Hostname: page-component-55f67697df-zh294 Total loading time: 0 Render date: 2025-05-11T04:00:16.692Z Has data issue: false hasContentIssue false
  • English
  • Français

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]
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
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

References

1.Goodship, J, Cross, I, LiLing, J, Wren, C.A population study of chromosome 22q11 deletions in infancy. Arch Dis Child. 1998;79:348–51.Google Scholar
2.Scambler, PJ.The 22q11 deletion syndromes. Hum Mol Genet. 2000;9:2421–6.Google Scholar
3.Driscoll, DA.Molecular and genetic aspects of DiGeorge/velocardiofacial syndrome. Methods Mol Med. 2006;126:43–55.Google Scholar
4.Bassett, AS, Marshall, CR, Lionel, AC, Chow, EW, Scherer, SW.Copy number variations and risk for schizophrenia in 22q11.2 deletion syndrome. Hum Mol Genet. 2008;17:4045–53.Google Scholar
5.Weksberg, R, Stachon, AC, Squire, JA, et al.Molecular characterization of deletion breakpoints in adults with 22q11 deletion syndrome. Hum Genet. 2007;120:837–45.Google Scholar
6.Bassett, AS, Chow, EW, Husted, J, et al.Clinical features of 78 adults with 22q11 Deletion Syndrome. Am J Med Genet. 2005;138:307–13.Google Scholar
7.Shprintzen, RJ, Goldberg, RB, Lewin, ML, et al.A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome. Cleft Palate J. 1978;15:56–62.Google ScholarPubMed
8.Matsuoka, R, Kimura, M, Scambler, PJ, et al.Molecular and clinical study of 183 patients with conotruncal anomaly face syndrome. Hum Genet. 1998;103:70–80.CrossRefGoogle ScholarPubMed
9.Murphy, KC, Jones, LA, Owen, MJ.High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry. 1999;56:940–5.CrossRefGoogle ScholarPubMed
10.Cohen, E, Chow, EW, Weksberg, R, Bassett, AS.Phenotype of adults with the 22q11 deletion syndrome: a review. Am J Med Genet. 1999;86:359–65.3.0.CO;2-V>CrossRefGoogle ScholarPubMed
11.Kao, A, Mariani, J, McDonald-McGinn, DM, et al.Increased prevalence of unprovoked seizures in patients with a 22q11.2 deletion. Am J Med Genet. 2004;129A:29–34.Google Scholar
12.Ryan, AK, Goodship, JA, Wilson, DI, et al.Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet. 1997;34:798–804.CrossRefGoogle ScholarPubMed
13.Robin, NH, Taylor, CJ, McDonald-McGinn, DM, et al.Polymicrogyria and deletion 22q11.2 syndrome: window to the etiology of a common cortical malformation. Am J Med Genet. 2006;140:2416–25.Google Scholar
14.Kiehl, TR, Chow, EW, Mikulis, DJ, George, SR, Bassett, AS.Neuropathologic features in adults with 22q11.2 deletion syndrome. Cereb Cortex. 2009;19:153–64.Google Scholar
15.Debbane, M, Schaer, M, Farhoumand, R, Glaser, B, Eliez, S.Hippocampal volume reduction in 22q11.2 deletion syndrome. Neuropsychologia. 2006;44:2360–5.Google Scholar
16.Driscoll, DA, Salvin, J, Sellinger, B, et al.Prevalence of 22q11 microdeletions in DiGeorge and velocardiofacial syndromes: implications for genetic counselling and prenatal diagnosis. J Med Genet. 1993;30:813–17.CrossRefGoogle ScholarPubMed
17.Barsi, P, Kenez, J, Solymosi, D, et al.Hippocampal malrotation with normal corpus callosum: a new entity? Neuroradiology. 2000;42:339–45.Google Scholar
18.Gamss, RP, Slasky, SE, Bello, JA, Miller, TS, Shinnar, S.Prevalence of hippocampal malrotation in a population without seizures. AJNR Am J Neuroradiol. 2009;30:1571–3.Google Scholar
19.Bajic, D, Wang, C, Kumlien, E, et al.Incomplete inversion of the hippocampus-a common developmental anomaly.. Eur Radiol. 2008;18:138–42.Google Scholar
20.Bernasconi, N, Kinay, D, Andermann, F, Antel, S, Bernasconi, A.Analysis of shape and positioning of the hippocampal formation: an MRI study in patients with partial epilepsy and healthy controls. Brain. 2005;128:2442–52.Google Scholar
21.Lewis, CS, Bello, JA.HIMAL is a malformation that predisposes to prolonged febrile seizures: data from FEBSTAT study. Epilepsia. 2006;47 16.Google Scholar
22.Eliez, S, Schmitt, JE, White, CD, Reiss, AL.Children and adolescents with velocardiofacial syndrome: a volumetric MRI study. Am J Psychiatry. 2000;157:409–15.Google Scholar
23.Eliez, S, Blasey, CM, Schmitt, EJ, White, CD, Hu, D, Reiss, AL.Velocardiofacial syndrome: are structural changes in the temporal and mesial temporal regions related to schizophrenia? Am J Psychiatry. 2001;158:447–53.Google Scholar
24.Deboer, T, Wu, Z, Lee, A, Simon, TJ.Hippocampal volume reduction in children with chromosome 22q11.2 deletion syndrome is associated with cognitive impairment. Behav Brain Funct. 2007;3:54.Google Scholar
25.Eliez, S, Schmitt, JE, White, CD, Wellis, VG, Reiss, AL.A quantitative MRI study of posterior fossa development in velocardiofacial syndrome. Biol Psychiatry. 2001;49:540–6.CrossRefGoogle ScholarPubMed
26.Bish, JP, Nguyen, V, Ding, L, Ferrante, S, Simon, TJ.Thalamic reductions in children with chromosome 22q11.2 deletion syndrome. Neuroreport. 2004;15:1413–15.Google Scholar
27.Eliez, S, Barnea-Goraly, N, Schmitt, JE, Liu, Y, Reiss, AL.Increased basal ganglia volumes in velo-cardio-facial syndrome (deletion 22q11.2). Biol Psychiatry. 2002;52:68–70.CrossRefGoogle ScholarPubMed
28.Kates, WR, Burnette, CP, Bessette, BA, et al.Frontal and caudate alterations in velocardiofacial syndrome (deletion at chromosome 22q11.2). J Child Neurol. 2004;19:337–42.Google Scholar
29.Baulac, M, De Grissac, N, Hasboun, D, et al.Hippocampal developmental changes in patients with partial epilepsy: magnetic resonance imaging and clinical aspects. Ann Neurol. 1998;44:223–33.Google Scholar
30.Matsufuji, M, Utsunomiya, H, Inoue, T, Yasumoto, S, Takashima, S, Mitsudome, A.Magnetic resonance imaging volumetry and clinical analysis of epilepsy patients with unilateral hippocampal abnormality. Pediatr Int. 2012;54:19–26.Google Scholar
31.Bajic, D, Ewald, U, Raininko, R.Hippocampal development at gestation weeks 23 to 36. An ultrasound study on preterm neonates. Neuroradiology. 2010;52:489–94.Google Scholar
32.Montenegro, MA, Kinay, D, Cendes, F, et al.Patterns of hippocampal abnormalities in malformations of cortical development. J Neurol Neurosurg Psychiatry. 2006;77:367–71.CrossRefGoogle ScholarPubMed
33.Maynard, TM, Gopalakrishna, D, Meechan, D, Paronett, E, Newbern, J, Lamantia, AS.22q11 gene dosage establishes an adaptive range for sonic hedgehog and retinoic acid signaling during early development. Hum Mol Genet. 2013;22:300–12.Google Scholar
34.Stiers, P, Fonteyne, A, Wouters, H, D'Agostino, E, Sunaert, S, Lagae, L.Hippocampal malrotation in pediatric patients with epilepsy associated with complex prefrontal dysfunction. Epilepsia. 2010;51:546–55.Google Scholar
35.Connor, SE, Ng, V, McDonald, C, et al.A study of hippocampal shape anomaly in schizophrenia and in families multiply affected by schizophrenia or bipolar disorder. Neuroradiology. 2004;46:523–34.Google Scholar