title: Hippocampal malrotation is associated with chromosome 22q11.2 microdeletion.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Division of Neurology, University of Toronto.
authors: Danielle M
authors: DM
authors: Andrade
authors: Timo
authors: T
authors: Krings
authors: Eva W C
authors: EW
authors: Chow
authors: Tim-Rasmus
authors: TR
authors: Kiehl
authors: Anne S
authors: AS
authors: Bassett
mesh_terms: D000015:Abnormalities, Multiple / Q000473:pathology*; D000328:Adult; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D015331:Cohort Studies; D004062:DiGeorge Syndrome / Q000150:complications / Q000473:pathology*; D004569:Electroencephalography; D004827:Epilepsy / Q000175:diagnosis / Q000209:etiology; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D012189:Retrospective Studies; D055815:Young Adult
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