Donald School Journal of Ultrasound in Obstetrics and Gynecology

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VOLUME 15 , ISSUE 2 ( April-June, 2021 ) > List of Articles


Neurosonographic Approach to Malformations of Cortical Development

Ritsuko K Pooh, Nana Matsuzawa, Megumi Machida, Takako Nakamura, Hideaki Chiyo

Keywords : Fetus, Brain, Cortical development, Malformation, Proliferation, Migration, 3D ultrasound, Neurosonography, Imaging

Citation Information : Pooh RK, Matsuzawa N, Machida M, Nakamura T, Chiyo H. Neurosonographic Approach to Malformations of Cortical Development. Donald School J Ultrasound Obstet Gynecol 2021; 15 (2):179-187.

DOI: 10.5005/jp-journals-10009-1699

License: CC BY-NC 4.0

Published Online: 02-07-2021

Copyright Statement:  Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.


Malformations of cortical development (MCD) are disorders of cerebral cortex formation caused by various genetic mutations, infections, vascular abnormalities, or metabolic abnormalities. Malformations of cortical development are associated with abnormal cortical structure, ectopic gray matter, and odd brain size. It is hard to depict cortical development and its disorder by ultrasonography during the fetal period. The phenotype of cortical development does not appear until 8 months of gestation when gyrus/sulcus formation becomes apparent. Early detection of impaired cell migration and cortical maldevelopment is a challenge in the field of prenatal fetal neuroimaging. However, longitudinal neuroimaging throughout the embryological and fetal period, combined with the precise genetic investigation, fetal MCD has been diagnosed due to the development of neuroimaging and the remarkable development of the next-generation sequencing. Perhaps shortly, fetal MCD diagnosis will be possible more accurately and earlier. The combination of molecular genetics and detailed neurosonography has established “Neurosonogenetics”, a new field in multidisciplinary prenatal neurology, for prompt prenatal/postnatal management, care, prevention, and treatment in fetal and pediatric neurology.

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  1. Raybaud C, Widjaja E. Development and dysgenesis of the cerebral cortex: malformations of cortical development. Neuroimaging Clin N Am 2011;21(3):483–543. DOI: 10.1016/j.nic.2011.05.014.
  2. Guerrini R, Dobyns WB. Malformations of cortical development: clinical features and genetic causes. Lancet Neurol 2014;13(7):710–726. DOI: 10.1016/S1474-4422(14)70040-7.Malformations.
  3. Barkovich AJ, Guerrini R, Kuzniecky RI, et al. A developmental and genetic classification for malformations of cortical development: update 2012. Brain 2012;135(5):1348–1369. DOI: 10.1093/brain/aws019.
  4. Pasquier B, Péoc'h M, Fabre-Bocquentin B, et al. Surgical pathology of drug-resistant partial epilepsy. A 10-year-experience with a series of 327 consecutive resections. Epileptic Disord 2002;4(2):99–119.
  5. Severino M, Geraldo AF, Utz N, et al. Definitions and classification of malformations of cortical development: practical guidelines. Brain 2020;143(10):2874–2894. DOI: 10.1093/brain/awaa174.
  6. Desikan RS, Barkovich AJ. Malformations of cortical development. Ann Neurol 2016;80(6):797–810. DOI: 10.1002/ana.24793.
  7. Woods CG, Parker A. Investigating microcephaly. Arch Dis Child 2013;98(9):707–713. DOI: 10.1136/archdischild-2012-302882.
  8. Ashwal S, Michelson D, Plawner L, et al. Practice parameter: diagnostic assessment of the child with report of the quality standards subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2009;73(11):887–897. DOI: 10.1212/WNL.0b013e3181b783f7.
  9. Guernsey DL, Jiang H, Hussin J, et al. Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4. Am J Hum Genet 2010;87(1):40–51. DOI: 10.1016/j.ajhg.2010.06.003Published online.
  10. Manzini MC, Walsh CA. The genetics of brain malformations. Genet Neurodevelop Disord 2015(5). DOI: 10.1002/9781118524947.ch7.
  11. Brunk K, Vernay B, Griffith E, et al. Microcephalin coordinates mitosis in the syncytial drosophila embryo. J Cell Sci. 2007;120(Pt 20):3578–3588. DOI: 10.1242/jcs.014290Published online.
  12. Trimborn M, Bell SM, Felix C, et al. Mutations in microcephalin cause aberrant regulation of chromosome condensation. Am J Hum Genet. 2004;75(2):261–266. DOI: 10.1086/422855Published online.
  13. Edwards TJ, Sherr EH, Barkovich AJ, et al. Clinical, genetic and imaging findings identify new causes for corpus callosum development syndromes. Brain 2014;137(Pt 6):1579–1613. DOI: 10.1093/brain/awt358Published online.
  14. Bond J, Roberts E, Springell K, et al. A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size. Nat Genet 2005;37(4):353–355. DOI: 10.1038/ng1539Published online.
  15. Kumar A, Girimaji SC, Duvvari MR, et al. Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly. Am J Hum Genet. 2009;84(2):286–290. DOI: 10.1016/j.ajhg.2009.01.017Published online.
  16. Squier W, Jansen A. Polymicrogyria: pathology, fetal origins and mechanisms. Acta Neuropathol Commun 2014;2(1):1–16. DOI: 10.1186/s40478-014-0080-3.
  17. Mirzaa GM, Poduri A. Megalencephaly and hemimegalencephaly: breakthroughs in molecular etiology. Am J Med Genet Part C Semin Med Genet. 2014;166(2):156–172. DOI: 10.1002/ajmg.c. 31401.
  18. Keppler-Noreuil KM, Rios JJ, Parker VER, et al. PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. Am J Med Genet Part A 2015;167(2):287–295. DOI: 10.1002/ajmg.a.36836.
  19. Mirzaa GM, Rivière JB, Dobyns WB. Megalencephaly syndromes and activating mutations in the PI3K-AKT pathway: MPPH and MCAP. Am J Med Genet Part C Semin Med Genet. 2013;163C(2):122–130. DOI: 10.1002/ajmg.c.31361Published online.
  20. Jansen LA, Mirzaa GM, Ishak GE, et al. PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia. Brain 2015;138(6):1613–1628. DOI: 10.1093/brain/awv045.
  21. Blümcke I, Thom M, Aronica E, et al. The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc task force of the ILAE diagnostic methods commission. Epilepsia 2011;52(1):158–174. DOI: 10.1111/j.1528-1167.2010.02777.x.
  22. Northrup H, Krueger DA. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 international tuberous sclerosis complex consensus conference. Pediatr Neurol 2013;49(4):243–254. DOI: 10.1016/j.pediatrneurol.2013.08.001.Tuberous.
  23. Toi A, Lister WS, Fong KW. How early are fetal cerebral sulci visible at prenatal ultrasound and what is the normal pattern of early fetal sulcal development? Ultrasound Obstet Gynecol 2004;24(7):706–715. DOI: 10.1002/uog.1802Published online.
  24. Poon LC, Sahota DS, Chaemsaithong P, et al. Transvaginal three-dimensional ultrasound assessment of sylvian fissures at 18–30 weeks’ gestation. Ultrasound Obstet Gynecol 2019;54(2):190–198. DOI: 10.1002/uog.20172.
  25. Pooh RK, Machida M, Nakamura T, et al. Increased sylvian fissure angle as early sonographic sign of malformation of cortical development. Ultrasound Obstet Gynecol 2019;54(2):199–206. DOI: 10.1002/uog.20171.
  26. Dobyns WB. The clinical patterns and molecular genetics of lissencephaly and subcortical band heterotopia. 2010. DOI: 10.1111/j.1528-1167.2009.02433.x.
  27. Di Donato N, Chiari S, Mirzaa GM, et al. Lissencephaly: expanded imaging and clinical classification. Am J Med Genet Part A. 2017(6). DOI: 10.1002/ajmg.a.38245Published online.
  28. Parrini E, Conti V, Dobyns WB, et al. Genetic basis of brain malformations. Mol Syndromol 2016;7(4):220–233. DOI: 10.1159/000448639Published online.
  29. Chen CP, Chang TY, Guo WY, et al. Chromosome 17p13.3 deletion syndrome: ACGH characterization, prenatal findings and diagnosis, and literature review. Gene 2013;532(1):152–159. DOI: 10.1016/j.gene.2013.09.044Published online.
  30. Kato M. Genotype-phenotype correlation in neuronal migration disorders and cortical dysplasias. Front Neurosci 2015;9:181. DOI: 10.3389/fnins.2015.00181Published online.
  31. Alford RE, Bailey AA, Twickler DM. Fetal central nervous system. MRI Fetal Matern Dis Pregnancy 2016. 91–118. DOI: 10.1007/978-3-319-21428-3_6Published online.
  32. Cooper JA. Molecules and mechanisms that regulate multipolar migration in the intermediate zone. Front Cell Neurosci. 2014;8(November):1–11. DOI: 10.3389/fncel.2014.00386.
  33. Hehr U, Uyanik G, Gross C, et al. Novel POMGnT1 mutations define broader phenotypic spectrum of muscle-eye-brain disease. Neurogenetics. 2007;8(4):279–288. DOI: 10.1007/s10048-007-0096-yPublished online.
  34. Vervoort VS, Holden KR, Ukadike KC, et al. POMGnT1 gene alterations in a family with neurological abnormalities. Ann Neurol. 2004;56(1):143–148. DOI: 10.1002/ana.20172Published online.
  35. Biancheri R, Bertini E, Falace A, et al. POMGnT1 mutations in congenital muscular dystrophy. Arch Neurol. 2006;63(10):1491–1495. DOI: 10.1001/archneur.63.10.1491Published online.
  36. Johnson K, Bertoli M, Phillips L, et al. Detection of variants in dystroglycanopathy-associated genes through the application of targeted whole-exome sequencing analysis to a large cohort of patients with unexplained limb-girdle muscle weakness. Skelet Muscle 2018;8(1):1–12. DOI: 10.1186/s13395-018-0170-1.
  37. Aldinger KA, Doherty D. The genetics of cerebellar malformations. Semin Fetal Neonatal Med 2016;21(5):321–332. DOI: 10.1016/j.siny.2016.04.008.
  38. Kousi M, Katsanis N. The genetic basis of hydrocephalus. Annu Rev Neurosci. 2016;39(1):409–435. DOI: 10.1146/annurev-neuro-070815-014023Published online.
  39. Takeda S. Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development. Hum Mol Genet. 2003;12(12):1449–1459. DOI: 10.1093/hmg/ddg153Published online.
  40. Weisstanner C, Kasprian G, Gruber GM, et al. MRI of the fetal brain. Clin Neuroradiol 2015;25(S2):189–196. DOI: 10.1007/s00062-015-0413-z.
  41. Ventruti A, Kazdoba TM, Niu S, et al. Reelin deficiency causes specific defects in the molecular composition of the synapses in the adult brain. Neuroscience 2011;189:32–42. DOI: 10.1016/j.neuroscience.2011.05.050.
  42. Folsom TD, Fatemi SH. The involvement of reelin in neurodevelopmental disorders. Neuropharmacology 2013;68:122 135. DOI: 10.1016/j.neuropharm.2012.08.015Published online.
  43. Van den Veyver IB. Prenatally diagnosed developmental abnormalities of the central nervous system and genetic syndromes: a practical review. Prenat Diagn. 2019;39(9):666–678. DOI: 10.1002/pd.5520.
  44. Ultrasonographic characteristics of cortical sulcus development in the human fetus between 18 and 41 weeks of gestation. Chin Med J (Engl) 2017;130(8):920–928. DOI: 10.4103/0366-6999.204114.
  45. Stutterd CA, Leventer RJ. Polymicrogyria: a common and heterogeneous malformation of cortical development. AJMG 2014;166(2):227–239. DOI: 10.1002/ajmg.c.31399.
  46. Robson SC, Chitty LS, Morris S, et al. Evaluation of array comparative genomic hybridisation in prenatal diagnosis of fetal anomalies: a multicentre cohort study with cost analysis and assessment of patient, health professional and commissioner preferences for array comparative genomic hybridi. Effic Mech Eval. 2017;4(1):1–104. DOI: 10.3310/eme04010.
  47. Leventer RJ, Jansen A, Pilz DT, et al. Clinical and imaging heterogeneity of polymicrogyria: a study of 328 patients. Brain. 2010(Pt 5). DOI: 10.1093/brain/awq078Published online.
  48. Yakovlev PI, Wadsworth. RC. Schizencephalies; a study of the congenital clefts in the cerebral mantle; clefts with hydrocephalus and lips separated. J Neuropathol Exp Neurol. 1946;5(3):169–206. DOI: 10.1097/00005072-194607000-00001.
  49. Barkovich AJ, Kjos BO. Schizencephaly: correlation of clinical findings with MR characteristics. AJNR Am J Neuroradiol. 1992;13(1):85–94.
  50. Bilgüvar K, Öztürk AK, Louvi A, et al. Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature 2010;467(7312):207–210. DOI: 10.1038/nature09327Published online.
  51. Watanabe J, Okamoto K, Ohashi T, et al. Malignant hyperthermia and cerebral venous sinus thrombosis after ventriculoperitoneal shunt in infant with schizencephaly and COL4A1 mutation. World Neurosurg 2019;127:446–450. DOI: 10.1016/j.wneu.2019.04.156Published online LK -
  52. Khalid R, Krishnan P, Blaser S, et al. Fetal vascular origins of schizencephaly. Ann Neurol. 2016. Published online.
  53. Smigiel R, Cabala M, Jakubiak A, et al. Novel COL4A1 mutation in an infant with severe dysmorphic syndrome with schizencephaly, periventricular calcifications, and cataract resembling congenital infection. Birth Defects Res A Clin Mol Teratol 2016;106(4):304–307. DOI: 10.1002/bdra.23488Published online.
  54. Pooh RK. Sonogenetics in fetal neurology. Semin Fetal Neonatal Med 2012;17(6). DOI: 10.1016/j.siny.2012.07.005.
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