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Abstract

Advances in molecular genetics and radiological imaging technologies have increased the field of study of the cerebellum and its malformations. Correct diagnosis of cerebellar malformations is important in order to inform the patient’s family of the prognosis, recurrent risks, as well as genetic counseling. Integrated classification of malformations based on morphology, embryology, and molecular neurogenetics is recommended for achieving a correct diagnosis. This chapter reviews cerebellar malformations based on imaging findings, recent advances in embryology, and molecular neurogenetics.

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References

  • Acosta FL Jr, Binder DK, Barkovich AJ et al (2005) Neurocutaneous melanosis presenting with hydrocephalus case report and review of the literature. J Neurosurg 102:96–100

    PubMed  Google Scholar 

  • Aicardi J (2005) Aicardi syndrome. Brain Dev 27:164–171

    Article  PubMed  Google Scholar 

  • Aldinger KA, Lehmann OJ, Hudgins L et al (2009) FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation. Nat Genet 41:1037–1042

    Article  PubMed  CAS  Google Scholar 

  • Barkovich AJ (1998) Neuroimaging manifestations and classification of congenital muscular dystrophies. AJNR Am J Neuroradiol 19:1389–1396

    PubMed  CAS  Google Scholar 

  • Barkovich AJ (2005) Congenital malformations of the brain and skull. In: Barkovich AJ (ed) Pediatric neuroimaging, 4th edn. Lippincott Williams Wilkins, Philadelphia

    Google Scholar 

  • Barkovich AJ, Lindan CE (1994) Congenital cytomegalovirus infection of the brain: imaging analysis and embryologic considerations. AJNR Am J Neuroradiol 15:703–715

    PubMed  CAS  Google Scholar 

  • Barkovich AJ, Millen KJ, Dobyns WB (2007) A developmental classification of malformations of the brainstem. Ann Neurol 62:625–639

    Article  PubMed  Google Scholar 

  • Barkovich AJ, Millen KJ, Dobyns WB (2009) A developmental and genetic classification for midbrain-hindbrain malformations. Brain 132:3199–3230

    Article  PubMed  Google Scholar 

  • Barth PG (1993) Pontocerebellar hypoplasias. An overview of a group of inherited neurodegenerative disorders with fetal onset. Brain Dev 15:411–422

    Article  PubMed  CAS  Google Scholar 

  • Barth PG, Blennow G, Lenard HG et al (1995) The syndrome of autosomal recessive pontocerebellar hypoplasia, microcephaly, and extrapyramidal dyskinesia (pontocerebellar hypoplasia type 2): compiled data from 10 pedigrees. Neurology 45:311–317

    Article  PubMed  CAS  Google Scholar 

  • Berker M, Oruckaptan HH, Oge HK et al (2000) Neurocutaneous melanosis associated with Dandy-Walker malformation. Case report and review of the literature. Pediatr Neurosurg 33:270–273

    Article  PubMed  CAS  Google Scholar 

  • Boddaert N, Klein O, Ferguson N et al (2003) Intellectual prognosis of the Dandy-Walker malformation in children: the importance of vermian lobulation. Neuroradiology 45:320–324

    PubMed  CAS  Google Scholar 

  • Chaves-Vischer V, Pizzolato GP, Hanquinet S et al (2000) Early fatal pontocerebellar hypoplasia in premature twin sisters. Eur J Paediatr Neurol 4:171–176

    Article  PubMed  CAS  Google Scholar 

  • Chemli J, Abroug M, Tlili K et al (2007) Rhombencephalosynapsis diagnosed in childhood: clinical and MRI findings. Eur J Paediatr Neurol 11:35–38

    Article  PubMed  Google Scholar 

  • Chizhikov V, Millen KJ (2003) Development and malformations of the cerebellum in mice. Mol Genet Metab 80:54–65

    Article  PubMed  CAS  Google Scholar 

  • Chizhikov VV, Lindgren AG, Currle DS et al (2006) The roof plate regulates cerebellar cell-type specification and proliferation. Development 133:2793–2804

    Article  PubMed  CAS  Google Scholar 

  • Clement E, Mercuri E, Godfrey C et al (2008) Brain involvement in muscular dystrophies with defective dystroglycan glycosylation. Ann Neurol 64:573–582

    Article  PubMed  CAS  Google Scholar 

  • Demaerel P (2002) Abnormalities of cerebellar foliation and fissuration: classification, neurogenetics and clinicoradiological correlations. Neuroradiology 44:639–646

    Article  PubMed  CAS  Google Scholar 

  • Demaerel P, Morel C, Lagae L et al (2004) Partial rhombencephalosynapsis. AJNR Am J Neuroradiol 25:29–31

    PubMed  Google Scholar 

  • Donkelaar HJ, Wesseling P, Lammens M et al (2003) Development and the developmental disorders of human brain. J Neurol 250:1025–1036

    Article  PubMed  Google Scholar 

  • Fink AJ, Englund C, Daza RA et al (2006) Development of the deep cerebellar nuclei: transcription factors and cell migration from the rhombic lip. J Neurosci 26:3066–3076

    Article  PubMed  CAS  Google Scholar 

  • Fukuyama Y, Osawa M, Suzuki H (1981) Congenital progressive muscular dystrophy of the Fukuyama type-clinical, genetic, and pathological considerations. Brain Dev 3:1–29

    Article  PubMed  CAS  Google Scholar 

  • Goldowitz D, Hamre K (1998) The cells and molecules that make a cerebellum. Trends Neurosci 21:375–382

    Article  PubMed  CAS  Google Scholar 

  • Hart MN, Malamud N, Ellis WG (1972) The Dandy-Walker syndrome. A clinicopathological study based on 28 cases. Neurology 22:771–780

    Article  PubMed  CAS  Google Scholar 

  • Hong SE, Shugart YY, Huang DT et al (2000) Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations. Nat Genet 26:93–96

    Article  PubMed  CAS  Google Scholar 

  • Jaspan T (2008) New concepts on posterior fossa malformations. Pediatr Radiol 38:409–414

    Article  Google Scholar 

  • Johnson VP, Swayze VW II, Sato Y et al (1996) Fetal alcohol syndrome: craniofacial and central nervous system manifestations. Am J Med Genet 61:329–339

    Article  PubMed  CAS  Google Scholar 

  • Klisch J, Juengling F, Spreer J et al (2001) Lhermitte-Duclos disease: assessment with MR imaging, positron emission tomography, single-photon emission CT, and MR spectroscopy. AJNR Am J Neuroradiol 22:824–830

    PubMed  CAS  Google Scholar 

  • Louie CM, Gleeson JG (2005) Genetic basis of Joubert syndrome and related disorders of cerebellar development. Hum Mol Genet 14:235–242

    Article  Google Scholar 

  • Lumsden A, Krumlauf R (1996) Patterning the vertebrate neuraxis. Science 274:1009–1115

    Article  Google Scholar 

  • Mallow DW, Herrick MK, Gathman G (1980) Fetal exposure to anticonvulsant drugs. Detailed pathological study of a case. Arch Pathol Lab Med 104:215–218

    PubMed  CAS  Google Scholar 

  • Mercuri E, Topaloglu H, Brockington M et al (2006) Spectrum of brain changes in patients with congenital muscular dystrophy and FKRP gene mutations. Arch Neurol 63:251–257

    Article  PubMed  Google Scholar 

  • Messerschmidt A, Brugger PC, Boltshauser E et al (2005) Disruption of cerebellar development: potential complication of extreme prematurity. AJNR Am J Neuroradiol 26:1659–1667

    PubMed  Google Scholar 

  • Metry DW, Dowd CF, Barkovich AJ et al (2001) The many faces of PHACE syndrome. J Pediatr 139:117–123

    Article  PubMed  CAS  Google Scholar 

  • Muntoni F, Brockington M, Blake DJ et al (2002) Defective glycosylation in muscular dystrophy. Lancet 360:1419–1421

    Article  PubMed  Google Scholar 

  • Nakamura H, Watanabe Y (2005) Isthmus organizer and regionalization of the mesencephalon and metencephalon. Int J Dev Biol 49:231–235

    Article  PubMed  CAS  Google Scholar 

  • Nelson MD Jr, Maher K, Gilles FH (2004) A different approach to cysts of the posterior fossa. Pediatr Radiol 34:720–732

    Article  PubMed  Google Scholar 

  • Norman RM (1966) Neuropathological findings in trisomies 13–15 and 17–18 with special reference to the cerebellum. Dev Med Child Neurol 8:170–177

    Article  PubMed  CAS  Google Scholar 

  • O’Rahilly R, Müller F (1996) Human embryology and teratology. Wiley-Liss, New York

    Google Scholar 

  • Parisi MA, Dobyns WB (2003) Human malformations of the midbrain and hindbrain: review and proposed classification scheme. Mol Genet Metab 80:36–53

    Article  PubMed  CAS  Google Scholar 

  • Pascual-Castroviejo I, Velez A, Pascual-Pascual SI et al (1991) Dandy-Walker malformation: analysis of 38 cases. Childs Nerv Syst 7:88–97

    PubMed  CAS  Google Scholar 

  • Patel S, Barkovich AJ (2002) Analysis and classification of cerebellar malformations. AJNR Am J Neuroradiol 23:1074–1087

    PubMed  Google Scholar 

  • Patel MS, Becker LE, Toi A et al (2006) Severe, fetal-onset form of olivopontocerebellar hypoplasia in three sibs: PCH type 5? Am J Med Genet A 140:594–603

    PubMed  Google Scholar 

  • Poretti A, Boltshauser E, Loenneker T et al (2007) Diffusion tensor imaging in Joubert syndrome. AJNR Am J Neuroradiol 28:1929–1933

    Article  PubMed  CAS  Google Scholar 

  • Poretti A, Prayer D, Boltshauser E (2009) Morphological spectrum of prenatal cerebellar disruptions. Eur J Paediatr Neurol 13:397–407

    Article  PubMed  Google Scholar 

  • Poretti A, Limperopoulos C, Roulet-Perez E et al (2010) Outcome of severe unilateral cerebellar hypoplasia. Dev Med Child Neurol 52:718–724

    Article  PubMed  Google Scholar 

  • Quisling RG, Barkovich AJ, Maria BL (1999) Magnetic resonance imaging features and classification of central nervous system malformations in Joubert syndrome. J Child Neurol 14:628–635

    Article  PubMed  CAS  Google Scholar 

  • Rajab A, Mochida GH, Hill A et al (2003) A novel form of pontocerebellar hypoplasia maps to chromosome 7q11-21. Neurology 60:1664–1667

    Article  PubMed  CAS  Google Scholar 

  • Ramaekers VT, Heimann G, Reul J et al (1997) Genetic disorders and cerebellar structural abnormalities in childhood. Brain 120:1739–1751

    Article  PubMed  Google Scholar 

  • Rengachary SS, Watanabe I (1981) Ultrastructure and pathogenesis of intracranial arachnoid cysts. J Neuropathol Exp Neurol 40:61–83

    PubMed  CAS  Google Scholar 

  • Sarnat HB (2000) Molecular genetics classification of central nervous system malformations. J Child Neurol 15:675–687

    Article  PubMed  CAS  Google Scholar 

  • Sarnat HB, Flores-Sarnat L (2003) Etiological classification of CNS malformations: integration of molecular genetics and morphological criteria. Epileptic Disord 5:35–43

    Google Scholar 

  • Sarnat HB, Menkes JH (2000) How to construct a neural tube. J Child Neurol 15:110–124

    Article  PubMed  CAS  Google Scholar 

  • Sellick GS, Barker KT, Stolte-Dijkstra I et al (2004) Mutations in PTF1A cause pancreatic and cerebellar agenesis. Nat Genet 36:1301–1305

    Article  PubMed  CAS  Google Scholar 

  • Sidman RL, Rakic P (1982) Development of the human central nervous system. In: Haymaker W, Adams RD (eds) Histology and histopathology of the nervous system. Charles C. Thomas, Springfield

    Google Scholar 

  • Siebert JR (2006) A pathological approach to anomalies of the posterior fossa. Birth Defects Res A Clin Mol Teratol 76:674–684

    Article  PubMed  CAS  Google Scholar 

  • Soto-Ares G, Delmaire C, Deries B et al (2000) Cerebellar cortical dysplasia: MR findings in a complex entity. AJNR Am J Neuroradiol 21:1511–1519

    PubMed  CAS  Google Scholar 

  • Soto-Ares G, Devisme L, Jorriot S et al (2002) Neuropathologic and MR imaging correlation in a neonatal case of cerebellar cortical dysplasia. AJNR Am J Neuroradiol 23:1101–1104

    PubMed  Google Scholar 

  • Soto-Ares G, Joyes B, Lemaitre MP et al (2003) MRI in children with mental retardation. Pediatr Radiol 33:334–345

    PubMed  Google Scholar 

  • Sukhudyan B, Jaladyan V, Melikyan G et al (2010) Gómez-López-Hernández syndrome: reappraisal of the diagnostic criteria. Eur J Pediatr 169:1523–1528

    Article  PubMed  Google Scholar 

  • Sztriha L, Johansen JG (2005) Spectrum of malformations of the hindbrain (cerebellum, pons, and medulla) in a cohort of children with high rate of parental consanguinity. Am J Med Genet A 135:134–141

    PubMed  Google Scholar 

  • Toelle SP, Yalcinkaya C, Kocer N et al (2002) Rhombencephalosynapsis: clinical findings and neuroimaging in 9 children. Neuropediatrics 33:209–214

    Article  PubMed  CAS  Google Scholar 

  • Utsunomiya H, Takano K, Ogasawara T et al (1998) Rhombencephalosynapsis: cerebellar embryogenesis. AJNR Am J Neuroradiol 19:547–549

    PubMed  CAS  Google Scholar 

  • Valente EM, Silhavy JL, Brancati F et al (2006) Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome. Nat Genet 38:623–625

    Article  PubMed  CAS  Google Scholar 

  • Wang VY, Zoghbi HY (2001) Genetic regulation of cerebellar development. Nat Rev Neurosci 2:484–491

    Article  PubMed  CAS  Google Scholar 

  • Wassmer E, Davies P, Whitehouse WP et al (2003) Clinical spectrum associated with cerebellar hypoplasia. Pediatr Neurol 28:347–351

    Article  PubMed  Google Scholar 

  • Yamada M, Terao M, Terashima T et al (2007) Origin of climbing fiber neurons and their developmental dependence on Ptf1a. J Neurosci 27:10924–10934

    Article  PubMed  CAS  Google Scholar 

  • Zafeiriou DI, Vargiami E, Boltshauser E (2004) Cerebellar agenesis and diabetes insipidus. Neuropediatrics 35:364–367

    Article  PubMed  CAS  Google Scholar 

  • Zaki MS, Abdel-Aleem A, Abdel-Salam G et al (2008) The molar tooth sign: a new Joubert syndrome and related cerebellar disorders classification system tested in Egyptian families. Neurology 12:556–565

    Article  Google Scholar 

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Correspondence to Ozlem Alkan MD .

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Alkan, O., Kizilkilic, O., Yildirim, T. (2013). Cerebellar Malformations. In: Manto, M., Schmahmann, J.D., Rossi, F., Gruol, D.L., Koibuchi, N. (eds) Handbook of the Cerebellum and Cerebellar Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1333-8_82

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