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Lissencephaly 5(LIS5)

MedGen UID:
767571
Concept ID:
C3554657
Disease or Syndrome
Synonyms: LIS5
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
 
Gene (location): LAMB1 (7q31.1)
OMIM®: 615191
Orphanet: ORPHA352682

Definition

Lissencephaly-5 is an autosomal recessive brain malformation characterized by cobblestone changes in the cortex, more severe in the posterior region, and subcortical band heterotopia. Affected individuals have hydrocephalus, seizures, and severely delayed psychomotor development (summary by Radmanesh et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432). [from OMIM]

Clinical features

Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Occipital encephalocele
MedGen UID:
4935
Concept ID:
C0014067
Congenital Abnormality
A type of encephalocele (that is, a a protrusion of part of the cranial contents including brain tissue through a congenital opening in the cranium, typically covered with skin or mucous membrane) in the occipital region of the skull. Occipital encephalocele presents as a midline swelling over the occipital bone. It is usually covered with normal full-thickness scalp.
Seizure Disorders
MedGen UID:
4506
Concept ID:
C0014544
Disease or Syndrome
Epilepsy is a brain disorder that causes people to have recurring seizures. The seizures happen when clusters of nerve cells, or neurons, in the brain send out the wrong signals. People may have strange sensations and emotions or behave strangely. They may have violent muscle spasms or lose consciousness. Epilepsy has many possible causes, including illness, brain injury, and abnormal brain development. In many cases, the cause is unknown. Doctors use brain scans and other tests to diagnose epilepsy. It is important to start treatment right away. There is no cure for epilepsy, but medicines can control seizures for most people. When medicines are not working well, surgery or implanted devices such as vagus nerve stimulators may help. Special diets can help some children with epilepsy. NIH: National Institute of Neurological Disorders and Stroke.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Autosomal recessive nonsyndromic hydrocephalus is characterized by onset in utero of enlarged ventricles due to a disturbance of cerebrospinal fluid accumulation. Affected individuals may have neurologic impairment (summary by Drielsma et al., 2012). Hydrocephalus can also be caused by Arnold-Chiari malformation, atresia of foramen of Magendie, stenosis of aqueduct of Sylvius (307000), toxoplasmosis, hydranencephaly, etc. Furthermore, it develops in infancy or childhood in achondroplasia (100800) and in Hurler disease (607014). Genetic Heterogeneity of Congenital Hydrocephalus See also autosomal recessive HYC2 (615219), caused by mutation in the MPDZ gene (603785) on chromosome 9p. An X-linked form (307000) is caused by mutation in the L1CAM gene on (308840) on chromosome Xq28.
Congenital cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Underdevelopment of the cerebellum.
Gray matter heterotopias
MedGen UID:
452349
Concept ID:
C0266491
Finding
Gray matter heterotopia is a neurological disorder caused by clumps of grey matter being located in the wrong part of the brain. It is characterized as a type of cortical malformation. The neurons in heterotopia may appear to be normal, except for their mislocation; nuclear studies have shown glucose metabolism equal to that of normally positioned gray matter. The condition causes a variety of symptoms, but usually includes some degree of epilepsy or recurring seizures, and often affects the brain's ability to function on higher levels. Symptoms range from nonexistent to profound, in which case heterotopia can result in severe seizure disorder, loss of motor skills, and mental retardation.
Type II lissencephaly
MedGen UID:
96562
Concept ID:
C0431376
Congenital Abnormality
The smooth pebbled appearance of the CEREBRAL CORTEX with a thickened cortex and reduced and abnormal white matter, which results from migration of heterotopic neurons beyond the marginal zone into the leptomeninges through gaps in the external BASEMENT MEMBRANE. There is also enlarged ventricles, underdeveloped BRAINSTEM and cerebellum, and absence of the CORPUS CALLOSUM. These abnormalities occur as a syndrome without other birth defects (cobblestone complex) or in other syndromes associated with congenital MUSCULAR DYSTROPHY, often involving the eye, such as the Walker-Warburg Syndrome, Fukuyama congenital muscular dystrophy, and muscle-eye-brain disease.
Abnormality of the cerebral white matter
MedGen UID:
181756
Concept ID:
C0948163
Pathologic Function
Non-specific white matter changes in the BRAIN, often seen after age 65. Changes include loss of AXONS; MYELIN pallor, GLIOSIS, loss of ependymal cells, and enlarged perivascular spaces. Leukoaraiosis is a risk factor for DEMENTIA and CEREBROVASCULAR DISORDERS.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Hypoplasia of the brainstem
MedGen UID:
334226
Concept ID:
C1842688
Finding
Underdevelopment of the brainstem.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.
Occipital encephalocele
MedGen UID:
4935
Concept ID:
C0014067
Congenital Abnormality
A type of encephalocele (that is, a a protrusion of part of the cranial contents including brain tissue through a congenital opening in the cranium, typically covered with skin or mucous membrane) in the occipital region of the skull. Occipital encephalocele presents as a midline swelling over the occipital bone. It is usually covered with normal full-thickness scalp.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Macrocephaly refers to an abnormally enlarged head inclusive of the scalp, cranial bones, and intracranial contents. Macrocephaly may be due to megalencephaly (true enlargement of the brain parenchyma), and the 2 terms are often used interchangeably in the genetic literature (reviews by Olney, 2007 and Williams et al., 2008). Autosomal recessive macrocephaly/megalencephaly syndrome is characterized by an enlarged cranium apparent at birth or in early childhood. Affected individuals have intellectual disability and may have dysmorphic facial features resulting from the macrocephaly (summary by Alfaiz et al., 2014).
Occipital encephalocele
MedGen UID:
4935
Concept ID:
C0014067
Congenital Abnormality
A type of encephalocele (that is, a a protrusion of part of the cranial contents including brain tissue through a congenital opening in the cranium, typically covered with skin or mucous membrane) in the occipital region of the skull. Occipital encephalocele presents as a midline swelling over the occipital bone. It is usually covered with normal full-thickness scalp.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Macrocephaly refers to an abnormally enlarged head inclusive of the scalp, cranial bones, and intracranial contents. Macrocephaly may be due to megalencephaly (true enlargement of the brain parenchyma), and the 2 terms are often used interchangeably in the genetic literature (reviews by Olney, 2007 and Williams et al., 2008). Autosomal recessive macrocephaly/megalencephaly syndrome is characterized by an enlarged cranium apparent at birth or in early childhood. Affected individuals have intellectual disability and may have dysmorphic facial features resulting from the macrocephaly (summary by Alfaiz et al., 2014).

Recent clinical studies

Etiology

Di Donato N, Jean YY, Maga AM, Krewson BD, Shupp AB, Avrutsky MI, Roy A, Collins S, Olds C, Willert RA, Czaja AM, Johnson R, Stover JA, Gottlieb S, Bartholdi D, Rauch A, Goldstein A, Boyd-Kyle V, Aldinger KA, Mirzaa GM, Nissen A, Brigatti KW, Puffenberger EG, Millen KJ, Strauss KA, Dobyns WB, Troy CM, Jinks RN
Am J Hum Genet 2016 Nov 3;99(5):1117-1129. Epub 2016 Oct 20 doi: 10.1016/j.ajhg.2016.09.010. PMID: 27773430Free PMC Article
Tsai MH, Kuo PW, Myers CT, Li SW, Lin WC, Fu TY, Chang HY, Mefford HC, Chang YC, Tsai JW
Eur J Paediatr Neurol 2016 Sep;20(5):788-94. Epub 2016 May 30 doi: 10.1016/j.ejpn.2016.05.010. PMID: 27292316
Magen D, Ofir A, Berger L, Goldsher D, Eran A, Katib N, Nijem Y, Vlodavsky E, Tzur S, Behar DM, Fellig Y, Mandel H
Hum Genet 2015 Mar;134(3):305-14. Epub 2015 Jan 6 doi: 10.1007/s00439-014-1522-5. PMID: 25560765
de Wit MC, de Rijk-van Andel J, Halley DJ, Poddighe PJ, Arts WF, de Coo IF, Mancini GM
Dev Med Child Neurol 2011 May;53(5):417-21. Epub 2011 Mar 17 doi: 10.1111/j.1469-8749.2011.03937.x. PMID: 21410694
Leger PL, Souville I, Boddaert N, Elie C, Pinard JM, Plouin P, Moutard ML, des Portes V, Van Esch H, Joriot S, Renard JL, Chelly J, Francis F, Beldjord C, Bahi-Buisson N
Neurogenetics 2008 Oct;9(4):277-85. Epub 2008 Aug 7 doi: 10.1007/s10048-008-0141-5. PMID: 18685874

Diagnosis

Syed AE
BMJ Case Rep 2015 Jan 22;2015 doi: 10.1136/bcr-2014-206522. PMID: 25612753Free PMC Article
Mulder TJ, Niyazov DM, Kattash MM, Longo SA, Robichaux Iii AG, Snyder CS
Congenit Heart Dis 2010 Sep-Oct;5(5):486-90. doi: 10.1111/j.1747-0803.2010.00390.x. PMID: 21087439
Saillour Y, Carion N, Quelin C, Leger PL, Boddaert N, Elie C, Toutain A, Mercier S, Barthez MA, Milh M, Joriot S, des Portes V, Philip N, Broglin D, Roubertie A, Pitelet G, Moutard ML, Pinard JM, Cances C, Kaminska A, Chelly J, Beldjord C, Bahi-Buisson N
Arch Neurol 2009 Aug;66(8):1007-15. doi: 10.1001/archneurol.2009.149. PMID: 19667223
Morris-Rosendahl DJ, Najm J, Lachmeijer AM, Sztriha L, Martins M, Kuechler A, Haug V, Zeschnigk C, Martin P, Santos M, Vasconcelos C, Omran H, Kraus U, Van der Knaap MS, Schuierer G, Kutsche K, Uyanik G
Clin Genet 2008 Nov;74(5):425-33. doi: 10.1111/j.1399-0004.2008.01093.x. PMID: 18954413
Mei D, Lewis R, Parrini E, Lazarou LP, Marini C, Pilz DT, Guerrini R
J Med Genet 2008 Jun;45(6):355-61. Epub 2008 Feb 19 doi: 10.1136/jmg.2007.056507. PMID: 18285425

Therapy

Kayyali HR, Gustafson M, Myers T, Thompson L, Williams M, Abdelmoity A
Pediatr Neurol 2014 Mar;50(3):224-7. Epub 2013 Dec 4 doi: 10.1016/j.pediatrneurol.2013.11.021. PMID: 24433856
Toba S, Tamura Y, Kumamoto K, Yamada M, Takao K, Hattori S, Miyakawa T, Kataoka Y, Azuma M, Hayasaka K, Amamoto M, Tominaga K, Wynshaw-Boris A, Wanibuchi H, Oka Y, Sato M, Kato M, Hirotsune S
Sci Rep 2013;3:1224. Epub 2013 Feb 6 doi: 10.1038/srep01224. PMID: 23390575Free PMC Article
Kobayashi K, Mimaki N, Endoh F, Inoue T, Yoshinaga H, Ohtsuka Y
Epilepsy Res 2011 Oct;96(3):276-82. Epub 2011 Jul 28 doi: 10.1016/j.eplepsyres.2011.06.012. PMID: 21802260
Wang SB, Weng WC, Fan PC, Lee WT
Pediatr Neurol 2008 Aug;39(2):85-90. doi: 10.1016/j.pediatrneurol.2008.04.007. PMID: 18639750
Mori K, Hashimoto T, Tayama M, Miyazaki M, Fukuda K, Endo S, Kuroda Y
Brain Dev 1994 Sep-Oct;16(5):365-73. PMID: 7892955

Prognosis

Bahi-Buisson N, Souville I, Fourniol FJ, Toussaint A, Moores CA, Houdusse A, Lemaitre JY, Poirier K, Khalaf-Nazzal R, Hully M, Leger PL, Elie C, Boddaert N, Beldjord C, Chelly J, Francis F; SBH-LIS European Consortium.
Brain 2013 Jan;136(Pt 1):223-44. doi: 10.1093/brain/aws323. PMID: 23365099Free PMC Article
de Wit MC, de Rijk-van Andel J, Halley DJ, Poddighe PJ, Arts WF, de Coo IF, Mancini GM
Dev Med Child Neurol 2011 May;53(5):417-21. Epub 2011 Mar 17 doi: 10.1111/j.1469-8749.2011.03937.x. PMID: 21410694
Mulder TJ, Niyazov DM, Kattash MM, Longo SA, Robichaux Iii AG, Snyder CS
Congenit Heart Dis 2010 Sep-Oct;5(5):486-90. doi: 10.1111/j.1747-0803.2010.00390.x. PMID: 21087439
Saillour Y, Carion N, Quelin C, Leger PL, Boddaert N, Elie C, Toutain A, Mercier S, Barthez MA, Milh M, Joriot S, des Portes V, Philip N, Broglin D, Roubertie A, Pitelet G, Moutard ML, Pinard JM, Cances C, Kaminska A, Chelly J, Beldjord C, Bahi-Buisson N
Arch Neurol 2009 Aug;66(8):1007-15. doi: 10.1001/archneurol.2009.149. PMID: 19667223
Leger PL, Souville I, Boddaert N, Elie C, Pinard JM, Plouin P, Moutard ML, des Portes V, Van Esch H, Joriot S, Renard JL, Chelly J, Francis F, Beldjord C, Bahi-Buisson N
Neurogenetics 2008 Oct;9(4):277-85. Epub 2008 Aug 7 doi: 10.1007/s10048-008-0141-5. PMID: 18685874

Clinical prediction guides

Bahi-Buisson N, Souville I, Fourniol FJ, Toussaint A, Moores CA, Houdusse A, Lemaitre JY, Poirier K, Khalaf-Nazzal R, Hully M, Leger PL, Elie C, Boddaert N, Beldjord C, Chelly J, Francis F; SBH-LIS European Consortium.
Brain 2013 Jan;136(Pt 1):223-44. doi: 10.1093/brain/aws323. PMID: 23365099Free PMC Article
Devisme L, Bouchet C, Gonzalès M, Alanio E, Bazin A, Bessières B, Bigi N, Blanchet P, Bonneau D, Bonnières M, Bucourt M, Carles D, Clarisse B, Delahaye S, Fallet-Bianco C, Figarella-Branger D, Gaillard D, Gasser B, Delezoide AL, Guimiot F, Joubert M, Laurent N, Laquerrière A, Liprandi A, Loget P, Marcorelles P, Martinovic J, Menez F, Patrier S, Pelluard F, Perez MJ, Rouleau C, Triau S, Attié-Bitach T, Vuillaumier-Barrot S, Seta N, Encha-Razavi F
Brain 2012 Feb;135(Pt 2):469-82. Epub 2012 Feb 9 doi: 10.1093/brain/awr357. PMID: 22323514
de Wit MC, de Rijk-van Andel J, Halley DJ, Poddighe PJ, Arts WF, de Coo IF, Mancini GM
Dev Med Child Neurol 2011 May;53(5):417-21. Epub 2011 Mar 17 doi: 10.1111/j.1469-8749.2011.03937.x. PMID: 21410694
Saillour Y, Carion N, Quelin C, Leger PL, Boddaert N, Elie C, Toutain A, Mercier S, Barthez MA, Milh M, Joriot S, des Portes V, Philip N, Broglin D, Roubertie A, Pitelet G, Moutard ML, Pinard JM, Cances C, Kaminska A, Chelly J, Beldjord C, Bahi-Buisson N
Arch Neurol 2009 Aug;66(8):1007-15. doi: 10.1001/archneurol.2009.149. PMID: 19667223
Leger PL, Souville I, Boddaert N, Elie C, Pinard JM, Plouin P, Moutard ML, des Portes V, Van Esch H, Joriot S, Renard JL, Chelly J, Francis F, Beldjord C, Bahi-Buisson N
Neurogenetics 2008 Oct;9(4):277-85. Epub 2008 Aug 7 doi: 10.1007/s10048-008-0141-5. PMID: 18685874

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