PDF herunterladen
Neuropediatrics 2011; 42(06): 215-221
DOI: 10.1055/s-0031-1295479
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Neuroradiological and Neurofunctional Examinations for Patients with 22q11.2 Deletion

T. Mori
1   Department of Pediatrics, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan
,
K. Mori
1   Department of Pediatrics, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan
,
E Fujii
1   Department of Pediatrics, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan
,
Y. Toda
1   Department of Pediatrics, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan
,
M. Miyazaki
1   Department of Pediatrics, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan
,
M. Harada
2   Department of Radiology, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan
,
S. Kagami
1   Department of Pediatrics, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 20. Juni 2011

accepted 31. Oktober 2011

Publikationsdatum:
30. November 2011 (online)

    Lizenzen und Reprints

Abstract

Since the neuroradiological features of patients with 22q11.2 deletion syndrome are not well-understood, examinations using functional imaging were performed in this study. Brain magnetic resonance imaging (MRI) and 1H-magnetic resonance spectroscopy (MRS) were performed using a clinical 3-Tesla MR imager in 4 patients with 22q11.2 deletion syndrome (2 boys and 2 girls; aged 2–6 years.) and 20 age- and sex-matched healthy control subjects. Furthermore, interictal 123I-iomazenil (IMZ) single photon emission computed tomography (SPECT) was examined in 2 of the 4 patients. Among the 4 patients with 22q11.2 deletion syndrome, 2 patients showed polymicrogyria and 1 patient showed agyria. Those patients with brain malformations also showed abnormal brain artery patterns and decreased accumulation of IMZ in 123I-IMZ SPECT. Although all 4 patients showed epileptic discharges in their electroencephalograms (EEG), one patient with polymicrogyria had no seizure episodes. Decreases in γ-aminobutyric acid (GABA) corresponding to the areas of polymicrogyria and/or epileptic discharges in EEG were shown in all patients except for the patient with agyria. Although consistent evidence was not seen in patients with 22q11.2 deletion syndrome in this study, brain malformations and disturbances of the GABAergic nervous system would be underlying mechanisms of the neurodevelopmental abnormalities in this syndrome.

Key words

123I-iomazenil SPECT - 1H-MRS - 22q11.2 deletion syndrome - agyria - brain malformation - epilepsy - polymicrogyria
 

  • References

  • 1 Botto LD, May K, Fernhoff PM et al. A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics 2003; 112: 101-107
    CrossrefPubMedGoogle Scholar
  • 2 Choi CG, Frahm J. Localized proton MRS of the human hippocampus: metabolite concentrations and relaxation times. Magn Reson Med 1999; 41: 204-207
    CrossrefPubMedGoogle Scholar
  • 3 Cramer SC, Schaefer PW, Krishnamoorthy KS. Microgyria in the distribution of the middle cerebral artery in a patient with DiGeorge syndrome. J Child Neurol 1996; 11: 494-497
    CrossrefPubMedGoogle Scholar
  • 4 Gerkes EH, Hordijk R, Dijkhuizen T et al. Bilateral polymicrogyria as the indicative feature in a child with a 22q11.2 deletion. Eur J Med Genet 2010; 53: 344-346
    CrossrefPubMedGoogle Scholar
  • 5 Harada M, Miyoshi H, Uno M et al. Neuronal impairment of adult moyamoya disease detected by quantified proton MRS and comparison with cerebral perfusion by SPECT with Tc-99 m HM-PAO: a trial of clinical quantification of metabolites. J Magn Reson Imaging 1999; 10: 124-129
    CrossrefPubMedGoogle Scholar
  • 6 Harding B, Copp AJ. Malformations. In: Graham DI, Lantos PL. editors. Greenfield’s Neuropathology. 6th edn. London: Arnold; 1997: 397-533
    Google Scholar
  • 7 Hauser WA. Epidemiology of epilepsy in children. In: Pellock JM, Dodson WE, Bourgeois B. editors. Pediatric epilepsy diagnosis and therapy. New York: Demos Medical Publishing, Inc.; 2001: 81-96
    Google Scholar
  • 8 Hirose S, Okada M, Kaneko S et al. Are some idiopathic epilepsies disorders of ion channels? A working hypothesis. Epilepsy Res 2000; 41: 191-204
    CrossrefPubMedGoogle Scholar
  • 9 Jecobs K, Kharazia V, Prince D. Mechanisms underlying epileptogenesis in cortical malformation. Epilepsy Res 1999; 36: 165-188
    CrossrefPubMedGoogle Scholar
  • 10 Kaminaga T, Kobayashi M, Abe T. Proton magnetic resonance spectroscopy in disturbances of cortical development. Neuroradiology 2001; 43: 575-580
    CrossrefPubMedGoogle Scholar
  • 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 A 2004; 129: 29-34
    PubMedGoogle Scholar
  • 12 Kawame H, Kurosawa K, Akatsuka A et al. Polymicrogyria is an uncommon manifestation in 22q11.2 deletion syndrome. Am J Med Genet 2000; 94: 77-78
    CrossrefPubMedGoogle Scholar
  • 13 Kobrynski LJ, Sullivan KE. Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet 2007; 370: 1443-1452
    CrossrefPubMedGoogle Scholar
  • 14 Kuzniecky R, Hetherington H, Pan J et al. Proton spectroscopic imaging at 4.1 tesla in patients with malformations of cortical development and epilepsy. Neurology 1997; 48: 1018-1024
    CrossrefPubMedGoogle Scholar
  • 15 Li LM, Cendes F, Bastos AC et al. Neuronal metabolic dysfunction in patients with cortical developmental malformations: a proton magnetic resonance spectroscopic imaging study. Neurology 1998; 50: 755-759
    CrossrefPubMedGoogle Scholar
  • 16 Lindsay EA, Vitelli F, Su H et al. Tbx1 haploinsufficiency in the DiGeorge syndrome region causes aortic arch defects in mice. Nature 2001; 410: 97-101
    CrossrefPubMedGoogle Scholar
  • 17 McDonald-McGinn DM, Tonnesen MK, Laufer-Cahana A et al. Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net!. Genet Med 2001; 3: 23-29
    CrossrefPubMedGoogle Scholar
  • 18 McDonald-McGinn DM, Kirschner R, Goldmuntz E et al. The Philadelphia story: the 22q11.2 deletion: report on 250 patients. Genet Couns 1999; 10: 11-24
    PubMedGoogle Scholar
  • 19 McDonald-McGinn DM, Gripp KW, Kirschner RE et al. Craniosynostosis: another feature of the 22q11.2 deletion syndrome. Am J Med Genet A 2005; 136: 358-362
    PubMedGoogle Scholar
  • 20 Mescher M, Tannus A, Johnson MO et al. Solvent suppression using selective echo dephasing. J Magn Reson Series A 1996; 123: 226-229
    CrossrefPubMedGoogle Scholar
  • 21 Mescher M, Merkle H, Kirsch J et al. Simultaneous in vivo spectral editing and water suppression. NMR Biomed 1998; 11: 266-272
    CrossrefPubMedGoogle Scholar
  • 22 Morimoto K, Tamagami H, Matsuda K. Central-type benzodiazepine receptors and epileptogenesis: basic mechanisms and clinical validity. Epilepsia 2005; 46 (Suppl. 05) 184-188
    CrossrefPubMedGoogle Scholar
  • 23 Öz G, Terpstra M, Tkáč I et al. Proton MRS of the unilateral substantia nigra in the human brain at 4 tesla: detection of high GABA concentrations. Magn Reson Med 2006; 55: 296-301
    CrossrefPubMedGoogle Scholar
  • 24 Marcorelles P, Laquerrière A, Adde-Michel C et al. Evidence for tangential migration disturbances in human lissencephaly resulting from a defect in LIS1, DCX and ARX genes. Acta Neuropathol 2010; 120: 503-515
    CrossrefPubMedGoogle Scholar
  • 25 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 A 2006; 140: 2416-2425
    PubMedGoogle Scholar
  • 26 Schaer M, Glaser B, Cuadra MB et al. Congenital heart disease affects local gyrification in 22q11.2 deletion syndrome. Dev Med Child Neurol 2009; 51: 746-753
    CrossrefPubMedGoogle Scholar
  • 27 Simister RJ, McLean MA, Barker GJ et al. Proton magnetic resonance spectroscopy of malformations of cortical development causing epilepsy. Epilepsy Res 2007; 74: 107-115
    CrossrefPubMedGoogle Scholar
  • 28 Sullivan KE, Jawad AF, Randall P et al. Lack of correlation between impaired T cell production, immunodeficiency, and other phenotypic features in chromosome 22q11.2 deletion syndromes (DiGeorge syndrome/velocardiofacial syndrome). Clin Immunol Immunopathol 1998; 86: 141-146
    CrossrefPubMedGoogle Scholar
  • 29 Terpstra M, Henry PG, Gruetter R. Measurement of reduced glutathione (GSH) in human brain using LCModel analysis of difference-edited spectra. Magn Reson Med 2003; 50: 19-23
    CrossrefPubMedGoogle Scholar
  • 30 Woermann FG, McLean MA, Bartlett PA et al. Quantitative short echo time proton magnetic resonance spectroscopic imaging study of malformations of cortical development causing epilepsy. Brain 2001; 124: 427-436
    CrossrefPubMedGoogle Scholar
  • 31 Yagi H, Furutani Y, Hamada H et al. Role of TBX1 in human del22q11.2 syndrome. Lancet 2003; 362: 1366-1373
    CrossrefPubMedGoogle Scholar
  • 32 Yamamoto T, Sameshima K, Sekido K et al. Trigonocephaly in a boy with paternally inherited deletion 22q11.2 syndrome. Am J Med Genet A 2006; 140: 1302-1304
    PubMedGoogle Scholar