Acta Neuropathologica

, Volume 63, Issue 3, pp 218–228 | Cite as

Neuropathologic findings in thanatophoric dysplasia

  • K. -L. Ho
  • C. -H. Chang
  • S. Samuel Yang
  • J. L. Chason
Original Works


Neuropathologic study of eight cases of thanatophoric dysplasia (dwarfism) reveals developmental abnormalities including hypoplasia of posterior fossa, megalencephaly, cerebral gyral disorganization, hippocampal malformation, neuronal heterotopia, nuclear dysplasia, and abnormal axonal bundles. There are no noticeable differences in CNS abnormalities between thanatophoric dysplasia with and without cloverleaf skull (Kleeblattschädel). The CNS abnormalities, likely the result of abnormal neuronal migration and cytoarchitectonic disarrangement, are apparently not caused by skeletal abnormalities. The observation suggests that CNS abnormalities represent a characteristic and distinct manifestation of thanatophoric dysplasia.

Key words

Thanatophoric dysplasia (dwarfism) Cloverleaf skull (Kleeblattschädel) Hippocampal malformation Neuronal migration Neuronal heterotopia Neuropathologic findings 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Altman J (1976) Experimental reorganization of the cerebellar cortex. VII. Effects of late-x-irradiation schedules that interfere with cell acquisition after stellate cells are formed. J Comp Neurol 165:65–76Google Scholar
  2. 2.
    Beiley OT (1936) Relation of glioma of the leptomeninges to neuroglial nests. Report of a case of astrocytoma of the leptomeninges. Arch Pathol 21:584–601Google Scholar
  3. 3.
    Bailey P, Bucy PC (1931) The origin and nature of meningeal tumors. Am J Cancer 15:15–35Google Scholar
  4. 4.
    Bloomfield JA (1970) Cloverleaf skull and thanatophoric dwarfism. Aust Radiol 14:429–434Google Scholar
  5. 5.
    Brun A (1965) Marginal glioneural heterotopias of the central nervous system. Acta Pathol Microbiol Scand 65:221–233Google Scholar
  6. 6.
    Caviness VS, Jr, Evrard P, Lyon G (1978) Radial neuronal assemblies, ectopia and necrosis of developing cortex: A case analysis. Acta Neuropathol (Berl) 41:67–72Google Scholar
  7. 7.
    Caviness VS, Sidman RL (1973) Time of orgin of corresponding cell classes in the cerebral cortex of normal and reeler mutant mice. An autoradiographic analysis. J Comp Neurol 148:141–152Google Scholar
  8. 8.
    Choi BH, Lapham LW, Amin-Zaki L, Saleem T (1978) Abnormal neuronal migration, deranged cerebral cortical organization, and diffuse white matter astrocytosis of human fetal brain: A major effect of methylmercury poisoning in utero. J Neuropathol Exp Neurol 37:719–733Google Scholar
  9. 9.
    Cooper IS, Kernohan JW (1951) Heterotopic glial nests in the subarachnoid space: Histopathologic characteristics, mode of origin and relation to meningeal gliomas. J Neuropathol Exp Neurol 10:16–29Google Scholar
  10. 10.
    Danes BS (1974) Achondroplasia and thanatophoric dwarfism. A study in cell culture. Birth Defects 10:37–42Google Scholar
  11. 11.
    Dvorak K, Feit J, Jurankova Z (1978) Experimentally induced focal microgyria and status verrucous deformis in rats: Pathogenesis and interrelation. Histological and autoradiographical study. Acta Neuropathol (Berl) 44:121–129Google Scholar
  12. 12.
    Friede RL (1975) Developmental neuropathology. Springer, Berlin Heidelberg New York, pp 351–355Google Scholar
  13. 13.
    Goutieres F, Aicardi J, Bargeton E (1971) Une malformation cerebrale particulière associée au narisme thanatophore. Rev Neurol 125:435–440Google Scholar
  14. 14.
    Hicks SP, D'Amato CJ, Coy MA, O'Brien ED, Thurston JS, Joftes DL (1968) Migrating cells in the developing central nervous system studied by radiosensitivity and tritiated thymidine uptake. Bookhaven Symp Biol 14: 246–304Google Scholar
  15. 15.
    Ho KL (1983) Concurrence of subependymoma and heterotopic leptomeningeal neuroglial tissue. Arch Pathol Lab Med 107:136–140Google Scholar
  16. 16.
    Hori A, Friede RL, Fisher G (1983) Ventricular diverticles with localized dysgenesis of the temporal lobe in cloverleaf skull anomaly. Acta Neuropathol (Berl) 60:132–136Google Scholar
  17. 17.
    Horton WA, Harris DJ, Collins DL (1983) Discordance for the Kleeblattschädel anomaly in monozygotic twins with thanatophoric dysplasia. Am J Med Genet 15:97–101Google Scholar
  18. 18.
    Huguenin M, Godard C, Ferrier PE, Bamatter F (1968) Two different mutations within the same sibship: thanatophoric dwarfism and Ullrich-Feichtiger syndrome. Helv Paediatr Acta 24:239–245Google Scholar
  19. 19.
    Iannacione G, Gerline (1974) The so-called “cloverleaf skull syndrome”. Pediatr Radiol 2:175–184Google Scholar
  20. 20.
    Keats TE, Riddervold HO, Michaelis LL (1970) Thanatophoric dwarfism. Am J Roentgenol 108:473–480Google Scholar
  21. 21.
    Klatzo I (1975) Pathophysiologic aspects of cerebral ischemia. In: Tower DB (ed) The nervous system, vol. 1: The basic neurosciences. Raven Press, New York, pp 313–332Google Scholar
  22. 22.
    Langman J, Schimada M (1971) Cerebral cortex of mouse after prenatal chemical insults. Am J Anat 132:355–374Google Scholar
  23. 23.
    Levine DN, Fisher MA, Caviness VS, Jr (1974) Porencephaly with microgyria: A pathologic study. Acta Neuropathol (Berl) 29:99–113Google Scholar
  24. 24.
    Maroteaux P, Lamy M, Robert JM (1967) Le nanisme thanatophore. Presse Med 75:2519–2524Google Scholar
  25. 25.
    Martinelli B, Campailla E, Ferrari G (1975) Malformation cerebrale particulière et nanism thanatophore. Arch Fr Pediatr 32:455–460Google Scholar
  26. 26.
    McBride MC, Kemper TL (1982) Pathogenesis of four layered microgyric cortex in man. Acta Neuropathol (Berl) 57:93–98Google Scholar
  27. 27.
    Partington MW, Gonzales-Crussi F, Khakee SG, Wollin DG (1971) Cloverleaf skull and thanatophoric dwarfism. Arch Dis Child 46:656–664Google Scholar
  28. 28.
    Rakic P, Sidman RL (1970) Histogenesis of cortical layers in human cerebellum, particularly the lamina dissecans. J Comp Neurol 139:473–500Google Scholar
  29. 29.
    Rakic P (1974) Neurons in rhesus monkey visual cortex: Systematic relation between time of origin and eventual disposition. Science 183:425–427Google Scholar
  30. 30.
    Rakic P (1972) Mode of cell migration to the superficial layers of fetal monkey neocortex. J Comp Neurol 145:61–84Google Scholar
  31. 31.
    Richman DP, Stewart RM, Cavines US (1974) Cerebral microgyria in a 27-week fetus: An architectonic and topographic analysis. J Neuropathol Exp Neurol 33:374–384Google Scholar
  32. 32.
    Sabry A (1974) Thanatophoric dwarfism in triplets. Lancet II:533Google Scholar
  33. 33.
    Saldino RM (1971) Lethal short-limbed dwarfism: Achondrogenesis and thanatophoric dwarfism. Am J Roentgenol 112:185–197Google Scholar
  34. 34.
    Sato D, Hosokawa Y, Nakamura Y, Mukae T, et al. (1981) Thanatophoric dysplasia of identical twins. Acta Pathol Jpn 31:895–902Google Scholar
  35. 35.
    Sewell AC, Spranger JW, Pennock CA (1977) Epiphyseal cartilage chemistry in thanatophoric dwarfism. Lancet I:854Google Scholar
  36. 36.
    Shah K, Astley R, Cameron AH (1973) Thanatophoric dwarfism. J Med Genet 10:243–252Google Scholar
  37. 37.
    Shimada M, Abe Y, Yamano T, Ohta S, Yaniazaki S, Ohya N (1982) The pathogenesis of abnormal cytoarchitecture in the cerebral cortex and hippocampus of the mouse treated transplacentally with cytosine arabinoside. Acta Neuropathol (Berl) 58:159–167Google Scholar
  38. 38.
    Sidman RL, Rakic P (1973) Neuronal migration, with special reference to developing human brain: A review. Brain Res 62:1–35Google Scholar
  39. 39.
    Sillence DO, Horton WA, Rimoin DL (1979) Morphologic studies in the skeletal dysplasia. A review. Am J Pathol 96:813–860Google Scholar
  40. 40.
    Singh SC (1980) Deformed dendrites and reduced spine numbers on ectopic neurons in the hippocampus of rats exposed to methylazoxymethanol acetate. A Golgi-Cox study. Acta Neuropathol (Berl) 49:193–198Google Scholar
  41. 41.
    Spranger JW, Langer LO, Wiedemann H-R (1974) Bone dysplasia. An atlas of constitutional disorders of skeletal development. Saunders, Philadelphia, pp 38–40Google Scholar
  42. 42.
    Thompson FH, Parmley TH (1971) Obstetric features of thanatophoric dwarfism. Am J Obstet Gynecol 109:396–401Google Scholar
  43. 43.
    Volpe JJ, Adams RD (1972) Cerebro-hepato-renal syndrome of Zellweger: An inherited disorder of neuronal migration. Acta Neuropathol (Berl) 20:175–198Google Scholar
  44. 44.
    Webster W, Shimada M, Langman J (1973) Effects of fluorodenoxyridine on developing neocortex of the mouse. Am J Anat 137:67–81Google Scholar
  45. 45.
    Wolbach SB (1907) Congenital rhabdomyoma of the heart. Report of a case associated with multiple nests of neuroglial tissue in the meninges of the spinal cord. J Med Res 16:495–520Google Scholar
  46. 46.
    Wongmongkolrit T, Bush M, Roessmmann U (1983) Neuropathological findings in thanatophoric dysplasia. Arch Pathol Lab Med 107:132–135Google Scholar
  47. 47.
    Yang SS, Heidelberger KP, Brough AJ, Corbett DP, Berstein J, (1976) Lethal short-limbed chondrodysplasia in early infancy. In: Rosenberg HS, Bolande RP (eds) Perpectives in pediatric pathology, vol 3. Year Book Medical Publishers, Chicago, pp 1–40Google Scholar
  48. 48.
    Young RS, Pochaczevsky R, Leonidas JC, Wexler IB, Rather H (1973) Thanatophoric dwarfism and cloverleaf skull (“Kleeblattschädel”). Pediatr Radiol 106:401–405Google Scholar
  49. 49.
    Zellweger H, Taylor B (1965) Genetic aspects of achondroplasia. Lancet I:8–16Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • K. -L. Ho
    • 1
  • C. -H. Chang
    • 2
  • S. Samuel Yang
    • 3
  • J. L. Chason
    • 1
  1. 1.Dept. of PathologyHenry Ford HospitalDetroitUSA
  2. 2.Dept. of Pathology, Children's Hospital of MichiganWayne State University School of MedicineDetroitUSA
  3. 3.Dept. of PathologyWilliam Beaumont HospitalRoyal OakUSA

Personalised recommendations