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01-09-2009

Malformations of the Midbrain and Hindbrain: A Retrospective Study and Review of the Literature

Authors: Ozlem Alkan, Osman Kizilkilic, Tulin Yildirim

Published in: The Cerebellum | Issue 3/2009

Abstract

We report the results of a retrospective analysis of radiological and clinical findings in 45 cases of midbrain–hindbrain anomalies and review recent advances in embryology and molecular neurogenetics. Among 45 patients with midbrain–hindbrain malformations, 16 cases of molar tooth malformation, 12 of cerebellar hypoplasia, ten of posterior fossa cyst and cerebellar vermian hypoplasia, three of rhombencephalosynapsis, two of Fukuyama congenital muscular dystrophy and two cases of isolated cerebellar dysplasia were identified. Twenty-six patients presented with motor-mental retardation, which was the most common clinical finding. Eleven patients were born to consanguineous parents. The correct diagnosis of cerebellar malformation is important for determining prognosis, the risk of recurrence and the need for genetic counselling. Integrated classification of malformations based on morphology, embryology and molecular neurogenetics may be useful.

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

Soto-Ares G, Joyes B, Lemaitre MP, Vallee L, Pruvo JP (2003) MRI in children with mental retardation. Pediatr Radiol 33:334–345PubMed

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

Sarnat HB, Flores-Sarnat L (2003) Etiological classification of CNS malformations: integration of molecular genetics and morphological criteria. Epileptic Disord 5(Suppl 2):S35–S43PubMed

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

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

Millen KJ, Millonig JH, Wingate RJ, Alder J, Hatten ME (1999) Neurogenetics of the cerebellar system. J Child Neurol 14:574–581PubMedCrossRef

Hallonet ME, Teillet MA, Le Douarin NM (1990) A new approach to the development of the cerebellum provided by the quail-chick marker system. Development 108:19–31PubMed

Hallonet ME, Le Douarin NM (1993) Tracing neuroepithelial cells of the mesencephalic and metencephalic alar plates during cerebellar ontogeny in quail-chick chimaeras. Eur J Neurosci 5:1145–1155PubMedCrossRef

10.

Joyner AL (1996) Engrailed, Wnt and Pax genes regulate midbrain–hindbrain development. Trends Genet 12:15–20PubMedCrossRef

11.

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

12.

Barkovich AJ, Millen KJ, Dobyns WBA (2007) Developmental classification of malformations of the brainstem. Ann Neurol 62:625–639PubMedCrossRef

13.

Demaerel P, Morel C, Lagae L, Wilms G (2004) Partial rhombencephalosynapsis. AJNR Am J Neuroradiol 25:29–31PubMed

14.

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

15.

Utsunomiya H, Takano K, Ogasawara T, Hashimoto T, Fukushima T, Okazaki M (1998) Rhombencephalosynapsis: cerebellar embryogenesis. AJNR Am J Neuroradiol 19:547–549PubMed

16.

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. Thomas, Springfield, III, pp 3–145

17.

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

18.

Nagai T, Aruga J, Takada S, Gunther T, Sporle R, Schughart K, Mikoshiba K (1997) The expression of the mouse Zic1, Zic2, and Zic3 gene suggests an essential role for Zic genes in body pattern formation. Dev Biol 182:299–313PubMedCrossRef

19.

Muntoni F, Brockington M, Blake DJ, Torelli S, Brown SC (2002) Defective glycosylation in muscular dystrophy. Lancet 360:1419–1421PubMedCrossRef

20.

Toda T, Segawa M, Nomura Y et al (1993) Localization of a gene for Fukuyama type congenital muscular dystrophy to chromosome 9q31–33. Nat Genet 5:283–286PubMedCrossRef

21.

Kobayashi K, Nakahori Y, Miyake M et al (1998) An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy. Nature 394:388–392PubMedCrossRef

22.

Beltran-Valero de Bernabe D, Currier S, Steinbrecher A et al (2002) Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker–Warburg syndrome. Am J Hum Genet 71:1033–1043PubMedCrossRef

23.

Cormand B, Avela K, Pihko H et al (1999) Assignment of the muscle–eye–brain disease gene to 1p32–p34 by linkage analysis and homozygosity mapping. Am J Hum Genet 64:126–135PubMedCrossRef

24.

Joubert M, Eisenring JJ, Robb JP, Andermann F (1969) Familial agenesis of the cerebellar vermis. A syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation. Neurology 19:813–825PubMed

25.

Gleeson JG, Keeler LC, Parisi MA et al (2004) Molar tooth sign of the midbrain–hindbrain junction: occurrence in multiple distinct syndromes. Am J Med Genet 125:125–134CrossRef

26.

Beales PL, Elcioglu N, Woolf AS, Parker D, Flinter FA (1999) New criteria for improved diagnosis of Bardet–Biedl syndrome: results of a population survey. J Med Genet 36:437–446PubMed

27.

Chen CP (2007) Meckel syndrome: genetics, perinatal findings, and differential diagnosis. Taiwan J Obstet Gynecol 46:9–14PubMedCrossRef

28.

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

29.

Valente EM, Brancati F, Dallapiccola B (2008) Genotypes and phenotypes of Joubert syndrome and related disorders. Eur J Med Genet 51:1–23PubMedCrossRef

30.

Ansley SJ, Badano JL, Blacque OE et al (2003) Basal body dysfunction is a likely cause of pleiotropic Bardet–Biedl syndrome. Nature 425:628–633PubMedCrossRef

31.

Ferrante MI, Zullo A, Barra A et al (2006) Oral–facial–digital type I protein is required for primary cilia formation and left–right axis specification. Nat Genet 38:112–117PubMedCrossRef

32.

Parisi MA, Bennett CL, Eckert ML et al (2004) The NPHP1 gene deletion associated with juvenile nephronophthisis is present in a subset of individuals with Joubert syndrome. Am J Hum Genet 75:82–91PubMedCrossRef

33.

Valente EM, Marsh SE, Castori M (2005) Distinguishing the four genetic causes of Jouberts syndrome-related disorders. Ann Neurol 57:513–519PubMedCrossRef

34.

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

35.

Barkovich AJ, Kjos BO, Norman D, Edwards MS (1989) Revised classification of posterior fossa cysts and cystlike malformations based on the results of multiplanar MR imaging. AJR Am J Roentgenol 153:1289–1300PubMed

36.

Raybaud C, Girard N, Sevely A, Leboucq N (1996) Neuroradiologie pediatrique (I). In: Raybaud C, Girard N, Sevely A, Leboucq N (eds) Radiodiagnostic–neuroradiologie–appariel locomoteur. Elsevier, Paris, p 26

37.

Barkovich AJ (2005) Congenital malformations of the brain and skull. In: Barkovich AJ (ed) Pediatric neuroimaging, 4th edn. Lippincott Williams and Wilkins, Philadelphia, pp 291–440

38.

Tortori-Donati P, Fondelli MP, Rossi A, Carini S (1996) Cystic malformations of the posterior cranial fossa originating from a defect of the posterior membranous area. Mega cisterna magna and persisting Blake’s pouch: two separate entities. Childs Nerv Syst 12:303–308PubMedCrossRef

39.

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

40.

Bonnevie K, Brodal A (1946) Hereditary hydrocephalus in the house mouse. VI. The development of cerebellar anomalies during fetal life with notes on the normal development of the mouse cerebellum. Lkr Norske Vidensk Akad Oslo 1 Matj-nat KI 4:4–60

41.

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

42.

Grinberg I, Northrup H, Ardinger H, Prasad C, Dobyns WB, Millen KJ (2004) Heterozygous deletion of the linked genes ZIC1 and ZIC4 is involved in Dandy–Walker malformation. Nat Genet 36:1053–1055PubMedCrossRef

43.

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

44.

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

45.

Donkelaar HJ, Wesseling P, Lammens M, Renier WO, Mullaart RA, Thijssen HO (2001) Development and the developmental disorders of human brain. I. Early development of the cerebrum. Ned Tijdschr Geneeskd 145:345–353PubMed

46.

Ramaekers VT, Heimann G, Reul J, Thron A, Jaeken J (1997) Genetic disorders and cerebellar structural abnormalities in childhood. Brain 120:1739–1751PubMedCrossRef

47.

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

48.

Soto-Ares G, Delmaire C, Deries B, Vallee L, Pruvo JP (2000) Cerebellar cortical dysplasia: MR findings in a complex entity. AJNR Am J Neuroradiol 21:1511–1519PubMed

49.

Soto-Ares G, Devisme L, Jorriot S, Deries B, Pruvo JP, Ruchoux MM (2002) Neuropathologic and MR imaging correlation in a neonatal case of cerebellar cortical dysplasia. AJNR Am J Neuroradiol 23:1101–1104PubMed

50.

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 135:134–141PubMed

Title: Malformations of the Midbrain and Hindbrain: A Retrospective Study and Review of the Literature
Authors: Ozlem Alkan
Osman Kizilkilic
Tulin Yildirim
Publication date: 01-09-2009
Publisher: Springer-Verlag
Published in: The Cerebellum / Issue 3/2009
Print ISSN: 1473-4222
Electronic ISSN: 1473-4230
DOI: https://doi.org/10.1007/s12311-009-0104-x

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Malformations of the Midbrain and Hindbrain: A Retrospective Study and Review of the Literature

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