Abstract
The neuropathological findings at autopsy in four cases of type I and three of type II lissencephaly are presented. Type I lissencephaly is characterized by agyriapachygyria with a markedly thickened cerebral cortex with four coarse histological layers. The normally myelinated white matter, often with neuronal heterotopias, is very narrow, and the gray-to-white matter ratio is inverted (about 4:1); there are no white-gray interdigitations. Claustrum and capsula extrema are absent. Ventricular dilatation is present, especially of the occipital horns. In the hypoplastic brain stem large olivary heterotopias can often be observed. Severe cerebellar malformations, obstructive hydrocephalus, severe eye abnormalities, and congenital muscular dystrophy are not seen. Clinically, type I lissencephaly presents as “isolated lissencephaly sequence” or as “Miller-Dieker syndrome” with characteristic facial dysmorphism. The long survival of 20 years achieved by one of our patients is very uncommon. Type II lissencephaly is characterized by widespread agyria. Usually, obstructive hydrocephalus is present with a thin cerebral mantle showing a slightly thickened cortex and a narrow, hypomyelinated white matter often with neuronal heterotopias (gray-to-white matter ratio about 1:1). The border between gray and white matter is blurred. Claustrum and capsula extrema are absent. Histologically, the cortex appears disorganized without layering; widespread leptomeningeal gliomesenchymal proliferations and glioneuronal heterotopias are present. Hydrocephalus is caused by obstruction of the subarachnoid space, aqueductal stenosis, and Dandy-Walker malformation. The latter is a typical finding in type II lissencephaly together with severe cerebellar cortical dysplasias. Aplasia of the olfactory nerves, gliotic fusion of the frontal lobes, and an occipital cephalocele may be found. Type II lissencephaly occurs in clinical syndromes with severe eye abnormalities and congenital muscular dystrophy (the so-called “Walker-Warburg syndrome”). The congenital muscular dystrophies have no dystrophin deficiency, as we were able to show immunohistochemically in the muscle biopsies of two further patients with this syndrome.
Similar content being viewed by others
References
Aicardi J (1991) The agyria-pachygyria complex: a spectrum of cortical malformations. Brain Dev 13: 1–8
Barkovich AJ, Koch TK, Carrol CL (1991) The spectrum of lissencephaly: report of ten patients analyzed by magnetic resonance imaging. Ann Neurol 30: 139–146
Barth PG (1987) Disorders of neuronal migration. Can J Neurol Sci 14: 1–16
Barth PG, Mullaart R, Stam FC, Slooff JL (1982) Familial lissencephaly with extreme neopallial hypoplasia. Brain Dev 4: 145–151
Bordarier C, Aicardi J, Goutieres F (1984) Congenital hydrocephalus and eye abnormalities with severe developmental brain defects: Warburg's syndrome. Ann Neurol 16: 60–65
Bordarier C, Robain O Rethoré MO Dulac O, Dhellemes C (1986) Inverted neurons in agyria. A Golgi study of a case with abnormal chromosome 17. Hum Genet 73: 374–378
Dambska M, Wisniewski K, Sher J, Solish G (1982) Cerebrooculo-muscular syndrome: a variant of Fukuyama congenital cerebromuscular dystrophy. Clin Neuropathol 1: 93–98
Dambska M, Wisniewski K, Sher JH (1983) Lissencephaly: two distinct clinico-pathological types. Brain Dev 5: 302–310
Daube JR, Chou SM (1966) Lissencephaly: two cases. Neurology 16: 179–191
De Rijk-van Andel JF, Arts WFM, Barth PG, Loonen MCB (1990) Diagnostic features and clinical signs of 21 patients with lissencephaly type I. Dev Med Child Neurol 32: 707–717
Dieker H, Edwards RH, ZuRhein G, Chou SM, Hartman HA, Opitz JM (1969) The lissencephaly syndrome. Birth Defects 5: 53–64
Dobyns WB (1989) The neurogenetics of lissencephaly. Neurol Clin 7: 89–105
Dobyns WB, Stratton RF, Greenberg F (1984) Syndromes with lissencephaly. I. Miller-Dieker and Norman-Roberts syndromes and isolated lissencephaly. Am J Med Genet 18: 509–526
Dobyns WB, Gilbert EF, Opitz JM (1985) Further comments on the lissencephaly syndromes (Letter to the editor) Am J Med Genet 22:197–211
Dobyns WB, Kirkpatrick JB, Hittner HM, Roberts RM, Kretzer FL (1985) Syndromes with lissencephaly. II. Walker-Warburg and cerebro-oculo-muscular syndromes and a new syndrome with type II lissencephaly. Am J Med Genet 22:157–195
Dobyns WB, Pagon RA, Armstrong D, Curry CJR, Greenberg F, Grix A, Holmes RA, Laxova R, Michels VV, Robinow M, Zimmerman RL (1989) Diagnostic criteria for Walker-Warburg syndrome. Am J Med Genet 32:195–210
Dobyns WB, Curry CJR, Hoyme HE, Turlington L, Ledbetter DH (1991) Clinical and molecular diagnosis of Miller-Dieker syndrome. Am J Hum Genet 48:584–594
Dobyns WB, Elias ER, Newlin AC, Pagon RA, Ledbetter DH (1992) Causal heterogeneity in isolated lissencephaly. Neurology 42:1375–1388
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
Goertchen R (1975) Zur Pathologie der diffusen Pachygyrie. Zentralbl Allg Pathol 119:3–14
Gullotta F, Kuchelmeister K, Bückmann FW (1990) Agyrie-Bericht über 4 Fälle. In: Hanefeld F, Rating D, Christen HJ (eds) Aktuelle Neuropädiatrie 1989. Springer, Berlin Heidelberg New York, pp 73–77
Heggie P, Grossniklaus HE, Roessmann U, Chou SM, Cruse RP (1987) Cerebro-ocular dysplasia-muscular dystrophy syndrome. Report of two cases. Arch Opthalmol 105:520–524
Jellinger K, Rett A (1976) Agyria-pachygyria (lissencephaly syndrome). Neuropädiatrie 7:66–91
Kimura S, Kobayashi T, Sasaki Y, Hara M, Nishino T, Miyake S, Iwamoto H, Misugi N (1992) Congenital polyneuropathy in Walker-Warburg syndrome. Neuropediatrics 23:14–17
Korinthenberg R, Palm D, Schlake W, Klein J (1984) Congenital muscular dystrophy, brain malformation and ocular problems (muscle, eye and brain disease) in two German families. Eur J Pediatr 142:64–68
Krawinkel MB, Ernst M, Feller A, Flad HD, Mueller-Hermelink HK, Ulmer AJ, Schaub J (1989) Lissencephaly, abnormal lymph nodes, and T-cell deficiency in one patient. Am J Med Genet 33:436–443
Kuchelmeister K, Bergmann M, Gullotta F (1992) Lissencephalie-Spektrum der pathomorphologischen Befunde. Acta Histochem Suppl 42:251–255
Leyten QH, Renkawek K, Renier WO, Gabreëls FJM, Mooy CM, ter Laak HJ, Mullaart RA (1991) Neuropathological findings in muscle-eye-brain disease (MEB-D). Neuropathological delineation of MEB-D from congenital muscular dystrophy of the Fukuyama type. Acta Neuropathol 83:55–60
Miller G, Ladda RL, Towfighi J (1991) Cerebro-ocular dysplasia-muscular dystrophy (Walker-Warburg) syndrome. Findings in 20-week-old fetus. Acta Neuropathol 82:234–238
Miller JQ (1963) Lissencephaly in 2 siblings. Neurology 13:841–850
Norman MG, Roberts M, Sirois J, Tremblay LJM (1976) Lissencephaly. Can J Neurol Sci 3:39–46
Pavone L, Gullotta F, Grasso S, Vannuchi C (1986) Hydrocephalus, lissencephaly, ocular abnormalities and congenital muscular dystrophy. A Warburg syndrome variant? Neuropediatrics 17:206–211
Pavone L, Gullotta F, Incorpora G, Grasso S, Dobyns WB (1990) Isolated lissencephaly: report of four patients from two unrelated families. J Child Neurol 5:52–59
Santavuori P, Somer H, Sainio K, Rapola J, Kruus S, Nikitin T, Ketonen L, Leisti J (1989) Muscle-eye-brain disease (MEB). Brain Dev 11:147–153
Santavuori P, Pihko H, Sainio K, Lappi M, Somer H, Haltia M, Raitta C, Ketonen L, Leisti J (1990) Muscle-eye-brain disease and Walker-Warburg syndrome (Letter to the editor). Am J Med Genet 36:371–372
Stewart RM, Richman DP, Caviness VS Jr (1975) Lissencephaly and pachygyria. An architectonic and topographical analysis. Acta Neuropathol 31:1–12
Takada K, Becker LE, Takashima S (1987) Walker-Warburg syndrome with skeletal muscle involvement. A report of three patients. Pediatr Neurosci 13:202–209
Towfighi J, Sassani JW, Suzuki K, Ladda RL (1984) Cerebroocular dysplasia-muscular dystrophy (COD-MD) syndrome. Acta Neuropathol 65:110–123
Whitley CB, Thompson TR, Mastri AR, Gorlin RJ (1983) Warburg syndrome: lethal neurodysplasia with autosomal recessive inheritance. J Pediatr 102:547–551
Williams RS, Swisher CN, Jennings M, Ambler M, Caviness VS Jr (1984) Cerebro-ocular dysgenesis (Walker-Warburg syndrome): neuropathologic and etiologic analysis. Neurology 34:1531–1541
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kuchelmeister, K., Bergmann, M. & Gullotta, F. Neuropathology of lissencephalies. Child's Nerv Syst 9, 394–399 (1993). https://doi.org/10.1007/BF00306191
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00306191