Advertisement

Developmental instability of the cerebellum and its relevance to Down syndrome

  • B. L. Shapiro
Chapter

Summary

It has been recognized for many years that cerebellar abnormalities are frequently observed in association with Down syndrome (DS). An important question to be asked about these and other findings in DS is whether their occurrence (i) is attributable to specific loci on the triplicated chromosome or chromosomal segment or (ii) derives from exaggerated responses secondary to the genetic imbalance resulting from trisomy (Ts). Recently, similar cerebellar alterations were observed in subjects with DS and in Ts65Dn mice (Baxter et al., 2000), mice segmentally trisomic for a portion of chromosome 16, which is homologous for loci on the long arm of human chromosome 21. It was concluded by these authors that the occurrence of similar cerebellar changes in DS and in the DS mouse model resulted from triplication of these homologous loci in the two trisomic organisms, i.e. cerebellar development is affected similarly by homologous loci in each species. They wrote that their study of Ts65Dn mice “correctly predicts an analagous pathology in humans” ... and that... “The candidate region of genes on chromosome 21 affecting cerebellar development in DS is therefore delimited to the subset of genes whose orthologs are at dosage imbalance in Ts65Dn mice, providing the first localization of genes affecting a neuroanatomical phenotype in DS.” Findings described in this review suggest otherwise — that cerebellar findings in DS and in the Ts65Dn mouse are a result of exaggerated vulnerability in general of the cerebellum to disturbing events and that liability to expression of response(s) is exacerbated by trisomy. This conclusion is based on the following: (i) the cerebellum has an extended postnatal development; (ii) numerous genetic, environmental, epigenetic and metabolic conditions express cerebellar changes similar to those observed in Down syndrome; (iii) most if not all chromosomal imbalance syndromes express similar cerebellar abnormalities; (iv) the cerebellum is particularly sensitive to diverse toxic agents which may act prenatally, postnatally and/or in the mature organism; and (v) cerebellar abnormalities similar to those found in Ts65Dn mice have been described in Tsl9 mice which have no segments homologous to any segment of human chromosome 21. An unavoidable conclusion from the review is that triplication of specific loci on 21q is an unlikely explanation for the cerebellar findings in DS. A simple positive control, in which the effect of triplication of loci other than those in question on a specific phenotype, should be used in experiments comparing human and experimental trisomies. As pointed out many years ago by Lorke and his coworkers (Lorke et al., 1989; Lorke, 1994; Lorke and Albrecht, 1994) similar phenotypic findings in the presence of different trisomies in the same species would suggest that the trisomic state itself rather than the gene content of a particular trisomy is responsible for the genesis of traits at issue.

Keywords

Purkinje Cell Granule Cell Down Syndrome Docoshexaenoic Acid Cerebellar Volume 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alashari M, Chen M, Poskanzer L (1995) Partial deletion of chromosome 6p - autopsy findings in a premature infant and review of the literature. Pediatr Pathol & Lab Med 15: 941–947CrossRefGoogle Scholar
  2. Arts WFM, Hofstee Y, Drejer GF, Beverstodk GC, Oosterwijk JC (1995) Cerebellar and brainstem hypoplasia in a child with partial trisomy for the short arm of chromosome 5 and partial trisomy for the short arm of chromosome 10. Neuropediatrics 26: 41– 44PubMedCrossRefGoogle Scholar
  3. Aylward EH, Habbak R, Warren AC, Pulsifer MB, Barta PE, Jerram M, Pearlson GD (1997) Cerebellar volume in adults with Down syndrome. Arch Neurol 54: 209–212PubMedCrossRefGoogle Scholar
  4. Baker KG, Harding AJ, Halliday GM, Kril jjarper CG (1999) Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke’s encephalopathy. Neurosci 91: 429–438CrossRefGoogle Scholar
  5. Barkovich AJ (1998) Neuroimaging manifestations and classification of congenital muscular dystrophies. Am J Neuroradiol 19: 1389–1396PubMedGoogle Scholar
  6. Bastion AJ, Mugnaini E, Thach WY (1999) “Cerebellum” in fundamental neuroscience. Academic Press, San Diego, pp 973–992Google Scholar
  7. Baxter LL, Moran TH, Richtsmeier JT, Troncoso J, Reeves RH (2000) Discovery and genetic localization of Down syndrome cerebellar phenotypes. Hum Mol Genet 9: 195–202PubMedCrossRefGoogle Scholar
  8. Chamberlain MP, Sturgess NC, Lock EA, Reed CJ (1999) Methyl iodide toxicity in rat cerebellar cells in vitro: the role of glutathione. Toxicology 139: 27–37PubMedCrossRefGoogle Scholar
  9. Chance PF, Cavalier L, Satran D, Pellegrino JE, Koenig M, Dobyns WB (1999) Clinical nosologic and genetic aspects of Joubert and related syndromes. J Child Neurol 14: 660–666PubMedCrossRefGoogle Scholar
  10. Ciesielski KT, Yanofsky R, Ludwig RN, Hill DE, Hart BL, Astur RS, Snyder T (1994) Hypoplasia of the cerebellar vermis and cognitive defects in survivors of childhood leukemia. Arch Neurol 51: 985PubMedCrossRefGoogle Scholar
  11. Conlee JW, Shapiro SM (1997) Development of cerebellar hypoplasia in jaundiced Gunn rats - a quantitative light microscoopic analysis. Acta Neuropathol 93: 450–460PubMedCrossRefGoogle Scholar
  12. Coyle JT, Oster-Granite ML, Gearhart JD (1986) The neurobiologic consequences of Down syndrome. Brain Res Bull 16: 773–787PubMedCrossRefGoogle Scholar
  13. Crome L (1965) The pathology of Down’s disease. In: Hilliard LT, Kirman BH (eds) Mental deficiency, 2nd ed. J & A Churchill Ltd, LondonGoogle Scholar
  14. Crome L, Cowie V, Slater E (1966) A statistical note on cerebellar and brain-stem weight in mmongolism. J Ment Def Res 10: 69–72Google Scholar
  15. Davidoff LM (1928) The brain in mongolian idiocy: a report of ten cases. Arch Neurol Psychiatr 20: 1229–1257CrossRefGoogle Scholar
  16. Davisson MT, Schmidt C, Reeves RH, Irving NG, Akeson EC, Harris BS, Bronson RT (1993) Segmental trisomy as a mouse model for Down syndrome. Prog Clin Biol Res 384: 117–133PubMedGoogle Scholar
  17. de Lonlay P, Cormier-Daire V, Vuillaumier-Barrot S, Cuer M, Durand G, Munnich A, Saudubray JM, Seta N (2000) “Carbohydrate-deficient glycoprotein” syndrome. Arch Pediatric 7: 173–184CrossRefGoogle Scholar
  18. Dembinski J, Heyl W, Steidel K, Hermanns B, Hörnchen H, Schröder W (1997) The Cantrell-sequence: a result of maternal exposure to aminopropionitriles? Am J Perinatal 14: 567–571CrossRefGoogle Scholar
  19. Desouza N, Chaudhuri R, Bingham J, Cox T (1994) MRI in cerebellar hypoplasia. Neuroradiology 36: 148–151PubMedCrossRefGoogle Scholar
  20. Desouza N, Chaudhuri R, Bingham J, Cox T (1994) MRI in cerebellar hypoplasia. Neuroradiol 36: 148–151CrossRefGoogle Scholar
  21. Dobbing J, Sands J (1973) Quantitative growth and development of human brain. Arch Dis Childhood 48: 757–767CrossRefGoogle Scholar
  22. Dollfus H, Joannyflinois O, Docofenzy M, Veyre L, Joannyflinois L, Khoury M, Jonveaux P, Abitbol M, Dufier JL (1998) Gillespie syndrome phenotype with a t(X-ll) (p22.32-p-12) de novo translocation. Am J Ophthalmol 125: 397–399PubMedCrossRefGoogle Scholar
  23. Down JLH (1866) Observation of an ethnic classification of idiots. London Hosp Clin Lect Rep 3: 259Google Scholar
  24. Eisenman LM, Brothers R, Tran MH, Kean RB, Dickson GM, Dietzschold B, Hooper DC (1999) Neonatal Borna disease virus infection in the rat causes a loss of Purkinje cells in the cerebellum. J Neurovirol 5: 181–189PubMedCrossRefGoogle Scholar
  25. Ferguson SA, Holson RR (1999) Neonatal dexamethasone on day 7 causes mild hyperactivity and cerebellar stunting. Neurotoxicol Teratol 21: 71–76PubMedCrossRefGoogle Scholar
  26. Ferguson SA, Paule MG, Holson RR (1996) Functional effects of methylozomethanol - induced cerebellar hypoplasia in rats. Neurotoxicol Teratol 18: 529–537PubMedCrossRefGoogle Scholar
  27. Ferrer I, Ribalta T, Fabregues I, Pineda M, Cusi V (1986) A Golgi study of cerebellar malformation in 13 trisomy. Clin Neuropathol 5: 53–59PubMedGoogle Scholar
  28. Fonnum F, Lock EA (2000) Cerebellum as a target for toxic substances. Toxicol Lett 112–113: 9–16PubMedCrossRefGoogle Scholar
  29. Freeman JH, Barone Jr H, Stanton ME (1995) Disruption of cerebellar maturation by an antimitotic agent impairs the ontogeny of eyeblink conditioning in rats. J Neurosci 15: 7301–7314PubMedGoogle Scholar
  30. Furuita H, Takeuchi T, Uematsu K (1998) Effects of eicosapentaenic and docoshexaenoic acids on growth, survival and brain development of larval Japanese flounder (paralichthysolivaceus). Aquaculture 161: 269–279CrossRefGoogle Scholar
  31. Gearhart JD, Davisson MT, Oster-Granite (1986) Autosomal aneuploidy in mice: generation and developmental consequences. Brain Res Bull 16: 789–801PubMedCrossRefGoogle Scholar
  32. Gropp A, Giers D, Kolbus U (1974) Trisomy in the fetal backcross progeny of male and female metacentric heterozygotes in the mouse. I. Cytogenet Cell Genet 13: 511–535CrossRefGoogle Scholar
  33. Gullotta F, Rehder H, Gropp A (1981) Descriptive neuropathology of chromosomal disorders in man. Hum Genet 57: 337–344PubMedCrossRefGoogle Scholar
  34. Heaton MB, Mitchell JJ, Paiva M (1999) Ethanol-induced alterations in neurotrophin expression in developing cerebellum: relationship to periods of temporal susceptibility. Alcoholism 23: 1637–1642PubMedGoogle Scholar
  35. Hekmatpanah J, Haghighat N, Adams CR (1994) Alcohol consumption by nursing rats and its effect on the cerebellum of offspring. Alcohol Alcoholism 29: 535 ffGoogle Scholar
  36. Hewickertrautwein M, Liess B, Trautwein G (1995) Brain lesions in calves following transplacental infection with bovine-virus diarrhoea virus. Zentralbl Veterinarmed - Reihe B 42: 65–77Google Scholar
  37. Hill LH, Rivello D, Peterson C, Marchese S (1991) The transverse cerebellar diameter in the second trimester is unaffected in Down syndrome. Am J Obstet Gynecol 164: 101–103PubMedGoogle Scholar
  38. Hjelde T, Mehl A, Schanke TM, Fonnum F (1998) Teratogenic effects of trichlorfon (metrifonate) on the guinae-pig-determination of the effective dose and the sensitive period. Neurochem Int 32: 469–477PubMedCrossRefGoogle Scholar
  39. Hornig M, Weisenböck - Horsscroft N, Lipkin I (1999) An infection-based model of neurodevelopmental damage. Proc Natl Acad Sci USA 96: 12102–12107PubMedCrossRefGoogle Scholar
  40. Ieshima A, Kisa T, Yoshino K, Takashima S, Takeshita K (1984) A morphometric CT study of Down’s syndrome showing small posterior fossa and calcification of basal ganglia. Neuroradiology 26: 493–498PubMedCrossRefGoogle Scholar
  41. Ingram JL, Peckham SM, Tisdale B, Rodier PM (2000) Prenatal exposure of rats to valproicacicreproducesthecerebellaranomaliesassociatedwithautism. Neurotoxicol Teratol 22: 319–324PubMedCrossRefGoogle Scholar
  42. Jernigan TL, Bellugi U (1990) Anolalous brain morphology on magnetic resonance images in Williams syndrome and Down syndrome. Arch Neurol 47: 529–533PubMedCrossRefGoogle Scholar
  43. Jernigan TL, Bellugi U, Sowell E, Doherty S, Hesselink JR (1993) Cerreral morphologic distinctions between Williams and Down syndromes. Arch Neurol 50: 186–191PubMedCrossRefGoogle Scholar
  44. Kitano Y, Yasuda N, Shimizu T, Ohzono H, Iwamoto T (1997) Teratogenicity of Aino virus in the chick embryo. Res Vet Sci 62: 195–198PubMedCrossRefGoogle Scholar
  45. Kitano Y, Ohzono H, Yasuda N, Shimizu T (1996) Hydranencephaly, cerebellar hypoplasia, and myopathy in chick embryos infected with aino virus. Veterinary Pathol 33:672–681CrossRefGoogle Scholar
  46. Kolb B, Pedersen B, Ballermann M, Gibb R, Whishaw IQ (1999) Embryonic and postnatal injections of bromodeoxyuridine produce age-dependent morphological and behavioral abnormalities. J Neurosci 19: 2337–2346PubMedGoogle Scholar
  47. Lincke CR, van den Bogert C, Nijtmans LGJ, Wanders RJA, Tamminga P, Barth PG (1996) Cerebellar hypoplasia in respiratory chain dysfunction. Neuropediat 27: 216–218CrossRefGoogle Scholar
  48. Lorke DE (1994) Developmental characteristics of trisomy 19 mice. Acta Anat 150:159–169PubMedCrossRefGoogle Scholar
  49. Lorke DE, Klimaschewski (1992) Postnatal development of the locus coeruleus in trisomy 19 mice: morphological and morphometric study. Brain Res Bull 28: 923–930PubMedCrossRefGoogle Scholar
  50. Lorke DE, Neidermauntel (1993) Foliation of the cerebellar vermis in trisomy 19 mice.Brain Res Bull 32: 215–222PubMedCrossRefGoogle Scholar
  51. Lorke DE, Albrecht H (1994) Altered postnatal development of the visual cortex in trisomy 19 mice. Brain Res Bull 34: 563–570PubMedCrossRefGoogle Scholar
  52. Lorke DE, Stan A, Lierse W (1989) Morphogenesis of the cerbellum of trisomy 19 mice.Biomed. Res [Suppl] 3: 385–396Google Scholar
  53. Maier SE, Chen W-J A, Miller JA, West JR (1997) Fetal alcohol exposure and temporal vulnerability - regional differences in alcohol-inducedmicroencephaly as a function of the timing of binge-like alcohol exposure during rat brain development. Alcoholism 21: 1418–1428PubMedGoogle Scholar
  54. Maier SE, Miller JA, Blackwell JM, West JR (1999) Fetal alcohol exposure and temporal vulnerability: regional differences in cell loss as a function of the timing of bingelike alcohol exposure during brain development. Alcohol Clin Exp Res 23: 726–734PubMedGoogle Scholar
  55. Mallard C, Loeliger M, Copolov D, Rees S (2000) Reduced number of neurons in the hippocampus and the cerebellum in the postnatal guinae-pig following intrauterine growth-restriction. Neurosci 100: 327–333CrossRefGoogle Scholar
  56. Maserati E, Verri A, Seghezzi L, Tupler R, Federico A, Tiepolo L, Maraschio P (1999)Cerebellar dysgenesis and mental retardation associated with a complex chromosome rearrangement. Ann Genet 420: 210–214Google Scholar
  57. Mehl A, Rolseth V, Gordon S, Bjoraas M, Seeberg E, Fonnum F (2000) Brain hypoplasia caused by exposure to trichlorfon and dichlorvos during development can be ascribed to DNA alkylation damage and inhibition of DNA alkyltransferase repair.Neurotoxicol 21: 165–173Google Scholar
  58. Miki T, Harris S, Wilce P, Takeuchi Y, Bedi KS (1999) The effect of timing of ethanol exposure during early postnatal life on total number of Purkinje cells in rat cerebellum. J Anat 194: 423–431PubMedCrossRefGoogle Scholar
  59. Miller MW (1996) Effect of early exposure to ethanol on the protein and DNA contents of specific brain regions in the rat. Brain Res 734: 286–294PubMedCrossRefGoogle Scholar
  60. Moore DB, Walker DW, Heaton MB (1999) Neonatal ethanol exposure alters bcl-2 family in mRNA levels in the rat cerebellar vermis. Alcoholism 23: 1251–1261PubMedGoogle Scholar
  61. Mwangi DK (1998) Effect of propylthiouracil induced hypothyroidism in developing rat cerebellum. Comparison of cerebellar parameters in five day old normal and treated rat pups. East African Med J 75: 602–608Google Scholar
  62. Nakamura Y, Hashimoto T, Sasaguri Y, Yamana K, Tanaka S, Morodomi T, Murakami T, Machara F, Nakshima T, Fukuda S, et al (1986) Brain anomalies found in 18 trisomy: CT scanning, morphologic and morphometric study. Clin Neuropathol 5:47–52PubMedGoogle Scholar
  63. Nicolás JM, Fernández-Sola J, Robert J, Antúnez E, Cofán M, Cardenal C, Sacanella E, Estruch R, Urbano-Márquez R (2000) High ethanol intake and malnutriton in alcoholic cerebellar shrinkage. Qjm-Monthly J Assoc Physicians 93: 449–456CrossRefGoogle Scholar
  64. Ohmori H, Ogura Y, Yasuda M, Nakamura S, Hatta T, Kawano K, Michikawa T, Yamashita K, Mikoshiba K (1999) Developmental neurotoxicity of phenytoin on granule cells and Purkinje cells in mouse cerebellum. J Neurochem 72: 1497–1506PubMedCrossRefGoogle Scholar
  65. Online Mendelian Inheritance in Man, OMIM (TM) (2000) McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD) World Wide Web URL: http://www.ncbi.nlm.nih.gov/omim/Google Scholar
  66. Patterson MC (1999) Screening for “prelysosomal disorders”: carbohydrate-deficient glycoprotein syndromes. Child Neurol [14 Suppl]: S16–S22Google Scholar
  67. Pierce DR, Williams DK, Light KE (1999) Purkinje cell vulnerability to developmental exposure in the rat cerebellum. Alcohol 23: 1650–1659Google Scholar
  68. Ramaekers VT, Heimann G, Reul J, Thron A, Jacken J (1997) Genetic disorders and cerebellar structural abnormalities in childhood. Brain 120: 1739–1751PubMedCrossRefGoogle Scholar
  69. Ray DE, Holton JL, Nolan CC, Cavanagh JB, Harpur ES (1998) Neurotoxic potential of gadodiamide after injection into the lateral cerebral ventricle of rats. Am J Neuroradiol 19: 1455–1462PubMedGoogle Scholar
  70. Raz N, Torres IJ, Briggs SD, Spencer WD, Thorton AE, Loken WJ, Gunning FM, Mcquain JD, Driesen NR, Acker JD (1995) Selective neuroanatomic abnormalities in Down’s syndrome and their cognitive correlates: evidence from MRI morphometry. Neurology 45: 356–366PubMedCrossRefGoogle Scholar
  71. Rees S, Breen S, Loeliger M, Mccrabb G, Harding R (1999) Hypoxemia near mid-gestation has long-term effects on fetal brain development. J Neuropathol Exp Neurol 58: 932–945PubMedCrossRefGoogle Scholar
  72. Rice D, Barone S (2000) Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 108 [Suppl 3]: 511–533PubMedCrossRefGoogle Scholar
  73. Rintala J, Jaatinen P, Lu W, Sarviharjum M, Eriksson CJP, Laippala P, Kiianmaak K, Hervonen A (1997) Effects of lifelong ethanol consumption on cerebellar layer volumes in AA and ANA rats. Alcohol Clin Exp Res 21: 311–317PubMedCrossRefGoogle Scholar
  74. Roebuck TM, Mattson SN, Riley EP (1998) A review of the neuroanatomical findings in children with fetal alcohol syndrome or prenatal exposure to alcohol. Alcohol Clin Exp Res 22: 339–344PubMedCrossRefGoogle Scholar
  75. Rorke LB, Fogelson MH, Riggs HE (1968) Cerebellar heterotopia in infancy. Dev Med Child Neurol 10: 644–650PubMedCrossRefGoogle Scholar
  76. Rosati P, Guariglia L (1999) Cerebellar hypoplasia: could it be a sonogrphic finding of abnormal fetal karyotype in early pregnancy? Fetal Diagnosis Ther 14: 365–367CrossRefGoogle Scholar
  77. Rotmensch S, Goldstein I, Liberati M, Shalev J, Ben-Rafael Z, Copel JA (1997) Fetal transcerebellar diameter in Down syndrome. Obstet Gynecol 89: 534–537PubMedCrossRefGoogle Scholar
  78. Rubin SA, Bautista JR, Moran TH, Schwart GJ, Carbone KM (1999) Viral teratogenesis: brain developmental damage associated with maturation state at time of infection. Brain Res Dev Brain Res 112: 237–244PubMedCrossRefGoogle Scholar
  79. Schmidt-Sidor B, Wisniewski KE, Shepard TH, Sersen EA (1990) Brain growth in Down syndrome subjects 15 to 22 weeks of gestational age and birth to 60 months. Clin Neuropathol 9: 181–190PubMedGoogle Scholar
  80. Schnizel A (ed) (1984) Catalogue of unbalanced chromosome aberrations in man. Walter de Gruyter, Berlin New YorkGoogle Scholar
  81. Shapiro BL (1983) Down syndrome - a disruption of homeostasis. J Med Genet 14:241–269CrossRefGoogle Scholar
  82. Shapiro BL (1989) The pathogenesis of aneuploid phenotypes: the fallacy of explanatory reductionism. Am J Med Genet 33: 146–150PubMedCrossRefGoogle Scholar
  83. Shapiro BL (1992) Development of human autosomal aneuploid phenotypes (with an emphasis on Down syndrome). Acta Zool Fenn 191: 97–105Google Scholar
  84. Shapiro BL (1994) The environmental basis of he Down syndrome. Dev Med Child Neurol 36: 84–90PubMedCrossRefGoogle Scholar
  85. Shapiro BL (1999) The Down syndrome critical region. J Neural Transm [Suppl] 57: 41–60Google Scholar
  86. Sharp NJ, Davis BJ,Guy JS,Cullen JM,Steingold SF,Kornegay JN(1999) Hydranencephaly and cerebellar hypoplasia in two kittens attributed to intrauterine parvovirus infection. J Comp Pathol 121(1): 39–53PubMedCrossRefGoogle Scholar
  87. Shear PK, Sullivan EV, Lane B, Pfefferbaum A (1996) Mamillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia. Alcohol Clin Exp Res 20: 1489–1495PubMedCrossRefGoogle Scholar
  88. Simpson MG, Wyatt I, Jones HB, Gyte HJ, Widdowsson ES, Lock EA (1996) Neuro- pathological changes in rat brains following oral administration of 2-chloroproprionic acid. Neurotoxicol 17: 471–480Google Scholar
  89. Sørensen FW, Larsen JO, Eide R, Schionning JD (2000) Neuron loss in cerebellar cortex of rats exposed to mercry vapor: a stereological study. Acta Neuropathol 100: 95–100PubMedCrossRefGoogle Scholar
  90. Steinlin M (1998) Non-progressive congenital ataxias. Brain Dev 20: 199–208PubMedCrossRefGoogle Scholar
  91. Steinlin MI, Nadal D, Eich GF, Martin E, Boltshauser EJ (1996) Late intrauterine cytomegalovirus infection - clinical and neuroimaging findings. Pediat Neurol 15: 249–253PubMedCrossRefGoogle Scholar
  92. Steinlin M, Blaser S, Boltshauser E (1998) Cerebellar involvement in metabolic disorders - a pattern-recognition approach. Neuroradiology 40: 347–354PubMedCrossRefGoogle Scholar
  93. Steinlin M, Blaser S, Boltshauser E (1998) Cerebellar involvementin metaboloic disorders - a pattern-recognition approach [Article]. Neuroradiology 40: 347–354PubMedCrossRefGoogle Scholar
  94. Tamaraz JC, Rethoré M-O, Iba-Zizen M-T, Lejeune J, Cabanis EA (1987) Contribution of magnetic resonance imaging to the knowledge of CNS malformations related to chromosomal aberrations. Hum Genet 76: 265–273Google Scholar
  95. Thurmond AS, Nelson DW, Lowensohn RI, Young WP, Davis L (1989) Enlarged cis-terna magna in trisomy 18: prenatal ultrasonic diagnosis. Am J Obst Gynecol 161: 83–85Google Scholar
  96. Vekamans M, Trasler T (1986) Liability to cleft palate in trisomy 19 mouse embryos. J Craniofac Genet Dev [Suppl 2]: 235–240Google Scholar
  97. Wax JR, Benn P, Steinfeld JD, Ingardia CJ (2000) Prenatally diagnosed sacrococcygeal teratoma: a unique expression of trisomy lq. Cancer Genet Cytogenet 117: 84–86PubMedCrossRefGoogle Scholar
  98. Weis S (1991) Morphometry and magnetic resonance imaging of the human brain in normal controls and Down’s syndrome. Anat Rec 231: 593–598PubMedCrossRefGoogle Scholar
  99. Weis S, Weber G, Neuhold A, Rett A (1991) Down syndrome: MR quantification of brain structures and comparison with normal control subjects. AJNR 12: 1207–1211PubMedGoogle Scholar
  100. Williams RE, Jones P, Lock EA, Bachelard HS (1999) Biochemical and neurotoxilogical effects of L-2-chloropropionic acid on rodent brain. J Neurochem 73: 362–371PubMedCrossRefGoogle Scholar
  101. Wiltshire T, Pletcher M, Cole SE, Villanueva M, Birren B, Lehozcky J, Dewar K, Reeves RH (1999) Perfect conserved linkage across the entire mouse chromosome 10 region homologous to human chromosome 21. Genome Res 9: 1214–1222PubMedCrossRefGoogle Scholar
  102. Winter TC, Ostrovsky AA, Komaniski CA, Uhrich SB (2000) Cerebellar and frontal lobe hypoplasia in fetuses with trisomy 21: usefulness as combined US markers. Radiology 214: 533–538PubMedGoogle Scholar
  103. Xia JM, Simonyi A, Sun GY (1999) Chronic ethanol and iron administration on iron content, neuronal nitric oxide synthase, and superoxide dismutase in rat cerebellum. Alcohol Clin Exp Res 23: 702–707PubMedCrossRefGoogle Scholar
  104. Yamaguchi R, Naitoh Y, Uchida K, Hirano N, Wada Tateyama S (1996) Encephalopathy in suckling mice infected with Kasba (Chuzan) virus. J Comp Pathol 120: 347–256Google Scholar
  105. Ye P, Xing YZ, Dai ZH, Dercole AJ (1996) In vivo actions of insulin-like growth factor-1 (IGF-1) on cerebellum development in transgenic mice - evidence that IGF-1 increases proliferation of granule cell progenitors. Brain Res Dev Brain Res 95: 44–54PubMedCrossRefGoogle Scholar
  106. Zellweger H (1977) Down syndrome. In: Vinken PJ, Bruyn GW, Myrianthopoulos NC (eds) Handbook of clinical neurology: congenital malformations of the brain and skull, v 31, ch 10. Elsevier, Amsterdam, pp 367–469Google Scholar
  107. Zlotogora J (1992) Relation between the prevalence of anorectal malformations in children with Down syndrome and their prevalence in the general population. Am J Med Genet 44: 850CrossRefGoogle Scholar
  108. Zlotogora J, Abu-Dalu K, Lernan O, Sagi M, Voss R, Cohen T (1989) Anorectal malformations and Down syndrome. Am J Med Genet 34: 330–331PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 2001

Authors and Affiliations

  • B. L. Shapiro
    • 1
  1. 1.Departments of Oral Science and Laboratory Medicine and Pathology and Institute of Human GeneticsUniversity of MinnesotaMinneapolisUSA

Personalised recommendations