXBP1 in 6 of the 106 patients. All mutations are predicted to abolish STXBP1 function and 5 mutations were proven to occur de novo. None of the mutation-carrying patients had Ohtahara syndrome. One patient was diagnosed with West syndrome at disease onset, while the initial phenotype of 5 further patients did not fit into a specific recognized epilepsy syndrome. Three of these patients later evolved to West syndrome. All patients had severe to profound mental retardation, and ataxia or dyskinetic movements were present in 5 patients. Conclusion: This study shows that mutations in STXBP1 are not limited to patients with Ohtahara syndrome, but are also present in 10% (5/49) of patients with an early-onset epileptic encephalopathy that does not fit into either Ohtahara or West syndrome and rarely in typical West syndrome. STXBP1 mutational analysis should be considered in the diagnostic evaluation of this challenging group of patients.
Keywords
MUNC18-1

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MLA
Deprez, L., et al. “Clinical Spectrum of Early-Onset Epileptic Encephalopathies Associated with STXBP1 Mutations.” NEUROLOGY, vol. 75, no. 13, 2010, pp. 1159–65.
APA
Deprez, L., Weckhuysen, S., Holmgren, P., Suls, A., Van Dyck, T., Goossens, D., … De Jonghe, P. (2010). Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations. NEUROLOGY, 75(13), 1159–1165.
Chicago author-date
Deprez, L, S Weckhuysen, P Holmgren, A Suls, T Van Dyck, D Goossens, J Del-Favero, et al. 2010. “Clinical Spectrum of Early-Onset Epileptic Encephalopathies Associated with STXBP1 Mutations.” NEUROLOGY 75 (13): 1159–65.
Chicago author-date (all authors)
Deprez, L, S Weckhuysen, P Holmgren, A Suls, T Van Dyck, D Goossens, J Del-Favero, A Jansen, K Verhaert, L Lagae, A Jordanova, Rudy Van Coster, S Yendle, S Berkovic, I Scheffer, B Ceulemans, and P De Jonghe. 2010. “Clinical Spectrum of Early-Onset Epileptic Encephalopathies Associated with STXBP1 Mutations.” NEUROLOGY 75 (13): 1159–1165.
Vancouver
1.
Deprez L, Weckhuysen S, Holmgren P, Suls A, Van Dyck T, Goossens D, et al. Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations. NEUROLOGY. 2010;75(13):1159–65.
IEEE
[1]
L. Deprez et al., “Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations,” NEUROLOGY, vol. 75, no. 13, pp. 1159–1165, 2010.
@article{1061274,
  abstract     = {{Objectives: Heterozygous mutations in STXBP1, encoding the syntaxin binding protein 1, have recently been identified in Ohtahara syndrome, an epileptic encephalopathy with very early onset. In order to explore the phenotypic spectrum associated with STXBP1 mutations, we analyzed a cohort of patients with unexplained early-onset epileptic encephalopathies.
Methods: We collected and clinically characterized 106 patients with early-onset epileptic encephalopathies. Mutation analysis of the STXBP1 gene was done using sequence analysis of the exon and intron-exon boundaries and multiplex amplification quantification to detect copy number variations.
Results: We identified 4 truncating mutations and 2 microdeletions partially affecting STXBP1 in 6 of the 106 patients. All mutations are predicted to abolish STXBP1 function and 5 mutations were proven to occur de novo. None of the mutation-carrying patients had Ohtahara syndrome. One patient was diagnosed with West syndrome at disease onset, while the initial phenotype of 5 further patients did not fit into a specific recognized epilepsy syndrome. Three of these patients later evolved to West syndrome. All patients had severe to profound mental retardation, and ataxia or dyskinetic movements were present in 5 patients.
Conclusion: This study shows that mutations in STXBP1 are not limited to patients with Ohtahara syndrome, but are also present in 10% (5/49) of patients with an early-onset epileptic encephalopathy that does not fit into either Ohtahara or West syndrome and rarely in typical West syndrome. STXBP1 mutational analysis should be considered in the diagnostic evaluation of this challenging group of patients.}},
  author       = {{Deprez, L and Weckhuysen, S and Holmgren, P and Suls, A and Van Dyck, T and Goossens, D and Del-Favero, J and Jansen, A and Verhaert, K and Lagae, L and Jordanova, A and Van Coster, Rudy and Yendle, S and Berkovic, S and Scheffer, I and Ceulemans, B and De Jonghe, P}},
  issn         = {{0028-3878}},
  journal      = {{NEUROLOGY}},
  keywords     = {{MUNC18-1}},
  language     = {{eng}},
  number       = {{13}},
  pages        = {{1159--1165}},
  title        = {{Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations}},
  url          = {{http://www.neurology.org/cgi/content/abstract/75/13/1159}},
  volume       = {{75}},
  year         = {{2010}},
}

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