Neuropathologic Features in Adults with 22q11.2 Deletion Syndrome
Abstract
The 22q11.2 deletion syndrome (22qDS) is the most common microdeletion syndrome in humans. Its multisystem manifestations include congenital anomalies and neuropsychiatric disorders such as schizophrenia. Structural neuroimaging shows various abnormalities, but no postmortem brain studies exist. We report neuropathologic findings in 3 individuals from a cohort of 100 adults with a confirmed 22q11.2 deletion. All 3 had schizophrenia. Postmortem examination of Case 1, a 44-year-old male, revealed bilateral periventricular nodular heterotopia in the frontal lobes and ectopic neurons scattered throughout the frontal white matter. Cases 2 (male, aged 22 years) and 3 (female, 52 years) showed no evidence of migration abnormalities, but both had extensive astrocytic gliosis and focal collections of macrophages in the cerebral white matter, suggestive of cerebrovascular pathology. Review of magnetic resonance imaging findings available for 66 other subjects in the cohort revealed polymicrogyria in one and right cerebellar disorganization in another of the 26 subjects with schizophrenia. The results support previous neuroimaging reports suggesting that neuronal migration abnormalities may be a feature of 22qDS. Both early developmental brain abnormalities and fetal and later microvascular pathology may play a role in the pathogenesis of the neuropsychiatric phenotype of 22qDS, including white matter abnormalities and schizophrenia.
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Imaging studies in 22q11.2 syndrome have revealed smaller brain volume, decreased cortical thickness in the superior parietal, right parietooccipital and inferior frontal gyrus, heterotopias and fewer gyri, and reduced volume in the hippocampus, cerebellum and amygdala, some of which varies based on the presence of schizophrenia or cognitive deficits.
“Imaging studies in 22q11.2 syndrome have revealed smaller brain volume [361], decreased cortical thickness in the superior parietal, right parietooccipital and inferior frontal gyrus, heterotopias and fewer gyri [27, 193, 314], and reduced volume in the hippocampus [84, 85], cerebellum [49] and amygdala [85], some of which varies based on the presence of schizophrenia or cognitive deficits [20, 31”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [193]
Cites
McDonald-McGinn, D. M., Sullivan, K. E., Marino, B., Philip, N., Swillen, A., Vorstman, J. A. S., Zackai, E. H., Emanuel, B. S., Vermeesch, J. R., Morrow, B. E., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.71 · Cited by 2,236 · see citing works
Self-citationThe neuropathology of schizophrenia
Harrison, P. J. (1999) · Brain · doi:10.1093/brain/122.4.593 · Cited by 1,677 · see citing works
Harrison, P. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1761-y · Cited by 693 · see citing works
Driscoll, D. A., Salvin, J., Sellinger, B., Budarf, M. L., McDonald‐McGinn, D. M., Zackai, E. H., & Emanuel, B. S. (1993) · Journal of Medical Genetics · doi:10.1136/jmg.30.10.813 · Cited by 487 · see citing works
Clinical features of 78 adults with 22q11 deletion syndrome
Bassett, A. S., Chow, E. W. C., Husted, J., Weksberg, R., Caluseriu, O., Webb, G. D., & Gatzoulis, M. Α. (2005) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30984 · Cited by 476 · see citing works
Self-citationCongenital heart disease in mice deficient for the DiGeorge syndrome region
Lindsay, E. A., Botta, A., Jurecic, V., Carattini-Rivera, S., Cheah, Y.-C., Rosenblatt, H. M., Bradley, A., & Baldini, A. (1999) · Nature · doi:10.1038/43900 · Cited by 426 · see citing works
Incidence and prevalence of the 22q11 deletion syndrome: a population-based study in Western Sweden
Óskarsdóttir, S. (2004) · Archives of Disease in Childhood · doi:10.1136/adc.2003.026880 · Cited by 401 · see citing works
Paylor, R. E., Pourcain, B. S., Mupo, A., Ataliotis, P., Spencer, C. M., Sobotka, A., Sparks, C., Choi, C.-H., Oghalai, J. S., Curran, S. R., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600206103 · Cited by 381 · see citing works
The Schizophrenia Phenotype in 22q11 Deletion Syndrome
Bassett, A. S., Chow, E. W. C., AbdelMalik, P., Gheorghiu, M., Husted, J., & Weksberg, R. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.9.1580 · Cited by 338 · see citing works
Self-citation22q11 deletion syndrome: a genetic subtype of schizophrenia
Bassett, A. S., & Chow, E. W. C. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00114-6 · Cited by 318 · see citing works
Self-citationVEGF: A modifier of the del22q11 (DiGeorge) syndrome?
Stalmans, I., Lambrechts, D., Smet, F. D., et al. (2003) · Nature Medicine · doi:10.1038/nm819 · Cited by 311 · see citing works
Guris, D. L., Fantes, J. A., Tara, D., Druker, B. J., & Imamoto, A. (2001) · Nature Genetics · doi:10.1038/85855 · Cited by 306 · see citing works
Schizophrenia and the brain: a prospective clinico-neuropathological study
Bruton, C. J., Crow, T. J., Frith, C., Johnstone, E. C., Owens, D. G. C., & Roberts, G. W. (1990) · Psychological Medicine · doi:10.1017/s0033291700017608 · Cited by 285 · see citing works
Drug-induced stimulation and suppression of action monitoring in healthy volunteers
de Bruijn, E. R. A., Hulstijn, W., Verkes, R. J., Ruigt, G. S. F., & Sabbe, B. G. C. (2004) · Psychopharmacology · doi:10.1007/s00213-004-1915-6 · Cited by 282 · see citing works
A genetic link betweenTbx1and fibroblast growth factor signaling
Vitelli, F., Taddei, I., Morishima, M., et al. (2002) · Development · doi:10.1242/dev.129.19.4605 · Cited by 282 · see citing works
Zweier, C., Sticht, H., Aydin-Yaylagül, I., Campbell, C. E., & Rauch, A. M. (2007) · The American Journal of Human Genetics · doi:10.1086/511993 · Cited by 217 · see citing works
Guris, D. L., Duester, G., Papaioannou, V. E., & Imamoto, A. (2006) · Developmental Cell · doi:10.1016/j.devcel.2005.12.002 · Cited by 212 · see citing works
Neurocognitive profile in 22q11 deletion syndrome and schizophrenia
Chow, E. W. C., Watson, M., Young, D. A., & Bassett, A. S. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2006.04.007 · Cited by 186 · see citing works
Self-citationCampbell, L., Daly, E., Toal, F., Stevens, A., Azuma, R., Catani, M., Ng, V., van Amelsvoort, T., Chitnis, X., Cutter, W., et al. (2006) · Brain : a journal of neurology · doi:10.1093/brain/awl066 · Cited by 184 · see citing works
Simon, T. J., Ding, L., Bish, J. P., McDonald‐McGinn, D. M., Zackai, E. H., & Gee, J. C. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2004.11.018 · Cited by 181 · see citing works
Genetic malformations of cortical development
Guerrini, R., & Marini, C. (2006) · Experimental Brain Research · doi:10.1007/s00221-006-0501-z · Cited by 157 · see citing works
A comprehensive analysis of 22q11 gene expression in the developing and adult brain
Maynard, T. M., Haskell, G., Peters, A. Z., Sikich, L., Lieberman, J. A., & LaMantia, A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2235651100 · Cited by 154 · see citing works
Crkl deficiency disrupts Fgf8 signaling in a mouse model of 22q11 deletion syndromes.
Moon, A., Guris, D. L., Seo, J.-H., Li, L., Hammond, J. W., Talbot, A., & Imamoto, A. (2006) · Developmental Cell · doi:10.1016/j.devcel.2005.12.003 · Cited by 150 · see citing works
Robin, N. H., Taylor, C. J., McDonald‐McGinn, D. M., Zackai, E. H., Bingham, P. M., Collins, K. J., Earl, D., Gill, D. S., Granata, T., Guerrini, R., et al. (2006) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31443 · Cited by 145 · see citing works
Aberrant interchromosomal exchanges are the predominant cause of the 22q11.2 deletion
Saitta, S. C., Harris, S. E., Gaeth, A. P., Driscoll, D. A., McDonald‐McGinn, D. M., Maisenbacher, M. K., Yersak, J. M., Chakraborty, P. K., Hacker, A. M., Zackai, E. H., et al. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddh041 · Cited by 145 · see citing works
van Amelsvoort, T., Daly, E., Henry, J., Robertson, D., Ng, V., Owen, M., Murphy, K. C., & Murphy, D. G. M. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.11.1085 · Cited by 139 · see citing works
Qualitative MRI findings in adults with 22q11 deletion syndrome and schizophrenia
Chow, E. W. C., Mikulis, D. J., Zipursky, R. B., et al. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00150-x · Cited by 123 · see citing works
Self-citationLaMantia, A. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00002-5 · Cited by 106 · see citing works
Structural brain abnormalities in patients with schizophrenia and 22q11 deletion syndrome
Chow, E. W. C., Zipursky, R. B., Mikulis, D. J., & Bassett, A. S. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01246-x · Cited by 105 · see citing works
Self-citationFrontal and Caudate Alterations in Velocardiofacial Syndrome (Deletion at Chromosome 22q11.2)
Kates, W. R., Burnette, C. P., Bessette, B. A., Folley, B. S., Strunge, L., Jabs, E. W., & Pearlson, G. D. (2004) · Journal of Child Neurology · doi:10.1177/088307380401900506 · Cited by 97 · see citing works
Amygdalo‐Entorhinal Inputs to the Hippocampal Formation in Relation to Schizophrenia
Benes, F. M., & Berretta, S. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06733.x · Cited by 80 · see citing works
Long, J. M., LaPorte, P., Merscher, S., Funke, B., Saint-Jore, B., Puech, A., Kucherlapati, R., Morrow, B. E., Skoultchi, A. I., & Wynshaw-Boris, A. J. (2006) · Neurogenetics · doi:10.1007/s10048-006-0054-0 · Cited by 79 · see citing works
Schaer, M., Eric Schmitt, J., Glaser, B., Lazeyras, F., Delavelle, J., & Eliez, S. (2006) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2005.10.002 · Cited by 76 · cited 4× · see citing works
“Keywords: neuronal migration, pathology, schizophrenia, velocardiofacial syndrome”
BackgroundResultInfluentialA survey of the 22q11 microdeletion in a large cohort of schizophrenia patients
Horowitz, A., Shifman, S., Rivlin, N., Pisanté, A., & Darvasi, A. (2004) · Schizophrenia Research · doi:10.1016/j.schres.2004.02.008 · Cited by 67 · see citing works
Specific cerebellar reductions in children with chromosome 22q11.2 deletion syndrome
Bish, J. P., Pendyal, A., Ding, L., Ferrante, H., Nguyen, V., McDonald‐McGinn, D. M., Zackai, E. H., & Simon, T. J. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.02.001 · Cited by 60 · see citing works
Molecular characterization of deletion breakpoints in adults with 22q11 deletion syndrome
Weksberg, R., Stachon, A. C., Squire, J. A., Moldovan, L., Bayani, J., Meyn, M. S., Chow, E. W. C., & Bassett, A. S. (2006) · Human Genetics · doi:10.1007/s00439-006-0242-x · Cited by 54 · see citing works
Self-citationClinical, MRI, and pathological features of polymicrogyria in chromosome 22q11 deletion syndrome
Sztriha, L., Guerrini, R., Harding, B. N., Stewart, F. A., Chelloug, N., & Johansen, J. G. (2004) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30014 · Cited by 54 · see citing works
Periventricular nodular heterotopia and Williams syndrome
Ferland, R. J., Gaitanis, J. N., Apse, K. A., Tantravahi, U., Walsh, C. A., & Sheen, V. L. (2006) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31259 · Cited by 54 · see citing works
Dissection of Tbx1 and Fgf interactions in mouse models of 22q11DS suggests functional redundancy
Aggarwal, V. S., Liao, J., Bondarev, A., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl399 · Cited by 54 · see citing works
Steinberger, D., Reinhartz, T., Unsöld, R., & Müller, U. (1996) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19961202)66:1 · Cited by 51 · see citing works
Rioux, L., & Arnold, S. E. (2005) · Psychiatry Research · doi:10.1016/j.psychres.2004.11.003 · Cited by 51 · see citing works
Shashi, V., Muddasani, S., dos Santos, C. C., Berry, M. N., Kwapil, T. R., Lewandowski, K. E., & Keshavan, M. S. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2003.12.004 · Cited by 50 · see citing works
Gene dosage in the developing and adult brain in a mouse model of 22q11 deletion syndrome
Meechan, D. W., Maynard, T. M., Wu, Y., Gopalakrishna, D., Lieberman, J. A., & LaMantia, A. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2006.09.001 · Cited by 48 · see citing works
Corpus callosum morphology and ventricular size in chromosome 22q11.2 deletion syndrome
Machado, A. M. C., Simon, T. J., Nguyen, V., McDonald‐McGinn, D. M., Zackai, E. H., & Gee, J. C. (2006) · Brain Research · doi:10.1016/j.brainres.2006.10.082 · Cited by 48 · see citing works
Size of hippocampal pyramidal neurons in schizophrenia
Highley, J. R., Walker, M. A., McDonald, B., Crow, T. J., & Esiri, M. M. (2003) · The British Journal of Psychiatry · doi:10.1192/bjp.183.5.414 · Cited by 46 · see citing works
Sivagnanasundaram, S., Fletcher, D., Hubank, M. J. F., Illingworth, E. A., Skuse, D., & Scambler, P. J. (2007) · Brain Research · doi:10.1016/j.brainres.2007.01.014 · Cited by 39 · see citing works
Hereditary Vascular Dementia Linked to Notch 3 Mutations: CADASIL in British Families
Thomas, N., Morris, C. M., Scaravilli, F., JOHANSSON, J., Rossor, M. N., LANGE, R. D., Clair, D. S., Nicoll, J. A. R., Blank, C., Coulthard, A., et al. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06379.x · Cited by 34 · see citing works
Cortical dysgenesis in 2 patients with chromosome 22q11 deletion
Bird, L. M., & Scambler, P. J. (2000) · Clinical Genetics · doi:10.1034/j.1399-0004.2000.580111.x · Cited by 29 · see citing works
Patterns of dysmorphic features in schizophrenia
Scutt, L. E., Chow, E. W. C., Weksberg, R., et al. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1612 · Cited by 24 · see citing works
Self-citationKoolen, D. A., Veltman, J. A., Renier, W. O., Droog, R. P., van Kessel, A. G., & Vries, B. B. A. D. (2004) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30377 · Cited by 16 · see citing works
Nopoulos, P., Swayze, V. W., Flaum, M. A., & Andreasen, N. C. (1998) · Journal of Neuropsychiatry · doi:10.1176/jnp.10.3.351 · Cited by 13 · see citing works
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- Authors
- Kiehl, T. R., Chow, E. W. C., Mikulis, D. J., George, S. R., & Bassett, A. S.
- Affiliations
- University Health Network (CA)
- Centre for Addiction and Mental Health (CA)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-05-14
- Volume
- 19
- Issue
- 1
- Pages
- 153-164
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2131053422
- Cited by
- 76
- References
- 51
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 10 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 6 · 2015: 8 · 2014: 9 · 2013: 7 · 2012: 3
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- 22q11.2 deletion syndrome, schizophrenia, neuropathology, periventricular nodular heterotopia, astrocytic gliosis, cerebrovascular pathology, polymicrogyria, white matter abnormalities, microdeletion syndromes, adult brain
- MeSH terms
- Adult, Brain, DiGeorge Syndrome, Female, Humans, Male, Middle Aged, Nerve Fibers, Myelinated, Neurons, Schizophrenia
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