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Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders

(2013) NEUROGENETICS. 14(1). p.23-34
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Abstract
Epilepsy and mental retardation limited to females (EFMR), caused by PCDH19 mutations, has a variable clinical expression that needs further exploration. Onset of epilepsy may be provoked by fever and can resemble Dravet syndrome. Furthermore, transmitting males have no seizures, but are reported to have rigid personalities suggesting possible autism spectrum disorders (ASD). Therefore, this study aimed to determine the phenotypic spectrum associated with PCDH19 mutations in Dravet-like and EFMR female patients and in males with ASD. We screened 120 females suffering from Dravet-like epilepsy, 136 females with EFMR features and 20 males with ASD. Phenotypes and genotypes of the PCDH19 mutation carriers were compared with those of 125 females with EFMR reported in the literature. We report 15 additional patients with a PCDH19 mutation. Review of clinical data of all reported patients showed that the clinical picture of EFMR is heterogeneous, but epilepsy onset in infancy, fever sensitivity and occurrence of seizures in clusters are key features. Seizures remit in the majority of patients during teenage years. Intellectual disability and behavioural disturbances are common. Fifty percent of all mutations are missense mutations, located in the extracellular domains only. Truncating mutations have been identified in all protein domains. One ASD proband carried one missense mutation predicted to have a deleterious effect, suggesting that ASD in males can be associated with PCDH19 mutations.
Keywords
Epilepsy, PCDH19, X-linked, Genetics, FEMALES, Autism spectrum disorder, SEVERE MYOCLONIC EPILEPSY, PROTOCADHERIN 19 MUTATIONS, DRAVET-SYNDROME, MENTAL-RETARDATION, DE-NOVO, CONVULSIVE DISORDER, SCN1A MUTATIONS, FAMILIAL FORM, ONSET EPILEPSY

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MLA
van Harssel, JJT, et al. “Clinical and Genetic Aspects of PCDH19-Related Epilepsy Syndromes and the Possible Role of PCDH19 Mutations in Males with Autism Spectrum Disorders.” NEUROGENETICS, vol. 14, no. 1, 2013, pp. 23–34, doi:10.1007/s10048-013-0353-1.
APA
van Harssel, J., Weckhuysen, S., van Kempen, M., Hardies, K., Verbeek, N., de Kovel, C., … Brilstra, E. (2013). Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders. NEUROGENETICS, 14(1), 23–34. https://doi.org/10.1007/s10048-013-0353-1
Chicago author-date
Harssel, JJT van, S Weckhuysen, MJA van Kempen, K Hardies, NE Verbeek, CGF de Kovel, WB Gunning, et al. 2013. “Clinical and Genetic Aspects of PCDH19-Related Epilepsy Syndromes and the Possible Role of PCDH19 Mutations in Males with Autism Spectrum Disorders.” NEUROGENETICS 14 (1): 23–34. https://doi.org/10.1007/s10048-013-0353-1.
Chicago author-date (all authors)
van Harssel, JJT, S Weckhuysen, MJA van Kempen, K Hardies, NE Verbeek, CGF de Kovel, WB Gunning, E van Daalen, MV de Jonge, AC Jansen, RJ Vermeulen, WFM Arts, Helene Verhelst, A Fogarasi, JF de Rijk-van Andel, A Kelemen, D Lindhout, P De Jonghe, BPC Koeleman, A Suls, and EH Brilstra. 2013. “Clinical and Genetic Aspects of PCDH19-Related Epilepsy Syndromes and the Possible Role of PCDH19 Mutations in Males with Autism Spectrum Disorders.” NEUROGENETICS 14 (1): 23–34. doi:10.1007/s10048-013-0353-1.
Vancouver
1.
van Harssel J, Weckhuysen S, van Kempen M, Hardies K, Verbeek N, de Kovel C, et al. Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders. NEUROGENETICS. 2013;14(1):23–34.
IEEE
[1]
J. van Harssel et al., “Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders,” NEUROGENETICS, vol. 14, no. 1, pp. 23–34, 2013.
@article{3260579,
  abstract     = {{Epilepsy and mental retardation limited to females (EFMR), caused by PCDH19 mutations, has a variable clinical expression that needs further exploration. Onset of epilepsy may be provoked by fever and can resemble Dravet syndrome. Furthermore, transmitting males have no seizures, but are reported to have rigid personalities suggesting possible autism spectrum disorders (ASD). Therefore, this study aimed to determine the phenotypic spectrum associated with PCDH19 mutations in Dravet-like and EFMR female patients and in males with ASD. We screened 120 females suffering from Dravet-like epilepsy, 136 females with EFMR features and 20 males with ASD. Phenotypes and genotypes of the PCDH19 mutation carriers were compared with those of 125 females with EFMR reported in the literature. We report 15 additional patients with a PCDH19 mutation. Review of clinical data of all reported patients showed that the clinical picture of EFMR is heterogeneous, but epilepsy onset in infancy, fever sensitivity and occurrence of seizures in clusters are key features. Seizures remit in the majority of patients during teenage years. Intellectual disability and behavioural disturbances are common. Fifty percent of all mutations are missense mutations, located in the extracellular domains only. Truncating mutations have been identified in all protein domains. One ASD proband carried one missense mutation predicted to have a deleterious effect, suggesting that ASD in males can be associated with PCDH19 mutations.}},
  author       = {{van Harssel, JJT and Weckhuysen, S and van Kempen, MJA and Hardies, K and Verbeek, NE and de Kovel, CGF and Gunning, WB and van Daalen, E and de Jonge, MV and Jansen, AC and Vermeulen, RJ and Arts, WFM and Verhelst, Helene and Fogarasi, A and de Rijk-van Andel, JF and Kelemen, A and Lindhout, D and De Jonghe, P and Koeleman, BPC and Suls, A and Brilstra, EH}},
  issn         = {{1364-6745}},
  journal      = {{NEUROGENETICS}},
  keywords     = {{Epilepsy,PCDH19,X-linked,Genetics,FEMALES,Autism spectrum disorder,SEVERE MYOCLONIC EPILEPSY,PROTOCADHERIN 19 MUTATIONS,DRAVET-SYNDROME,MENTAL-RETARDATION,DE-NOVO,CONVULSIVE DISORDER,SCN1A MUTATIONS,FAMILIAL FORM,ONSET EPILEPSY}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{23--34}},
  title        = {{Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders}},
  url          = {{http://doi.org/10.1007/s10048-013-0353-1}},
  volume       = {{14}},
  year         = {{2013}},
}

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