CLINICAL CASE OF CONGENITAL ANOMALIES OF NEURON MIGRATION
Keywords:
congenital cortical defect, lissencephaly, children, epilepsy.Abstract
Introduction. Lissencephaly (LIS), which includes the terms agyria and pachygyria), together with heterotopy of subcortical bands (SBH), includes a spectrum of cortical malformations caused by insufficient migration of neurons. In lyssencephaly, an abnormally thick cortex with reduced or absent formation of cerebral gyri is detected, and heterothopia of subcortical bands is a cluster of neurons along the normal cortex.
The purpose of this publication is to focus the attention of neurologists on global delays in neuropsychic development in combination with severe epileptic syndromes in children with heterotopias of the cortex (disorders of neuronal migration and the formation of cytoarchitectonics of the cortex) with a description of their own clinical observation.
Material and methods. In our observation of 1 girl, at the age of 4.5 months, there is a malformation resulting from abnormal neuronal migration, with lyssencephaly and pachygyria in the form of subcortical broad ribbon heterotopia. The diagnosis was confirmed by an MRI examination of the brain in the 1.5 Tesla mode.
Results. The girl has diffuse heterotopia of the cortex, in the form of a wide strip of double cortex in the area where the subcortical white matter is usually located. The zone of the "second cortex" on MRI (hyperdense signal in T-1 and T-2 modes) is wider than the normally located cortex and is visualized in all lobes of the brain (frontal, parietal, temporal and occipital). The clinical and neuroimaging picture made it possible to make a clinical diagnosis: Symptomatic epilepsy with myoclonic and clonic generalized seizures, a period of stabilization of seizures, delayed motor and pre-speech development, congenital anomaly of neuronal migration (ribbon-like heterotopia of gray matter of both hemispheres), pachygyria.
Conclusion. Thus, in combination, lyssencephaly with pachygyria represent an extremely heterogeneous group of diseases with congenital anomalies of the development of the cerebral cortex, which is often manifested by drug-resistant epilepsy, as well as neurological and intellectual disabilities. There are still no effective protocols for the treatment and management of these patients, which is due to incomplete studies of phenotype-genotype correlations. But the main problems of such children are resistance to anticovulsant therapy, mental retardation and motor disorders against the background of spasticity. In the future, it is necessary to create a clinical registry for patients with LIS, as well as conduct research to improve the quality of life of patients.
References
1. Dobyns WB, Guerrini R, Leventer RJ. Malformations of Cortical Development. In: Swaiman KF, Ashwal S, Ferriero DM, Schor NF, editors. Swaiman’s Pediatric Neurology: Principles and Practice. 5. Edinburgh: Elsevier Saunders; 2012. pp. 202–231.
2. Forman MS, Squier W, Dobyns WB, Golden JA. Genotypically defined lissencephalies show distinct pathologies. J Neuropathol Exp Neurol. 2005;64:847–857.
3. Barkovich AJ, Kuzniecky RI, Jackson GD, Guerrini R, Dobyns. A developmental and genetic classification for malformations of cortical development. Neurology. 2005;65:1873-1887. doi: 10.1212/01.wnl.0000183747.05269.2d]
4. Barkovich AJ, Kuzniecky RI, Jackson GD, Guerrini R, Dobyns WB. Classification system for malformations of cortical development, update 2001. Neurology. 2001;57:2168-2178. doi: 10.1212/wnl.57.12.2168
5. Di Donato N, Chiari S, Mirzaa GM, Aldinger K, Parrini E, Olds C, Barkovich AJ, Guerrini R, Dobyns WB. Lissencephaly: Expanded imaging and clinical classification. Am J Med Genet A. 2017 Jun;173(6):1473-1488. doi: 10.1002/ajmg.a.38245. Epub 2017 Apr 25. PMID: 28440899; PMCID: PMC5526446
6. Stratton RF, Dobyns WB, Airhart SD, Ledbetter DH. New chromosomal syndrome: Miller-Dieker syndrome and monosomy 17p13. Hum Genet. 1984;67(2):193-200. doi: 10.1007/BF00273000. PMID: 6745939
7. Abdollahi MR, Morrison E, Sirey T, Molnar Z, Hayward BE, Carr IM, Springell K, Woods CG, Ahmed M, Hattingh L, Corry P, Pilz DT, Stoodley N, Crow Y, Taylor GR, Bonthron DT, Sheridan E. Mutation of the variant alpha-tubulin TUBA8 results in polymicrogyria with optic nerve hypoplasia. Am J Hum Genet. 2009;85:737–744. doi: 10.1016/j.ajhg.2009.10.007
8. Boycott KM, Bonnemann C, Herz J, Neuert S, Beaulieu C, Scott JN, Venkatasubramanian A, Parboosingh JS. Mutations in VLDLR as a cause for autosomal recessive cerebellar ataxia with mental retardation (dysequilibrium syndrome). J Child Neurol. 2009 Oct;24(10):1310-5. doi: 10.1177/0883073809332696. Epub 2009 Mar 30. PMID: 19332571; PMCID: PMC2849979
9. Breuss M, Heng JI, Poirier K, Tian G, Jaglin XH, Qu Z, Braun A, Gstrein T, Ngo L, Haas M, Bahi-Buisson N, Moutard ML, Passemard S, Verloes A, Gressens P, Xie Y, Robson KJ, Rani DS, Thangaraj K, Clausen T, Chelly J, Cowan NJ, Keays DA. Mutations in the β-tubulin gene TUBB5 cause microcephaly with structural brain abnormalities. Cell Rep. 2012 Dec 27;2(6):1554-62. doi: 10.1016/j.celrep.2012.11.017. Epub 2012 Dec 13. PMID: 23246003; PMCID: PMC3595605.
10. 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. Mutations in CRADD Result in Reduced Caspase-2-Mediated Neuronal Apoptosis and Cause Megalencephaly with a Rare Lissencephaly Variant. Am J Hum Genet. 2016 Nov 3;99(5):1117-1129. doi: 10.1016/j.ajhg.2016.09.010. Epub 2016 Oct 20. PMID: 27773430; PMCID: PMC5097945
11. Gleeson JG, Allen KM, Fox JW, Lamperti ED, Berkovic S, Scheffer I, Cooper EC, Dobyns WB, Minnerath SR, Ross ME, Walsh CA. Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell. 1998 Jan 9;92(1):63-72. doi: 10.1016/s0092-8674(00)80899-5. PMID: 9489700
12. Riviere JB, van Bon BW, Hoischen A, Kholmanskikh SS, O’Roak BJ, Gilissen C, Gijsen S, Sullivan CT, Christian SL, Abdul-Rahman OA, Atkin JF, Chassaing N, Drouin-Garraud V, Fry AE, Fryns JP, Gripp KW, Kempers M, Kleefstra T, Mancini GM, Nowaczyk MJ, van Ravenswaaij-Arts CM, Roscioli T, Marble M, Rosenfeld JA, Siu VM, de Vries BB, Shendure J, Verloes A, Veltman JA, Brunner HG, Ross ME, Pilz DT, Dobyns WB. De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. Nat Genet. 2012;44(4):440–444. S441–442. doi: 10.1038/ng.1091. PMID: 22366783 PMCID: PMC3677859
13. Willemsen MH, Vissers LE, Willemsen MA, van Bon BW, Kroes T, de Ligt J, de Vries BB, Schoots J, Lugtenberg D, Hamel BC, van Bokhoven H, Brunner HG, Veltman JA, Kleefstra T. Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects. J Med Genet. 2012;49(3):179–183. doi: 10.1136/jmedgenet-2011-100542. PMID: 22368300
14. Kolbjer S, Martin DA, Pettersson M, Dahlin M, Anderlid BM. Lissencephaly in an epilepsy cohort: Molecular, radiological and clinical aspects. Eur J Paediatr Neurol. 2021 Jan;30:71-81. doi: 10.1016/j.ejpn.2020.12.011. Epub 2021 Jan 8. PMID: 33453472
15. Romaniello R, Arrigoni F, Fry AE, Bassi MT, Rees MI, Borgatti R, Pilz DT, Cushion TD. Tubulin genes and malformations of cortical development. Eur J Med Genet. 2018 Dec;61(12):744-754. doi: 10.1016/j.ejmg.2018.07.012. Epub 2018 Jul 17. PMID: 30016746.
16. Haverfield EV, Whited AJ, Petras KS, Dobyns WB, Das S. Intragenic deletions and duplications of the LIS1 and DCX genes: a major disease-causing mechanism in lissencephaly and subcortical band heterotopia. Eur J Hum Genet. 2009 Jul;17(7):911-8. doi: 10.1038/ejhg.2008.213. Epub 2008 Dec 3. PMID: 19050731; PMCID: PMC2986498
17. NIH, National Library of Medicine, Medlineplus, DCX gene, 2018 Available from: https://medlineplus.gov/genetics/gene/dcx/#conditions
18. Koenig M, Dobyns WB, Di Donato N. Lissencephaly: Update on diagnostics and clinical management. Eur J Paediatr Neurol. 2021 Nov;35:147-152. doi: 10.1016/j.ejpn.2021.09.013. Epub 2021 Oct 7. PMID: 34731701
19. Herbst SM, Proepper CR, Geis T, Borggraefe I, Hahn A, Debus O, Haeussler M, von Gersdorff G, Kurlemann G, Ensslen M, Beaud N, Budde J, Gilbert M, Heiming R, Morgner R, Philippi H, Ross S, Strobl-Wildemann G, Muelleder K, Vosschulte P, Morris-Rosendahl DJ, Schuierer G, Hehr U. LIS1-associated classic lissencephaly: A retrospective, multicenter survey of the epileptogenic phenotype and response to antiepileptic drugs. Brain Dev. 2016 Apr;38(4):399-406. doi: 10.1016/j.braindev.2015.10.001. Epub 2015 Oct 19. PMID: 26494205
20. Kolbjer S, Martin DA, Pettersson M, Dahlin M, Anderlid BM. Lissencephaly in an epilepsy cohort: Molecular, radiological and clinical aspects. Eur J Paediatr Neurol. 2021 Jan;30:71-81. doi: 10.1016/j.ejpn.2020.12.011. Epub 2021 Jan 8. PMID: 33453472
