Kleefstra syndrome in three adult patients: Further delineation of the behavioral and neurological phenotype shows aspects of a neurodegenerative course

Authors

  • Willem M.A. Verhoeven,

    Corresponding author
    1. Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, The Netherlands
    2. Erasmus University Medical Centre, Department of Psychiatry, Rotterdam, The Netherlands
    • Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Stationsweg 46, 5803AC Venray, The Netherlands.

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  • Jos I.M. Egger,

    1. Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, The Netherlands
    2. Donders Centre for Cognition, Radboud University Nijmegen, Nijmegen, The Netherlands
    3. Behavioral Science Institute, Radboud University Nijmegen, Nijmegen, The Netherlands
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  • Karlijn Vermeulen,

    1. Karakter, Department of Child and Adolescent Psychiatry, Radboud University Nijmegen, Nijmegen, The Netherlands
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  • Bart P.C. van de Warrenburg,

    1. Department of Neurology, Donders Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • Tjitske Kleefstra

    1. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • How to Cite this Article: Verhoeven WMA, Egger JIM, Vermeulen K, van de Warrenburg BPC, Kleefstra T. 2011. Kleefstra syndrome in three adult patients: Further delineation of the behavioral and neurological phenotype shows aspects of a neurodegenerative course. Am J Med Genet Part A 155:2409–2415.

Abstract

Kleefstra syndrome (KS), previously known as the 9q subtelomeric deletion syndrome (9qSTDS) is caused by haploinsufficiency of the EHMT1 gene. Both a single mutation and 9q34 microdeletions encompassing the entire gene can be responsible for this syndrome which is characterized by intellectual disability, hypotonia, and typical dysmorphisms, and may be associated with congenital heart and/or renal defects and epilepsy. Its behavioral phenotype has recently been described and comprises particular sleep disturbances and apathy. In this report, the evolution of the behavioral profile of KS is outlined by the description of three female patients aged 19, 33, and 43 years, respectively. In two patients, the syndrome was caused by an intragenic mutation and in the third by a 9q34 microdeletion encompassing the EHMT1 gene. MRI scanning of the brain in the two eldest patients demonstrated multifocal subcortical signal abnormalities. In general, the severity of the behavioral and motor deficiencies increased over time and became apparent after adolescence. It is concluded that the “regressive” phenotype of KS seems to be associated with the EHMT1 gene in particular. In addition, the utility of uncritical use of a classificatory diagnostic approach is discussed in the context of the motor and motivational disturbances that are prominent in this syndrome. © 2011 Wiley-Liss, Inc.

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