Summary
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adams, C. W. M., Davison, A. N.: The occurrence of esterified cholesteral in the developing nervous system. J. Neurochem.4, 282–289 (1959)
Ambrosius, K. D.: Inanition-Malnutrition. In: Minckler (ed.) Pathology of the Nervous System, vol. 2, pp. 1578–1583. New York: McGraw Co. 1971
Baker, R. D.: Postmortem Examination, Specific Methods and Procedures. Philadelphia: W. B. Saunders Co. 1967
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)
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)
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)
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. 1971
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)
Chase, H. P., Dorsey, J., McKhann, G. M.: The effect of malnutrition on the synthesis of a myelin lipid. Pediatrics40, 551–560 (1967)
Chase, H. P., Harold, M. P.: Undernutrition and child development. New Engl. J. Med.282, 934–939 (1970)
Chase, H. P., Lindsley, W. F. B., O'Brien, D.: Undernutrition and cerebellar development. Nature (Lond.)221, 554–555 (1969)
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)
Conel, L. J.: The postnatal development of the human cerebral cortex, vol. 1–6 Cambridge, Massachusetts: University Press 1939–1967
Cravioto, J., DeLincardie, E. R., Birch, H. G.: Nutrition, growth, and neurointegrative development: An experimental and Ecologic study. Pediatrics38, 318–372 (1966)
Crome, L., Stern, J.: The pathology of mental retardation, Boston: Little Brown and Co. 1967
Davison, A. N., Dobbing, J.: The developing brain. In Applied neurochemistry. London: Blackwell Sci. Publ. 1968
Davison, A. N., Peters, A.: Myelination. Springfield, Ill.: Ch. C. Thomas 1970
Dawson, G.: Glycosphingolipids levels in an unusual neurovisceral storage disease characterized by lactosylceramide galactosyl hydrolase deficiency: Lactosylceramidosis. J. Lipid Res.13, 207–219 (1972)
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)
Dennison, W. M.: The Pierre Robin Syndrome Pediatrics36, 336–341 (1965)
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 1971
Dobbing, J.: Undernutrition and the Developing Brain: The relevance of animal models to the human problem. Amer. J. Dis. Child.120, 411–415 (1970)
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)
Eayrs, J. T., Horn, G.: The development of cerebral cortex in hypothyroid and starved rats. Anat. Rec.121, 53–62 (1955)
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)
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)
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)
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)
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)
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. 1971
Hossmann, K.: Kleihues: Reversibility of ischemic brain damage. Arch. Neurol. (Chic.)29, 375–382 (1973)
Huttenlocher, P. R.: Dndritic development in neocortex of children with mental defect and infantile spasm. Neurology (Minneap.)24, 203–210 (1974)
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)
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)
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)
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)
Manocha, S. L.: Malnutrition and retarded human development. Springfield, Ill. Ch. C. Thomas 1972
McKenzie, J.: The first arch syndrome. Develop. Med. Child. Neurol.8, 55–66 (1966)
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. 1972
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)
Robin, P.: Glossoptosis due to atresia and hypotrophy of the mandible. Amer. J. Dis. Child.48, 541–547 (1934)
Rörke, L. B., Riggs, H. R.: Myelination of the brain in the newborn. Philadelphia: J. B. Lippincott Co. 1969
Rosso, Hormazabal, J., Winick, M.: Changes in brain weight, cholesterol, phospholipid and DNA content in maramic children. Amer. J. clin. Nutr.23, 1275 (1970)
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)
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)
Sachtleben, P.: Zur Pathogenese und Therapie des Pierre-Robin Syndromes. Arch. Kinderheilk.171, 55–63 (1964)
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)
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)
Spector, R. G.: Enzyme chemistry of anoxic brain injury. In: Adams, C. W. M. (ed.) Neurohistochemistry, p. 547. Amsterdam: Elsevier Publ. 1965
Stoch, M. B., Smhthe, P. M.: Does undernutrition during infancy inhibit brain growth and subsequent intellectual development? Arch. Dis. Childh.38, 546–552 (1963)
Suzuki, K.: The pattern of mammalian brain gangliosides II, Regional and development differences. J. Neurochem.12, 969–979 (1965)
Tettamanti, G.: Brain Gangliosides in Development. In: Paoletti, R., Davison, A. N. (eds.): Chemistry and brain development. New York: Plenum Press 1971
Vance De, Sweeley, C. C.: Quantitative determination of the neutral glycosylceramides in human blood. J. Lipid. Res.8, 621–630 (1967)
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 1972
Winick, M., Brasel, J. A., Rosso, P.: Nutrition and cell growth. In: Nutrition and Development, Winick, M. (ed.). New York: Joan Wiley and Sons 1972
Winick, M., Noble, A.: Cellular response in rats during malnutrition at various ages. J. Nutr.89, 300–306 (1966)
Winick, M., Rosso, P.: Head circumference and cellular growth in normal and marasmic children. J. Pediat.74, 774–778 (1969)
Winick, M., Rosso, P.: The effect of severe early malnutrition on cellular of human brain. Pediat. Res.3, 181–184 (1969)
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. 1972
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. 1967
Yanagihara, T.: Effect of anoxia on protein metabolism in subcellular fractions of rabbit brain. Stroke5, 226–229 (1974)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Haberland, C., Daniels, A. & Dawson, G. Pierre Robin Syndrome. Acta Neuropathol 30, 91–107 (1974). https://doi.org/10.1007/BF00685436
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00685436