Skip to main content

Advertisement

SpringerLink
Log in

Cognitive, Behavioural and Psychiatric Phenotype in 22q11.2 Deletion Syndrome

  • Original Research
  • Published:
Behavior Genetics Aims and scope Submit manuscript

Abstract

22q11.2 Deletion syndrome has become an important model for understanding the pathophysiology of neurodevelopmental conditions, particularly schizophrenia which develops in about 20–25% of individuals with a chromosome 22q11.2 microdeletion. From the initial discovery of the syndrome, associated developmental delays made it clear that changes in brain development were a key part of the expression. Once patients were followed through childhood into adult years, further neurobehavioural phenotypes became apparent, including a changing cognitive profile, anxiety disorders and seizure diathesis. The variability of expression is as wide as for the myriad physical features associated with the syndrome, with the addition of evolving phenotype over the developmental trajectory. Notably, variability appears unrelated to length of the associated deletion. Several mouse models of the deletion have been engineered and are beginning to reveal potential molecular mechanisms for the cognitive and behavioural phenotypes observable in animals. Both animal and human studies hold great promise for further discoveries relevant to neurodevelopment and associated cognitive, behavioural and psychiatric disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Abou Jamra R, Schumacher J, Becker T, Dahdouh F, Ohlraun S, Suliman H, Schulze TG, Tullius M, Kovalenko S, Maier W, Rietschel M, Propping P, Nöthen MM, Cichon S (2005) No evidence for an association between variants at the proline dehydrogenase locus and schizophrenia or bipolar affective disorder. Psychiatr Genet 15:195–198

    Article  PubMed  Google Scholar 

  • Antshel KM, Shprintzen R, Fremont W, Higgins AM, Faraone SV, Kates WR (2010) Cognitive and psychiatric predictors to psychosis in velocardiofacial syndrome: a 3-year follow-up study. J Am Acad Child Adolesc Psychiatry 49:333–344

    PubMed  Google Scholar 

  • Baker K, Baldeweg T, Sivagnanasundaram S, Scambler P, Skuse D (2005) COMT Val108/158 Met modifies mismatch negativity and cognitive function in 22q11 deletion syndrome. Biol Psychiatry 58:23–31

    Article  PubMed  Google Scholar 

  • Bassett AS, Chow EW (2008) Schizophrenia and 22q11.2 deletion syndrome. Curr Psychiatry Rep 10:148–157

    Article  PubMed  Google Scholar 

  • Bassett AS, Chow EW, AbdelMalik P, Gheorghiu M, Husted J, Weksberg R (2003) The schizophrenia phenotype in 22q11 deletion syndrome. Am J Psychiatry 160:1580–1586

    Article  PubMed  Google Scholar 

  • Bassett AS, Chow EW, Husted J, Weksberg R, Caluseriu O, Webb GD, Gatzoulis MA (2005) Clinical features of 78 adults with 22q11 deletion syndrome. Am J Med Genet Part A 138:307–313

    PubMed  Google Scholar 

  • Bassett AS, Caluseriu O, Weksberg R, Young DA, Chow EW (2007) Catechol-o-methyl transferase and expression of schizophrenia in 73 adults with 22q11 deletion syndrome. Biol Psychiatry 61:1135–1140

    Article  PubMed  Google Scholar 

  • Bassett AS, Marshall CR, Lionel AC, Chow EW, Scherer SW (2008) Copy number variations and risk for schizophrenia in 22q11.2 deletion syndrome. Hum Mol Genet 17:4045–4053

    Article  PubMed  Google Scholar 

  • Bassett AS, Costain G, Fung WLA, Russell KJ, Pierce L, Kapadia R, Carter RF, Chow EW, Forsythe PJ (2010) Clinically detectable copy number variations in a Canadian catchment population of schizophrenia. J Psychiatr Res 44:1005–1009

    Article  PubMed  Google Scholar 

  • Bearden CE, Wang PP, Simon TJ (2002) Williams syndrome cognitive profile also characterizes Velocardiofacial/DiGeorge syndrome. Am J Med Genet 114:689–692

    Article  PubMed  Google Scholar 

  • Bearden CE, Jawad AF, Lynch DR, Sokol S, Kanes SJ, McDonald-McGinn DM, Saitta SC, Harris SE, Moss E, Wang PP, Zackai E, Emanuel BS, Simon TJ (2004) Effects of a functional COMT polymorphism on prefrontal cognitive function in patients with 22q11.2 deletion syndrome. Am J Psychiatry 161:1700–1702

    Article  PubMed  Google Scholar 

  • Bearden CE, van Erp TG, Dutton RA, Lee AD, Simon TJ, Cannon TD, Emanuel BS, McDonald-McGinn D, Zackai EH, Thompson PM (2009) Alterations in midline cortical thickness and gyrification patterns mapped in children with 22q11.2 deletions. Cereb Cortex 19:115–126

    Article  PubMed  Google Scholar 

  • Booij J, van Amelsvoort T, Boot E (2010) Co-occurrence of early-onset Parkinson disease and 22q11.2 deletion syndrome: potential role for dopamine transporter imaging. Am J Med Genet A 152A:2937–2938

    Article  PubMed  Google Scholar 

  • Bruining H, de Sonneville L, Swaab H, de Jonge M, Kas M, van Engeland H, Vorstman J (2010) Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes. PLoS One 5:e10887

    Article  PubMed  Google Scholar 

  • Chen HY, Yeh JI, Hong CJ, Chen CH (2005) Mutation analysis of ARVCF gene on chromosome 22q11 as a candidate for a schizophrenia gene. Schizophr Res 72:275–277

    Article  PubMed  Google Scholar 

  • Chow EW, Watson M, Young DA, Bassett AS (2006) Neurocognitive profile in 22q11 deletion syndrome and schizophrenia. Schizophr Res 87:270–278

    Article  PubMed  Google Scholar 

  • Chow EWC, Ho A, Wei C, Voormolen EHJ, Crawley A, Bassett AS (2011) Association of schizophrenia in 22q11.2 deletion syndrome and gray matter volumetric deficits in the superior temporal gyrus. Am J Psychiatry 168:522–529

    Article  PubMed  Google Scholar 

  • Costas J, Sanjuan J, Ramos-Rios R, Paz E, Agra S, Ivorra JL, Paramo M, Brenlla J, Arrojo M (2011) Heterozygosity at catechol-o-methyltransferase Val158Met and schizophrenia: new data and meta-analysis. J Psychiatr Res 45(1):7–14

    Article  PubMed  Google Scholar 

  • De Luca A, Pasini A, Amati F, Botta A, Spalletta G, Alimenti S, Caccamo F, Conti E, Trakalo J, Macciardi F, Dallapiccola B, Novelli G (2001) Association study of a promoter polymorphism of UFD1L gene with schizophrenia. Am J Med Genet 105:529–533

    Article  PubMed  Google Scholar 

  • De Smedt B, Swillen A, Verschaffel L, Ghesquiere P (2009) Mathematical learning disabilities in children with 22q11.2 deletion syndrome: a review. Dev Disabil Res Rev 15:4–10

    Article  PubMed  Google Scholar 

  • Earls LR, Bayazitov IT, Fricke RG, Berry RB, Illingworth E, Mittleman G, Zakharenko SS (2010) Dysregulation of presynaptic calcium and synaptic plasticity in a mouse model of 22q11 deletion syndrome. J Neurosci 30:15843–15855

    Article  PubMed  Google Scholar 

  • Edelmann L, Pandita RK, Morrow BE (1999) Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome. Am J Hum Genet 64:1076–1086

    Article  PubMed  Google Scholar 

  • Ensenauer RE, Adeyinka A, Flynn HC, Michels VV, Lindor NM, Dawson DB, Thorland EC, Lorentz CP, Goldstein JL, McDonald MT, Smith WE, Simon-Fayard E, Alexander AA, Kulharya AS, Ketterling RP, Clark RD, Jalal SM (2003) Microduplication 22q11.2, an emerging syndrome: clinical, cytogenetic, and molecular analysis of thirteen patients. Am J Hum Genet 73:1027–1040

    Article  PubMed  Google Scholar 

  • Fan JB, Ma J, Zhang CS, Tang JX, Gu NF, Feng GY, St Clair D, He L (2003) A family-based association study of T1945C polymorphism in the proline dehydrogenase gene and schizophrenia in the Chinese population. Neurosci Lett 338:252–254

    Article  PubMed  Google Scholar 

  • Fung WL, McEvilly R, Fong J, Silversides C, Chow E, Bassett A (2010) Elevated prevalence of generalized anxiety disorder in adults with 22q11.2 deletion syndrome. Am J Psychiatry 167:998

    Article  PubMed  Google Scholar 

  • Funke BH, Lencz T, Finn CT, DeRosse P, Poznik GD, Plocik AM, Kane J, Rogus J, Malhotra AK, Kucherlapati R (2007) Analysis of TBX1 variation in patients with psychotic and affective disorders. Mol Med 13:407–414

    Article  PubMed  Google Scholar 

  • Gerdes M, Solot C, Wang PP, McDonald-McGinn DM, Zackai EH (2001) Taking advantage of early diagnosis: preschool children with the 22q11.2 deletion. Genet Med 3:40–44

    Article  PubMed  Google Scholar 

  • Glaser B, Debbane M, Hinard C, Morris MA, Dahoun SP, Antonarakis SE, Eliez S (2006a) No evidence for an effect of COMT Val158Met genotype on executive function in patients with 22q11 deletion syndrome. Am J Psychiatry 163:537–539

    Article  PubMed  Google Scholar 

  • Glaser B, Moskvina V, Kirov G, Murphy KC, Williams H, Williams N, Owen MJ, O’Donovan MC (2006b) Analysis of PRODH, COMT and ZDHHC8 risk variants does not support individual or interactive effects on schizophrenia susceptibility. Schizophr Res 87:21–27

    Article  PubMed  Google Scholar 

  • Gogos JA, Morgan M, Luine V, Santha M, Ogawa S, Pfaff D, Karayiorgou M (1998) Catechol-o-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behaviour. Proc Natl Acad Sci 95:9991–9996

    Article  PubMed  Google Scholar 

  • Gogos A, van den Buuse M, Rossell S (2009) Gender differences in prepulse inhibition (PPI) in bipolar disorder: men have reduced PPI, women have increased PPI. Int J Neuropsychopharmacol 12:1249–1259

    Article  PubMed  Google Scholar 

  • Goodship J, Cross I, LiLing J, Wren C (1998) A population study of chromosome 22q11 deletions in infancy. Arch Dis Child 79:348–351

    Article  PubMed  Google Scholar 

  • Gothelf D, Eliez S, Thompson T, Hinard C, Penniman L, Feinstein C, Kwon H, Jin S, Jo B, Antonarakis SE, Morris MA, Reiss AL (2005) COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome. Nat Neurosci 8:1500–1502

    Article  PubMed  Google Scholar 

  • Green T, Gothelf D, Glaser B, Debbane M, Frisch A, Kotler M, Weizman A, Eliez S (2009) Psychiatric disorders and intellectual functioning throughout development in velocardiofacial (22q11.2 deletion) syndrome. J Am Acad Child Adolesc Psychiatry 48:1060–1068

    Article  PubMed  Google Scholar 

  • Guyot L, Dubuc M, Pujol J, Dutour O, Philip N (2001) Craniofacial anthropometric analysis in patients with 22q11 microdeletion. Am J Med Genet 100:1–8

    Article  PubMed  Google Scholar 

  • Hsu R, Woodroffe A, Lai WS, Cook MN, Mukai J, Dunning JP, Swanson DJ, Roos JL, Abecasis GR, Karayiorgou M, Gogos JA (2007) Nogo Receptor 1 (RTN4R) as a candidate gene for schizophrenia: analysis using human and mouse genetic approaches. PLoS One 2:e1234

    Article  PubMed  Google Scholar 

  • Ikeda M, Williams N, Williams HJ, Smith R, Monks S, Owen MJ, Murphy KC, O’Donovan MC (2010) Failure to confirm association between PIK4CA and psychosis in 22q11.2 deletion syndrome. Am J Med Genet B 153B:980–982

    Google Scholar 

  • Insel TR (2010) Rethinking schizophrenia. Nature 468:187–193

    Article  PubMed  Google Scholar 

  • Jacobson C, Shearer J, Habel A, Kane F, Tsakanikos E, Kravariti E (2010) Core neuropsychological characteristics of children and adolescents with 22q11.2 deletion. J Intellect Disabil Res 54:701–713

    Article  PubMed  Google Scholar 

  • Jerome LA, Papaioannou VE (2001) DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1. Nat Genet 27:286–291

    Article  PubMed  Google Scholar 

  • Jungerius BJ, Hoogendoorn ML, Bakker SC, Van’t Slot R, Bardoel AF, Ophoff RA, Wijmenga C, Kahn RS, Sinke RJ (2008) An association screen of myelin-related genes implicates the chromosome 22q11 PIK4CA gene in schizophrenia. Mol Psychiatry 13:1060–1068

    Article  PubMed  Google Scholar 

  • Jurata LW, Gallagher P, Lemire AL, Charles V, Brockman JA, Illingworth EL, Altar CA (2006) Altered expression of hippocampal dentate granule neuron genes in a mouse model of human 22q11 deletion syndrome. Schizophr Res 88:251–259

    Article  PubMed  Google Scholar 

  • Kates WR, Antshel KM, Abdulsabur N, Colgan D, Funke B, Fremont W, Higgins AM, Kucherlapati R, Shprintzen RJ (2006) A gender-moderated effect of a functional COMT polymorphism on prefrontal brain morphology and function in velo-cardio-facial syndrome (22q11.2 deletion syndrome). Am J Med Genet B 141B:274–280

    Article  Google Scholar 

  • Kempf L, Nicodemus KK, Kolachana B, Vakkalanka R, Verchinski BA, Egan MF, Straub RE, Mattay VA, Callicott JH, Weinberger DR, Meyer-Lindenberg A (2008) Functional polymorphisms in PRODH are associated with risk and protection for schizophrenia and fronto-striatal structure and function. PLoS Genet 4:e1000252

    Article  PubMed  Google Scholar 

  • Kiehl TR, Chow EWC, Mikulis DJ, George SR, Bassett AS (2009) Neuropathologic features in adults with 22q11.2 deletion syndrome. Cereb Cortex 19:153–164

    Article  PubMed  Google Scholar 

  • Kimber WL, Hsieh P, Hirotsune S, Yuva-Paylor L, Sutherland HF, Chen A, Ruiz-Lozano P, Hoogstraten-Miller SL, Chien KR, Paylor R, Scambler PJ, Wynshaw-Boris A (1999) Deletion of 150 kb in the minimal DiGeorge/velocardiofacial syndrome critical region in mouse. Hum Mol Genet 8:2229–2237

    Article  PubMed  Google Scholar 

  • Kobrynski LJ, Sullivan KE (2007) Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet 370:1443–1452

    Article  PubMed  Google Scholar 

  • Kumar D (2008) Disorders of the genome architecture: a review. Genomic Med 2:69–76

    Article  PubMed  Google Scholar 

  • Li T, Ma X, Sham PC, Sun X, Hu X, Wang Q, Meng H, Deng W, Liu X, Murray RM, Collier DA (2004) Evidence for association between novel polymorphisms in the PRODH gene and schizophrenia in a Chinese population. Am J Med Genet B 129B:13–15

    Article  Google Scholar 

  • Lindsay EA, Baldini A (2001) Recovery from arterial growth delay reduces penetrance of cardiovascular defects in mice deleted for the DiGeorge syndrome region. Hum Mol Genet 10:997–1002

    Article  PubMed  Google Scholar 

  • Lindsay EA, Botta A, Jurecic V, Carattini-Rivera S, Cheah YC, Rosenblatt HM, Bradley A, Baldini A (1999) Congenital heart disease in mice deficient for the DiGeorge syndrome region. Nature 401:379–383

    PubMed  Google Scholar 

  • Lindsay EA, Vitelli F, Su H, Morishima M, Huynh T, Pramparo T, Jurecic V, Ogunrinu G, Sutherland HF, Scambler PJ, Bradley A, Baldini A (2001) Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Nature 410:97–101

    Article  PubMed  Google Scholar 

  • Liu H, Abecasis GR, Heath SC, Knowles A, Demars S, Chen YJ, Roos JL, Rapoport JL, Gogos JA, Karayiorgou M (2002) Genetic variation in the 22q11 locus and susceptibility to schizophrenia. Proc Natl Acad Sci 99:16859–16864

    Article  PubMed  Google Scholar 

  • Long JM, LaPorte P, Merscher S, Funke B, Saint-Jore B, Puech A, Kucherlapati R, Morrow BE, Skoultchi AI, Wynshaw-Boris A (2006) Behaviour of mice with mutations in the conserved region deleted in velocardiofacial/DiGeorge syndrome. Neurogenetics 7:247–257

    Article  PubMed  Google Scholar 

  • Ma G, Shi Y, Tang W, He Z, Huang K, Li Z, He G, Feng G, Li H, He L (2007) An association study between the genetic polymorphisms within TBX1 and schizophrenia in the Chinese population. Neurosci Lett 425:146–150

    Article  PubMed  Google Scholar 

  • Mas S, Bernardo M, Gasso P, Alvarez S, Garcia-Rizo C, Bioque M, Kirkpatrick B, Lafuente A (2010) A functional variant provided further evidence for the association of ARVCF with schizophrenia. Am J Med Genet B 153B:1052–1059

    Google Scholar 

  • Maynard TM, Haskell GT, Peters AZ, Sikich L, Lieberman JA, LaMantia AS (2003) A comprehensive analysis of 22q11 gene expression in the developing and adult brain. Proc Natl Acad Sci 100:14433–14438

    Article  PubMed  Google Scholar 

  • Meechan DW, Tucker ES, Maynard TM, LaMantia AS (2009) Diminished dosage of 22q11 genes disrupts neurogenesis and cortical development in a mouse model of 22q11 deletion/DiGeorge syndrome. Proc Natl Acad Sci 106:16434–16445

    Article  PubMed  Google Scholar 

  • Meechan DW, Maynard TM, Tucker ES and Lamantia AS (2010) Three phases of DiGeorge/22q11 deletion syndrome pathogenesis during brain development: patterning, proliferation, and mitochondrial functions of 22q11 genes. Int J Dev Neurosci (in press)

  • Merscher S, Funke B, Epstein JA, Heyer J, Puech A, Lu MM, Xavier RJ, Demay MB, Russell RG, Factor S, Tokooya K, Jore BS, Lopez M, Pandita RK, Lia M, Carrion D, Xu H, Schorle H, Kobler JB, Scambler P, Wynshaw-Boris A, Skoultchi AI, Morrow BE, Kucherlapati R (2001) TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell 104:619–629

    Article  PubMed  Google Scholar 

  • Mukai J, Liu H, Burt RA, Swor DE, Lai WS, Karayiorgou M, Gogos JA (2004) Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia. Nat Genet 36:725–731

    Article  PubMed  Google Scholar 

  • Mukai J, Dhilla A, Drew LJ, Stark KL, Cao L, MacDermott AB, Karayiorgou M, Gogos JA (2008) Palmitoylation-dependent neurodevelopmental deficits in a mouse model of 22q11 microdeletion. Nat Neurosci 11:1302–1310

    Article  PubMed  Google Scholar 

  • Murphy KC, Jones LA, Owen MJ (1999) High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry 56:940–945

    Article  PubMed  Google Scholar 

  • Niklasson L, Rasmussen P, Oskarsdottir S, Gillberg C (2009) Autism, ADHD, mental retardation and behaviour problems in 100 individuals with 22q11 deletion syndrome. Res Dev Disabil 30:763–773

    Article  PubMed  Google Scholar 

  • Ohtsuki T, Tanaka S, Ishiguro H, Noguchi E, Arinami T, Tanabe E, Yara K, Okubo T, Takahashi S, Matsuura M, Sakai T, Muto M, Kojima T, Matsushima E, Toru M, Inada T (2004) Failure to find association between PRODH deletion and schizophrenia. Schizophr Res 67:111–113

    Article  PubMed  Google Scholar 

  • Otani K, Ujike H, Tanaka Y, Morita Y, Kishimoto M, Morio A, Uchida N, Nomura A, Kuroda S (2005) The ZDHHC8 gene did not associate with bipolar disorder or schizophrenia. Neurosci Lett 390:166–170

    Article  PubMed  Google Scholar 

  • Paterlini M, Zakharenko SS, Lai WS, Qin J, Zhang H, Mukai J, Westphal KG, Olivier B, Sulzer D, Pavlidis P, Siegelbaum SA, Karayiorgou M, Gogos JA (2005) Transcriptional and behavioural interaction between 22q11.2 orthologs modulates schizophrenia-related phenotypes in mice. Nat Neurosci 8:1586–1594

    Article  PubMed  Google Scholar 

  • Paylor R, Lindsay E (2006) Mouse models of 22q11 deletion syndrome. Biol Psychiatry 59:1172–1179

    Article  PubMed  Google Scholar 

  • Paylor R, McIlwain KL, McAninch R, Nellis A, Yuva-Paylor LA, Baldini A, Lindsay EA (2001) Mice deleted for the DiGeorge/velocardiofacial syndrome region show abnormal sensorimotor gating and learning and memory impairments. Hum Mol Genet 10:2645–2650

    Article  PubMed  Google Scholar 

  • Paylor R, Glaser B, Mupo A, Ataliotis P, Spencer C, Sobotka A, Sparks C, Choi CH, Oghalai J, Curran S, Murphy KC, Monks S, Williams N, O’Donovan MC, Owen MJ, Scambler PJ, Lindsay E (2006) Tbx1 haploinsufficiency is linked to behavioural disorders in mice and humans: implications for 22q11 deletion syndrome. Proc Natl Acad Sci 103:7729–7734

    Article  PubMed  Google Scholar 

  • Portnoi MF (2009) Microduplication 22q11.2: a new chromosomal syndrome. Eur J Med Genet 52:88–93

    Article  PubMed  Google Scholar 

  • Prasad SE, Howley S, Murphy KC (2008) Candidate genes and the behavioral phenotype in 22q11.2 deletion syndrome. Dev Disabil Res Rev 14:26–34

    Article  PubMed  Google Scholar 

  • Puech A, Saint-Jore B, Funke B, Gilbert DJ, Sirotkin H, Copeland NG, Jenkins NA, Kucherlapati R, Morrow B, Skoultchi AI (1997) Comparative mapping of the human 22q11 chromosomal region and the orthologous region in mice reveals complex changes in gene organization. Proc Natl Acad Sci 94:14608–14613

    Article  PubMed  Google Scholar 

  • Rauch A, Devriendt K, Koch A, Rauch R, Gewillig M, Kraus C, Weyand M, Singer H, Reis A, Hofbeck M (2004) Assessment of association between variants and haplotypes of the remaining TBX1 gene and manifestations of congenital heart defects in 22q11.2 deletion patients. J Med Genet 41:e40

    Article  PubMed  Google Scholar 

  • Raux G, Bumsel E, Hecketsweiler B, van Amelsvoort T, Zinkstok J, Manouvrier-Hanu S, Fantini C, Breviere GM, Di Rosa G, Pustorino G, Vogels A, Swillen A, Legallic S, Bou J, Opolczynski G, Drouin-Garraud V, Lemarchand M, Philip N, Gerard-Desplanches A, Carlier M, Philippe A, Nolen MC, Heron D, Sarda P, Lacombe D, Coizet C, Alembik Y, Layet V, Afenjar A, Hannequin D, Demily C, Petit M, Thibaut F, Frebourg T, Campion D (2007) Involvement of hyperprolinemia in cognitive and psychiatric features of the 22q11 deletion syndrome. Hum Mol Genet 16:83–91

    Article  PubMed  Google Scholar 

  • Robin NH, Taylor CJ, McDonald-McGinn DM, Zackai EH, Bingham P, Collins KJ, Earl D, Gill D, Granata T, Guerrini R, Katz N, Kimonis V, Lin JP, Lynch DR, Mohammed SN, Massey RF, McDonald M, Rogers RC, Splitt M, Stevens CA, Tischkowitz MD, Stoodley N, Leventer RJ, Pilz DT, Dobyns WB (2006) Polymicrogyria and deletion 22q11.2 syndrome: window to the etiology of a common cortical malformation. Am J Med Genet A 140:2416–2425

    PubMed  Google Scholar 

  • Roizen NJ, Antshel KM, Fremont W, AbdulSabur N, Higgins AM, Shprintzen RJ, Kates WR (2007) 22q11.2DS deletion syndrome: developmental milestones in infants and toddlers. J Dev Behav Pediatr 28:119–124

    Article  PubMed  Google Scholar 

  • Ryan AK, Goodship JA, Wilson DI, Philip N, Levy A, Seidel H, Schuffenhauer S, Oechsler H, Belohradsky B, Prieur M, Aurias A, Raymond FL, Clayton-Smith J, Hatchwell E, McKeown C, Beemer FA, Dallapiccola B, Novelli G, Hurst JA, Ignatius J, Green AJ, Winter RM, Brueton L, Brondum-Nielsen K, Scambler PJ et al (1997) Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet 34:798–804

    Article  PubMed  Google Scholar 

  • Saito S, Ikeda M, Iwata N, Suzuki T, Kitajima T, Yamanouchi YYK, Takahashi N, Inada T, Ozaki N (2005) No association was found between a functional SNP in ZDHHC8 and schizophrenia in a Japanese case-control population. Neurosci Lett 374:21–24

    Article  PubMed  Google Scholar 

  • Scambler PJ (2000) The 22q11 deletion syndromes. Hum Mol Genet 9:2421–2426

    Article  PubMed  Google Scholar 

  • Schaer M, Debbane M, Bach Cuadra M, Ottet MC, Glaser B, Thiran JP, Eliez S (2009) Deviant trajectories of cortical maturation in 22q11.2 deletion syndrome (22q11.2DS): a cross-sectional and longitudinal study. Schizophr Res 115:182–190

    Article  PubMed  Google Scholar 

  • Shaikh TH, Kurahashi H, Saitta SC, O’Hare AM, Hu P, Roe BA, Driscoll DA, McDonald-McGinn DM, Zackai EH, Budarf ML, Emanuel BS (2000) Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis. Hum Mol Genet 9:489–501

    Article  PubMed  Google Scholar 

  • Shashi V, Keshavan MS, Howard TD, Berry MN, Basehore MJ, Lewandowski E, Kwapil TR (2006) Cognitive correlates of a functional COMT polymorphism in children with 22q11.2 deletion syndrome. Clin Genet 69:234–238

    Article  PubMed  Google Scholar 

  • Shashi V, Kwapil TR, Kaczorowski J, Berry MN, Santos CS, Howard TD, Goradia D, Prasad K, Vaibhav D, Rajarethinam R, Spence E, Keshavan MS (2010) Evidence of gray matter reduction and dysfunction in chromosome 22q11.2 deletion syndrome. Psychiatry Res 181:1–8

    Article  PubMed  Google Scholar 

  • Sivagnanasundaram S, Fletcher D, Hubank M, Illingworth E, Skuse D, Scambler P (2007) Differential gene expression in the hippocampus of the Df1/+ mice: a model for 22q11.2 deletion syndrome and schizophrenia. Brain Res 1139:48–59

    Article  PubMed  Google Scholar 

  • Sobin C, Monk SH, Kiley-Brabeck K, Khuri J, Karayiorgou M (2006) Neuromotor deficits in children with the 22q11 deletion syndrome. Mov Disord 21:2082–2089

    Article  PubMed  Google Scholar 

  • Stark KL, Xu B, Bagchi A, Lai WS, Liu H, Hsu R, Wan X, Pavlidis P, Mills AA, Karayiorgou M, Gogos JA (2008) Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. Nat Genet 40:751–760

    Article  PubMed  Google Scholar 

  • Suzuki G, Harper KM, Hiramoto T, Sawamura T, Lee M, Kang G, Tanigaki K, Buell M, Geyer MA, Trimble WS, Agatsuma S, Hiroi N (2009) SEPT5 deficiency exerts pleiotropic influence on affective behaviours and cognitive functions in mice. Hum Mol Genet 18:1652–1660

    Article  PubMed  Google Scholar 

  • Swillen A, Devriendt K, Legius E, Prinzie P, Vogels A, Ghesquiere P, Fryns JP (1999) The behavioural phenotype in velo-cardio-facial syndrome (VCFS): from infancy to adolescence. Genet Couns 10:79–88

    PubMed  Google Scholar 

  • Swillen A, Vogels A, Devriendt K, Fryns JP (2000) Chromosome 22q11 deletion syndrome: update and review of the clinical features, cognitive-behavioural spectrum, and psychiatric complications. Am J Med Genet 97:128–135

    Article  PubMed  Google Scholar 

  • Torres-Juan L, Rosell J, Sanchez-de-la-Torre M, Fibla J, Heine-Suner D (2007) Analysis of meiotic recombination in 22q11.2, a region that frequently undergoes deletions and duplications. BMC Med Genet 8:14

    Article  PubMed  Google Scholar 

  • van Amelsvoort T, Henry J, Morris R, Owen M, Linszen D, Murphy K, Murphy D (2004) Cognitive deficits associated with schizophrenia in velo-cardio-facial syndrome. Schizophr Res 70:223–232

    Article  PubMed  Google Scholar 

  • van Amelsvoort T, Zinkstok J, Figee M, Daly E, Morris R, Owen MJ, Murphy KC, De Haan L, Linszen DH, Glaser B, Murphy DG (2008) Effects of a functional COMT polymorphism on brain anatomy and cognitive function in adults with velo-cardio-facial syndrome. Psychol Med 38:89–100

    PubMed  Google Scholar 

  • Voelckel MA, Girardot L, Giusiano B, Levy N, Philip N (2004) Allelic variations at the haploid TBX1 locus do not influence the cardiac phenotype in cases of 22q11 microdeletion. Ann Genet 47:235–240

    PubMed  Google Scholar 

  • Vorstman JA, Morcus ME, Duijff SN, Klaassen PW, Heineman-de Boer JA, Beemer FA, Swaab H, Kahn RS, van Engeland H (2006) The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. J Am Acad Child Adolesc Psychiatry 45:1104–1113

    Article  PubMed  Google Scholar 

  • Vorstman JA, Chow EW, Ophoff RA, van Engeland H, Beemer FA, Kahn RS, Sinke RJ, Bassett AS (2009a) Association of the PIK4CA schizophrenia-susceptibility gene in adults with the 22q11.2 deletion syndrome. Am J Med Genet B 150B:430–433

    Article  Google Scholar 

  • Vorstman JA, Turetsky BI, Sijmens-Morcus ME, de Sain MG, Dorland B, Sprong M, Rappaport EF, Beemer FA, Emanuel BS, Kahn RS, van Engeland H, Kemner C (2009b) Proline affects brain function in 22q11.2DS children with the low activity COMT 158 allele. Neuropsychopharmacology 34:739–746

    Article  PubMed  Google Scholar 

  • Williams HJ, Williams N, Spurlock G, Norton N, Zammit S, Kirov G, Owen MJ, O’Donovan MC (2003) Detailed analysis of PRODH and PsPRODH reveals no association with schizophrenia. Am J Med Genet B 120B:42–46

    Article  Google Scholar 

  • Xu M, St Clair D, He L (2010) Testing for genetic association between the ZDHHC8 gene locus and susceptibility to schizophrenia: an integrated analysis of multiple datasets. Am J Med Genet B 153B:1266–1275

    Article  Google Scholar 

  • Yagi H, Furutani Y, Hamada H, Sasaki T, Asakawa S, Minoshima S, Ichida F, Joo K, Kimura M, Imamura S, Kamatani N, Momma K, Takao A, Nakazawa M, Shimizu N, Matsuoka R (2003) Role of TBX1 in human del22q11.2 syndrome. Lancet 362:1366–1373

    Article  PubMed  Google Scholar 

  • Zaleski C, Bassett AS, Tam K, Shugar AL, Chow EW, McPherson E (2009) The co-occurrence of early onset Parkinson disease and 22q11.2 deletion syndrome. Am J Med Genet A 149A:525–528

    Article  PubMed  Google Scholar 

  • Zweier C, Sticht H, Aydin-Yaylagul I, Campbell CE, Rauch A (2007) Human TBX1 missense mutations cause gain of function resulting in the same phenotype as 22q11.2 deletions. Am J Hum Genet 80:510–517

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Multidisciplinary Center for Prenatal Diagnosis, La Timone Children’s Hospital, AP-HM, Marseilles, France

    Nicole Philip

  2. Department of Medical Genetics, La Timone Children’s Hospital, AP-HM, Marseilles, France

    Nicole Philip

  3. Clinical Genetics Research Program, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON, M5S 2S1, Canada

    Anne Bassett

  4. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Anne Bassett

  5. Division of Cardiology, Department of Medicine, University Health Network, Toronto, ON, Canada

    Anne Bassett

Authors
  1. Nicole Philip
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne Bassett
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne Bassett.

Additional information

Edited by Petrus de Vries and Pierre Roubertoux.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Philip, N., Bassett, A. Cognitive, Behavioural and Psychiatric Phenotype in 22q11.2 Deletion Syndrome. Behav Genet 41, 403–412 (2011). https://doi.org/10.1007/s10519-011-9468-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10519-011-9468-z

Keywords

Search

Navigation