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Epilepsy and mental retardation restricted to females: X-linked epileptic infantile encephalopathy of unusual inheritance

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Abstract

Epilepsy in females with mental retardation (EFMR) is a rare early infantile epileptic encephalopathy (EIEE), phenotypically resembling Dravet syndrome (DS). It is characterised by a variable degree of intellectual deficits and epilepsy. EFMR is caused by heterozygous mutations in the PCDH19 gene (locus Xq22.1) encoding protocadherin-19, a protein that is highly expressed during brain development. The protein is involved in cell adhesion and probably plays an important role in neuronal migration and formation of synaptic connections. EFMR is considered X-linked of variable mutations’ penetrance. Mutations in the PCDH19 gene mainly arise de novo, but if inherited, they show a unique pattern of transmission. Females with heterozygous mutations are affected, while hemizygous males are not, regardless of mutation carriage. This singular mode might be explained by cell interference as a pathogenic molecular mechanism leading to neuronal dysfunction. Recently, PCDH19-related EIEE turned out to be more frequent than initially thought, contributing to around 16 % of cases (25 % in female groups) in the SCN1A-negative DS-like patients. Therefore, the PCDH19 gene is now estimated to be the second, after SCN1A, most clinically relevant gene in epilepsy.

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Acknowledgements

This work was supported by a grant from the MSHE/NSC international research project 800/N-ESF-EuroEPINOMICS/10/2011/0.

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Authors and Affiliations

  1. Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17A, 01-211, Warsaw, Poland

    Kinga Duszyc & Dorota Hoffman-Zacharska

  2. Clinic of Neurology for Children and Adolescents, Institute of Mother and Child, Kasprzaka 17A, 01-211, Warsaw, Poland

    Iwona Terczynska

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  1. Kinga Duszyc
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  2. Iwona Terczynska
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  3. Dorota Hoffman-Zacharska
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Correspondence to Dorota Hoffman-Zacharska.

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Duszyc, K., Terczynska, I. & Hoffman-Zacharska, D. Epilepsy and mental retardation restricted to females: X-linked epileptic infantile encephalopathy of unusual inheritance. J Appl Genetics 56, 49–56 (2015). https://doi.org/10.1007/s13353-014-0243-8

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  • DOI: https://doi.org/10.1007/s13353-014-0243-8

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