Is focal cortical dysplasia sporadic? Family evidence for genetic susceptibility

Authors

  • Richard J. Leventer,

    Corresponding author
    1. Department of Neurology, Royal Children's Hospital, Melbourne, Victoria, Australia
    2. Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
    3. Department of Pediatrics, University of Melbourne, Melbourne, Victoria, Australia
    • Address correspondence to Richard J. Leventer, Department of Neurology, Royal Children's Hospital, Flemington Road, Parkville, Vic. 3052, Australia. E-mail: richard.leventer@rch.org.au

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    • These authors contributed equally to this work.
  • Floor E. Jansen,

    1. Department of Pediatric Neurology, Rudolf Magnus Institute of Neurosciences, University Medical Center Utrecht, Utrecht, The Netherlands
    2. Epilepsy Research Centre, University of Melbourne, Austin Health, Melbourne, Victoria, Australia
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    • These authors contributed equally to this work.
  • Simone A. Mandelstam,

    1. The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia
    2. Department of Radiology, University of Melbourne, Melbourne, Victoria, Australia
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  • Alice Ho,

    1. Departments of Pediatrics and Clinical Neurosciences, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada
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  • Ismail Mohamed,

    1. Department of Pediatrics, IWK Health Center, Dalhousie University, Halifax, Nova Scotia, Canada
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  • Harvey B. Sarnat,

    1. Department of Pediatrics, Pathology, (Neuropathology) and Clinical Neurosciences, University of Calgary Faculty of Medicine, Alberta Children's Hospital, Calgary, Alberta, Canada
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  • Mitsuhiro Kato,

    1. Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan
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  • Tatsuya Fukasawa,

    1. Department of Pediatrics, Anjo Kosei Hospital, Aichi, Japan
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  • Hirotomo Saitsu,

    1. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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  • Naomichi Matsumoto,

    1. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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  • Masayuki Itoh,

    1. Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
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  • Renate M. Kalnins,

    1. Department of Anatomical Pathology, Austin Hospital, Melbourne, Victoria, Australia
    2. Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia
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  • Chung W. Chow,

    1. Department of Pediatrics, University of Melbourne, Melbourne, Victoria, Australia
    2. Department of Anatomical Pathology, Royal Children's Hospital, Melbourne, Victoria, Australia
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  • A. Simon Harvey,

    1. Department of Neurology, Royal Children's Hospital, Melbourne, Victoria, Australia
    2. Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
    3. Department of Pediatrics, University of Melbourne, Melbourne, Victoria, Australia
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  • Graeme D. Jackson,

    1. Epilepsy Research Centre, University of Melbourne, Austin Health, Melbourne, Victoria, Australia
    2. Department of Radiology, University of Melbourne, Melbourne, Victoria, Australia
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  • Peter B. Crino,

    1. Shriners Hospitals Pediatric Research Center, Temple University, Philadelphia, Pennsylvania, U.S.A
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  • Samuel F. Berkovic,

    1. Epilepsy Research Centre, University of Melbourne, Austin Health, Melbourne, Victoria, Australia
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  • Ingrid E. Scheffer

    1. Department of Neurology, Royal Children's Hospital, Melbourne, Victoria, Australia
    2. Department of Pediatrics, University of Melbourne, Melbourne, Victoria, Australia
    3. Epilepsy Research Centre, University of Melbourne, Austin Health, Melbourne, Victoria, Australia
    4. Department of Radiology, University of Melbourne, Melbourne, Victoria, Australia
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Summary

Focal cortical dysplasia is a common cortical malformation and an important cause of epilepsy. There is evidence for shared molecular mechanisms underlying cortical dysplasia, ganglioglioma, hemimegalencephaly, and dysembryoplastic neuroepithelial tumor. However, there are no familial reports of typical cortical dysplasia or co-occurrence of cortical dysplasia and related lesions within the same pedigree. We report the clinical, imaging, and histologic features of six pedigrees with familial cortical dysplasia and related lesions. Twelve patients from six pedigrees were ascertained from pediatric and adult epilepsy centers, eleven of whom underwent epilepsy surgery. Pedigree data, clinical information, neuroimaging findings, and histopathologic features are presented. The families comprise brothers with focal cortical dysplasia, a male and his sister with focal cortical dysplasia, a female with focal cortical dysplasia and her brother with hemimegalencephaly, a female with focal cortical dysplasia and her female first cousin with ganglioglioma, a female with focal cortical dysplasia and her male cousin with dysembryoplastic neuroepithelial tumor, and a female and her nephew with focal cortical dysplasia. This series shows that focal cortical dysplasia can be familial and provides clinical evidence suggesting that cortical dysplasia, hemimegalencephaly, ganglioglioma, and dysembryoplastic neuroepithelial tumors may share common genetic determinants.

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