Familial lissencephaly with cleft palate and severe cerebellar hypoplasia
Berit Kerner
Medical Genetics Birth Defects Center, Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, SHARE's Child Disability Center, UCLA University Affiliated Program, International Skeletal Dysplasia Registry, UCLA School of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
Search for more papers by this authorCorresponding Author
John M. Graham Jr.
Medical Genetics Birth Defects Center, Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, SHARE's Child Disability Center, UCLA University Affiliated Program, International Skeletal Dysplasia Registry, UCLA School of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
Director of Clinical Genetics and Dysmorphology, Cedars-Sinai Medical Center, 444 South San Vicente Blvd. #1001, Los Angeles, CA 90048Search for more papers by this authorJeffrey A. Golden
Department of Pathology, Children's Hospital of Pennsylvania and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Search for more papers by this authorSamuel H. Pepkowitz
Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California
Search for more papers by this authorWilliam B. Dobyns
Department of Human Genetics, University of Chicago, Chicago, Illinois
Search for more papers by this authorBerit Kerner
Medical Genetics Birth Defects Center, Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, SHARE's Child Disability Center, UCLA University Affiliated Program, International Skeletal Dysplasia Registry, UCLA School of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
Search for more papers by this authorCorresponding Author
John M. Graham Jr.
Medical Genetics Birth Defects Center, Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, SHARE's Child Disability Center, UCLA University Affiliated Program, International Skeletal Dysplasia Registry, UCLA School of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
Director of Clinical Genetics and Dysmorphology, Cedars-Sinai Medical Center, 444 South San Vicente Blvd. #1001, Los Angeles, CA 90048Search for more papers by this authorJeffrey A. Golden
Department of Pathology, Children's Hospital of Pennsylvania and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Search for more papers by this authorSamuel H. Pepkowitz
Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California
Search for more papers by this authorWilliam B. Dobyns
Department of Human Genetics, University of Chicago, Chicago, Illinois
Search for more papers by this authorAbstract
Lissencephaly is a brain malformation characterized by absence of gyral formation, resulting in a smooth brain surface. Histologic study shows severe anomalies of cerebral cortical development. Several lissencephaly syndromes have been described. Here we report a familial syndrome of lissencephaly, cleft palate, diffuse agyria, and severe cerebellar hypoplasia. Microscopic examination of the abnormally thick cerebral cortex showed absence of cortical layering, with preservation of the pia-glial barrier. This is the first report of recurrent lissencephaly with cleft palate and severe cerebellar hypoplasia in which these unique neuropathology findings are described. Autosomal recessive inheritance is suggested by recurrence in sibs within the same family, but germ cell mosaicism for a dominant mutation is not excluded. Am. J. Med. Genet. 87:440–445, 1999. © 1999 Wiley-Liss, Inc.
REFERENCES
- Barth PG, Mullaart R, Stam FC, Slooff JL. 1982. Familial lissencephaly with extreme neopallial hypoplasia. Brain Dev 4: 145–151.
- Berg MJ, Schifitto G, Powers JM, Martinez-Capolino C, Fong CT, Myers GJ, Epstein LG, Walsh CA. 1998. X-linked female band heterotopiamale lissencephaly syndrome. Neurology 50: 1143–1146.
- Clark GD, McNeil RS, Bix GJ, Swarm JW. 1995. Platelet-activating factor produces neuronal growth cone collapse. Neuro Report 6: 2569–2575.
- des Portes V, Pinard JM, Billuart P, Vinet MC, Koulakoff A, Carrie A, Gelot A, Dupuis E, Motte J, Berwald-Netter Y, Catala M, Kahn A, Beldjord C, Chelly J. 1998. A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome. Cell 92: 51–61.
- Dobyns WB, Andermann E, Andermann F, Czapansky-Beilman D, Dubeau F, Dulac O, Guerrini R, Hirsch B, Ledbetter DH, Lee NS, Motte J, Pinard JM, Radtke RA, Ross ME, Tampieri D, Walsh CA, Truwit CL. 1996. X-linked malformations of neuronal migration. Neurology 47: 331–339.
- Dobyns WB, Elias ER, Newlin AC, Pagon RA, Ledbetter DH. 1992. Causal heterogeneity in isolated lissencephaly. Neurology 42: 1375–1388.
- Dobyns WB, Reiner O, Carrozzo R, Ledbetter DH. 1993. Lissencephaly. A human brain malformation associated with deletion of the LIS1 gene located at chromosome 17p13. JAMA 270: 2838–2842.
- Dobyns WB, Truwit CL. 1995. Lissencephaly and other malformations of cortical development: 1995 update. Neuropediatrics 26: 132–147.
- Farah S, Sabry MA, Khuraibet A, Khaffagi S, Rudwan M, Hassan M, Haseeb N, Abulhassan S, Abdel-Rasool MA, Elgamal S, Qasrawi B, Al-Busairi W, Farag TI. 1997. Lissencephaly associated with cerebellar hypoplasia and myoclonic epilepsy in a Bedouin kindred: a new syndrome? Clin Genet 51: 326–330.
- Gleeson JG, Allen KM, Fox JW, Lamperti ED, Berkovic S, Scheffer I, Cooper EC, Dobyns WB, Minnerath SR, Ross ME, Walsh CA. 1998. Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell 92: 63–72.
- Hattori M, Adachi H, Tsujimoto M, Arai H, Inoue K. 1994. Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor. Nature 370: 216–218.
- Hirotsune S, Fleck MW, Gambello MJ, Bix GJ, Chen A, Clark GD, Ledbetter DH, McBain CJ, Wynshaw-Boris A. 1998. Graded reduction of Pafah1b1 (Lis1) activity results in neuronal migration defects and early embryonic lethality. Nature Genetics 19: 333–339.
- Jouet M, Rosenthal A, Armstrong G, MacFarlane J, Stevenson R, Paterson J, Metzenberg A, lonasescu V, Temple K, Kenwrick S. 1994. X-linked spastic paraplegia (SPG1), MASA syndrome, and X-linked hydrocephalus result from mutations in the L1 gene. Nature Genetics 7: 402–407.
- Kornecki E, Ehrlich YH. 1988. Neuroregulatory and neuropathological action of the ether-phospholipid platelet-activating factor. Science 240: 1792–1794.
- Kroon AA, Smit BJ, Barth PG, Hennekam RCM. 1996. Lissencephaly with extreme cerebral and cerebellar hypoplasia. A magnetic resonance imaging study. Neuropediatrics 27: 273–276.
- Lo Nigro C, Chong CS, Smith AC, Dobyns WB, Carrozzo R, Ledbetter DH. 1997. Point mutations and an intragenic deletion in LIS1, the lissencephaly causative gene in isolated lissencephaly sequence and Miller-Dieker syndrome. Hum Mol Genet 6: 157–164.
- McConnell S. 1995. Constructing the cerebral cortex: neurogenesis and fate determination. Neuron 15: 761–768.
- Pearlman AL, Faust PL, Hatten ME, Brunstrom JE. 1998. New directions for neuronal migration. Curr Opin Neurobiol 8: 45–54.
- Rakic P. 1990. Principles of neural cell migration. Experientia 46: 882–891.
- Rakic P, Cameron R, Komuro H. 1994. Recognition, adhesion, transmembrane signaling, and cell motility in guided neuronal migration. Curr Opin Neurobiol 4: 63–69.
- Reiner O, Carrozzo R, Shen Y, Wehnert M, Faustinella F, Dobyns WB, Caskey CT, Ledbetter DH. 1993. Isolation of a Miller-Dieker lissencephaly gene containing G protein β subunit-like repeats. Nature 364: 717–721.
- Sapir T, Elbaum M, Reiner O. 1997. Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit. Embo J 16: 6977–6984.
- Sidman R, Rakic P. 1973. Neuronal migration, with special reference to developing human brain: a review. Brain Research 62: 1–35.
- Sossey-Alaoui K, Hartung AJ, Guerrini R, Manchester DK, Posar A, Puche-Mira A, Andermann E, Dobyns WB, Srivastava AK. 1998. Human doublecortin (DCX) and the homologous gene in mouse encode a putative Ca2+ dependent signaling protein which is mutated in human X-linked neuronal migration defects. Hum Mol Genet 7: 1327–1332.
- Squier MV. 1993. Development of the cortical dysplasia of type II lissencephaly. Neuropathology and Applied Neurobiology 19: 209–213.
