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Hippocampal Malrotation is Associated with Chromosome 22q11.2 Microdeletion

Published online by Cambridge University Press:  23 September 2014

Danielle M. Andrade ,
Timo Krings ,
Eva W. C. Chow ,
Tim-Rasmus Kiehl  and
Anne S. Bassett
Danielle M. Andrade*
Affiliation:
Division of Neurology, University of Toronto
Timo Krings
Affiliation:
Department of Radiology, University of Toronto
Eva W. C. Chow
Affiliation:
Krembil Neuroscience Program, Department of Psychiatry, University of Toronto Clinical Genetics Research Program, Centre for Addiction and Mental Health
Tim-Rasmus Kiehl
Affiliation:
Department of Laboratory Medicine and Pathobiology, Toronto Western Hospital, University of Toronto Department of Pathology, University Health Network, Toronto, Ontario, Canada
Anne S. Bassett
Affiliation:
Krembil Neuroscience Program, Department of Psychiatry, University of Toronto Clinical Genetics Research Program, Centre for Addiction and Mental Health Division of Cardiology, Department of Medicine, University Health Network, Toronto, Ontario, Canada
*
5W-445, Toronto Western Hospital, University of Toronto, Toronto, Ontario, M5T 2S8, Canada. Email: [email protected]
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Abstract:

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Background:

Patients with chromosome 22q11.2 deletion syndrome (22q11DS) are at a seven fold increased risk of developing seizures. However, only a fraction of these patients exhibit structural abnormalities such as polymicrogyria (PMG) and periventricular nodular heterotopia (PNH) that are known to cause seizures and to be associated with 22q11DS. In this study we used a dedicated seizure imaging protocol to look for additional structural abnormalities in these individuals that may explain the elevated risk of seizure disorder in this patient group.

Methods:

Nineteen consecutive adult subjects with 22q11DS underwent a 3 Tesla MRI with a dedicated high-resolution seizure protocol. Neurological exam was performed in all patients. Genome-wide analysis excluded the presence of other pathogenic microdeletions or duplications.

Results:

Structural abnormalities were found in 11 of 14 subjects with sufficient image quality. These included three patients with PNH, one of whom had associated PMG. In addition, there was a surprisingly high prevalence of unilateral hippocampal malrotation (HIMAL), observed in 9 of 14 cases (64%). EEG findings showed interictal epileptiform discharges with focal distribution in four patients and generalized discharges in one patient.

Conclusion:

The results suggest that, in addition to other known structural abnormalities, 22q11DS is associated with HIMAL. It has been suggested that this developmental abnormality of the hippocampus may predispose or otherwise contribute to epileptogenesis. However in this study we observed HIMAL in a large proportion of patients, with and without epilepsy. Therefore, other as yet unknown factors may contribute to the high prevalence of epilepsy in this population.

Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 40 , Issue 5 , September 2013 , pp. 652 - 656
Copyright
Copyright © The Canadian Journal of Neurological 2013

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