Acta Neuropathologica

, Volume 30, Issue 2, pp 91–107 | Cite as

Pierre Robin Syndrome

Clinical, light and electron-microscopic and biochemical observations in a case
  • Catherine Haberland
  • Aruna Daniels
  • Glyn Dawson
Original Investigations


Clinical, light and electron-microscopic, and biochemical observations are presented in an 11 years old boy with Pierre Robin Syndrome; micrognathia, cleft palate and glossoptosis. Respiratory distress and feeding difficulties were early and serious complications of the glossoptosis. “Cachexia”, a striking physical underdevelopment, profound psychomotor retardation and epilepsy constituted the prominent clinical features. The neuropathology of the syndrome was characterized by the following: 1. Arrest in cerebral growth and maturation; 2. Mild diffuse and laminar cortical neuronal losses and astrocytic fibrosis; and 3. Minor histogenetic anomaly in the cerebellar cortex.

The arrest in cerebral development was reflected grossly by microencephaly and, histologically by “immaturity” of numerous cortical neurons, poverty of intracortical fibrillary plexuses, poor establishment of cytoarchitectonic characteristics and hypoplasia of hemispheric white matter. At subcellular level, there was diminution of cytoplasmic organelles, particularly the rough endoplasmic reticulum. A marked deficiency in myelin lipids and severe diminution of total ganglioside concentration in the cerebral cortex were the major biochemical findings.

In the pathogenesis of cerebral alterations congenital factors and the complications of “glossoptosis” were considered. It was suggested that the early undernutrition played an important role in the impediment of cerebral growth and maturation. The cerebral hypoxic insults further curtailed the development of already compromised neurons and depressed their functional activities, particularly in the more susceptible cerebral cortex. It was proposed that the arrested brain development provided a substantial structural basis for the psychomotor retardation.

Key words

Pierre Robin Syndrome Neuropathology Biochemistry Undernutrition Cerebral Hypoxia Cerebral Development Mental Retardation 


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  1. Adams, C. W. M., Davison, A. N.: The occurrence of esterified cholesteral in the developing nervous system. J. Neurochem.4, 282–289 (1959)Google Scholar
  2. Ambrosius, K. D.: Inanition-Malnutrition. In: Minckler (ed.) Pathology of the Nervous System, vol. 2, pp. 1578–1583. New York: McGraw Co. 1971Google Scholar
  3. Baker, R. D.: Postmortem Examination, Specific Methods and Procedures. Philadelphia: W. B. Saunders Co. 1967Google Scholar
  4. Bass, N. H., Netsky, M. G., Young, E.: Effect of neonatal malnutrition on developing cerebrum: I. Microchemical and histological study of cellular differentiation in the rat. Arch. Neurol. (Chic.)23, 289–302 (1970)Google Scholar
  5. Bass, N. H., Netsky, M. G., Young, E.: Effect of neonatal malnutrition on developing brain. II. Microchemical and histological study of myelin formation in the rat. Arch. Neurol. (Chic.)23, 303–313 (1970)Google Scholar
  6. Benton, J. W., Moser, H. W., Dodge, P. R., Carr, S.: Modification of the schedule of myelination in the rat by early nutritional deprivation. Pediatrics38, 801–807 (1966)Google Scholar
  7. Brown, A. W., Brierley, J. B.: The nature and time course of anoxic-ischemic cell change in the rat brain. An optical and electron microscopic study. In: Brierley, J. B., Meldrum, B. S. (eds.). Brain hypoxia, pp. 49–60. London: William Heineman, Ltd. 1971Google Scholar
  8. Caley, D. W., Maxwell, D. S.: An electron microscopic study of neurons during postnatal development of the rat cerebral cortex. J. comp. Neurol.133, 17–44 (1968)Google Scholar
  9. Chase, H. P., Dorsey, J., McKhann, G. M.: The effect of malnutrition on the synthesis of a myelin lipid. Pediatrics40, 551–560 (1967)Google Scholar
  10. Chase, H. P., Harold, M. P.: Undernutrition and child development. New Engl. J. Med.282, 934–939 (1970)Google Scholar
  11. Chase, H. P., Lindsley, W. F. B., O'Brien, D.: Undernutrition and cerebellar development. Nature (Lond.)221, 554–555 (1969)Google Scholar
  12. Clamp, J. R., Dawson, G., Hough, L.: The simultaneous estimation of 6-deoxy-l-galactose (l-fucose),d-mannose,d-galactose, 2-acetamido-2-deoxy-d-glucose (N-acetyl-d-glucosamine) andN-Acetylneuraminic acid (sialic acid) in glycopeptides and glyco-proteins. Biochim. biophys. Acta (Amst.)148, 342–349 (1967)Google Scholar
  13. Conel, L. J.: The postnatal development of the human cerebral cortex, vol. 1–6 Cambridge, Massachusetts: University Press 1939–1967Google Scholar
  14. Cravioto, J., DeLincardie, E. R., Birch, H. G.: Nutrition, growth, and neurointegrative development: An experimental and Ecologic study. Pediatrics38, 318–372 (1966)Google Scholar
  15. Crome, L., Stern, J.: The pathology of mental retardation, Boston: Little Brown and Co. 1967Google Scholar
  16. Davison, A. N., Dobbing, J.: The developing brain. In Applied neurochemistry. London: Blackwell Sci. Publ. 1968Google Scholar
  17. Davison, A. N., Peters, A.: Myelination. Springfield, Ill.: Ch. C. Thomas 1970Google Scholar
  18. Dawson, G.: Glycosphingolipids levels in an unusual neurovisceral storage disease characterized by lactosylceramide galactosyl hydrolase deficiency: Lactosylceramidosis. J. Lipid Res.13, 207–219 (1972)Google Scholar
  19. Dawson, G., Matalon, R., Dorfman, A.: Glycosphingolipids in cultured human skin fibroblasts II. Characterization and metabolism in fibroblasts from patients with inborn errors of glycosphingolipids and mucopolysaccharide metabolism. J. biol. Chem.246, 5951–5958 (1972)Google Scholar
  20. Dennison, W. M.: The Pierre Robin Syndrome Pediatrics36, 336–341 (1965)Google Scholar
  21. Dobbing, J.: Unternutrition and the developing brain: The use of animal models to elucidate the human problem. In: Paoletti, R., Davison, A. N. (eds.) Chemistry and brain development. New York: Plenum Press 1971Google Scholar
  22. Dobbing, J.: Undernutrition and the Developing Brain: The relevance of animal models to the human problem. Amer. J. Dis. Child.120, 411–415 (1970)Google Scholar
  23. Drewes, L. R., Gilboe, D. D., Betz, A. L.: Metabolic alterations in brain during anoxicanoxia and subsequent recovery. Arch. Neurol. (Chic.)29, 385–390 (1973)Google Scholar
  24. Eayrs, J. T., Horn, G.: The development of cerebral cortex in hypothyroid and starved rats. Anat. Rec.121, 53–62 (1955)Google Scholar
  25. Fishman, M. A., Madyastha, P., Prensky, A. L.: The effect of undernutrition of the development of myelin in the rat central nervous system. Lipids6, 458–465 (1971)Google Scholar
  26. Fishman, M. A., Prensky, A. L., Dodge, P. R.: Low content of cerebral lipids in infants suffering from malnutrition. Nature (Lond.)221, 552–553 (1969)Google Scholar
  27. Folch, J., Lees, M., Sloan-Stanley, M. G.: A simple method for the isolation and purification of total lipids from animal tissues. J. biol. Chem.226, 497–509 (1957)Google Scholar
  28. Fox, J. H., Fishman, M. A., Dodge, P. R., Prensky, A. L.: The effect of malnutrition on human central nervous system myelin. Neurology (Minneap)22, 1213–1216 (1972)Google Scholar
  29. Freytag, E., Lindenberg, R.: Neuropathologic findings in patients of a hospital for the mentally deficient. A survey of 359 cases. Johns Hopk. med. J.121, 379 (1967)Google Scholar
  30. Grossman, R. G., Williams, V. F.: Electrical activity and ultrastructure of cortical neurons and synapses in ischemia. In: Brierley, J. B., Meldrum, B. S. (eds.) Brain Hypoxia, pp. 61–75 London: Willaim Heineman Medical Books, Ltd. 1971Google Scholar
  31. Hossmann, K.: Kleihues: Reversibility of ischemic brain damage. Arch. Neurol. (Chic.)29, 375–382 (1973)Google Scholar
  32. Huttenlocher, P. R.: Dndritic development in neocortex of children with mental defect and infantile spasm. Neurology (Minneap.)24, 203–210 (1974)Google Scholar
  33. Jarlstedt, J., Hultborn, R.: Experimental Alcoholism in rats: RNA content and composition in isolated cerebellar Purkinje cells after long-term treatment. J. Neuropath. exp. Neurol.31, 347–351 (1972)Google Scholar
  34. Jeresaty, R. M., Huszar, R. J., Basu, S.: Pierre Robin Syndrome. Cause of respiratory obstruction, cor pulmonale, and pulmonary edema. J. Dis. Child.117, 710–716 (1969)Google Scholar
  35. Kornguth, S. E., Anderson, J. W., Scott, G.: Observations on the ultrastructure of the developing cerebellum of the macaca mulatta. J. comp. Neurol.120, 1–22 (1967)Google Scholar
  36. Little, J. R., Kerr, W. L., Sundt, T. M., Jr.: The role of lysosomes in production of ischemic nerve changes. Arch. Neurol. (Chic.)30, 448–455 (1974)Google Scholar
  37. Manocha, S. L.: Malnutrition and retarded human development. Springfield, Ill. Ch. C. Thomas 1972Google Scholar
  38. McKenzie, J.: The first arch syndrome. Develop. Med. Child. Neurol.8, 55–66 (1966)Google Scholar
  39. Muralt, A.: The developing brain and the damage inflicted by malnutrition. An introduction. In: Lipids, malnutrition and the developing brain. A Ciba Foundation Symposium New York: Elsevier Sci. Publ. 1972Google Scholar
  40. Platt, B. S., Stewart, B. S.: Effects of protein-calorie deficiency on dogs. 2. Morphological changes in the nervous system. Develop. Med. Child Neurol.11, 174–192 (1969)Google Scholar
  41. Robin, P.: Glossoptosis due to atresia and hypotrophy of the mandible. Amer. J. Dis. Child.48, 541–547 (1934)Google Scholar
  42. Rörke, L. B., Riggs, H. R.: Myelination of the brain in the newborn. Philadelphia: J. B. Lippincott Co. 1969Google Scholar
  43. Rosso, Hormazabal, J., Winick, M.: Changes in brain weight, cholesterol, phospholipid and DNA content in maramic children. Amer. J. clin. Nutr.23, 1275 (1970)Google Scholar
  44. Rouser, G., Fleischer, S., Yamamoto, A.: Two-dimensional thin-layer chromatographic separation of polar lipids and determiation of phospholipids by phosphorus analysis of spots. Lipids5, 494–496 (1970)Google Scholar
  45. Rubiolo de Macciono, A. H., Caputto, R. J.: Synthesis of gangliosides during development and its relation to the quantitative changes of subcellular particles of rat brain. J. Neurochem.15, 1257–1264 (1968)Google Scholar
  46. Sachtleben, P.: Zur Pathogenese und Therapie des Pierre-Robin Syndromes. Arch. Kinderheilk.171, 55–63 (1964)Google Scholar
  47. Sacrez, R., Francfort, J. J., Gigonnet, J. M., Beauvais, P., Boll, G.: A Propos de la debilité intellectuelle et d'anomalies associées à la triade symptomatique du syndrome de Pierre Robin. Ann. Pédiat.2, 28–33 (1967)Google Scholar
  48. Smith, J. L., Stowe, F. R.: The Pierre Robin Syndrome (Glossoptosis, Micrognathis, Cleft Palate). A review of 39 cases with emphasis on accociated ocular lesions. Pediatrics27, 128–133 (1961)Google Scholar
  49. Spector, R. G.: Enzyme chemistry of anoxic brain injury. In: Adams, C. W. M. (ed.) Neurohistochemistry, p. 547. Amsterdam: Elsevier Publ. 1965Google Scholar
  50. Stoch, M. B., Smhthe, P. M.: Does undernutrition during infancy inhibit brain growth and subsequent intellectual development? Arch. Dis. Childh.38, 546–552 (1963)Google Scholar
  51. Suzuki, K.: The pattern of mammalian brain gangliosides II, Regional and development differences. J. Neurochem.12, 969–979 (1965)Google Scholar
  52. Tettamanti, G.: Brain Gangliosides in Development. In: Paoletti, R., Davison, A. N. (eds.): Chemistry and brain development. New York: Plenum Press 1971Google Scholar
  53. Vance De, Sweeley, C. C.: Quantitative determination of the neutral glycosylceramides in human blood. J. Lipid. Res.8, 621–630 (1967)Google Scholar
  54. Weigandt, H.: Recent advances on the chemistry and localization of brain gangliosides and related glycosphingolipids, Tettamanti, G., Arrigoni, M. (eds.) In: Glycolipids, Glycoproteins, and mucopolysaccharides of the nervous system. New York: Plenum Press 1972Google Scholar
  55. Winick, M., Brasel, J. A., Rosso, P.: Nutrition and cell growth. In: Nutrition and Development, Winick, M. (ed.). New York: Joan Wiley and Sons 1972Google Scholar
  56. Winick, M., Noble, A.: Cellular response in rats during malnutrition at various ages. J. Nutr.89, 300–306 (1966)Google Scholar
  57. Winick, M., Rosso, P.: Head circumference and cellular growth in normal and marasmic children. J. Pediat.74, 774–778 (1969)Google Scholar
  58. Winick, M., Rosso, P.: The effect of severe early malnutrition on cellular of human brain. Pediat. Res.3, 181–184 (1969)Google Scholar
  59. Winick, M., Rosso, P., Brasel, J. A.: Malnutrition and cellular growth in the brain: Existencen of critical periods. In: Lipids, malnutrition and the developing brain. A Ciba Foundation Symposium. New York: Elsevier Sci. Publ. 1972Google Scholar
  60. Yakovley, P. I., Lecours, A. R.: The myelogenetic cycles of regional maturation of the brain. In: Regional development of the brain in early life, Minkowski, A. (ed.) Philadelphia: F. A. Davis Co. 1967Google Scholar
  61. Yanagihara, T.: Effect of anoxia on protein metabolism in subcellular fractions of rabbit brain. Stroke5, 226–229 (1974)Google Scholar

Copyright information

© Springer-Verlag 1974

Authors and Affiliations

  • Catherine Haberland
    • 1
    • 2
    • 3
  • Aruna Daniels
    • 1
    • 2
  • Glyn Dawson
    • 1
    • 2
  1. 1.Department of NeuropathologyIllinois State Psychiatric and Pediatric InstitutesChicagoUSA
  2. 2.Departments of Pathology, Pediatrics, and Biochemistry of The University of ChicagoChicagoUSA
  3. 3.Illinois Masonic Medical CenterChicagoUSA

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