Introduction: A Practical Guide to Central Nervous System Malformations—From Genetics, to Diagnosis and Treatment

Abstract

Central nervous system (CNS) malformations encompass diverse congenital anomalies impacting brain and spinal cord development, profoundly affecting neurological function. They arise from disruptions in embryonic neural tube formation, neuronal migration, and cortical organization. This abstract provides a comprehensive overview of CNS malformations, covering classification, etiology, clinical manifestations, and diagnostic challenges. CNS malformations fall into distinct groups: neural tube defects (e.g., anencephaly, spina bifida), resulting from incomplete neural tube closure; malformations of cortical development (e.g., lissencephaly, polymicrogyria), featuring irregularities in cortical folding; and anomalies affecting structures like the corpus callosum, cerebellum, and CNS vasculature, alongside conditions such as hydrocephalus and Chiari malformations. Genetic factors, including mutations in LIS1, DCX, and RELN, contribute significantly, while environmental factors like maternal folic acid deficiency also play a role. Some malformations occur in genetic syndromes (e.g., tuberous sclerosis, neurofibromatosis). Clinical presentations vary, with neural tube defects typically presenting severe deficits at birth, while cortical malformations manifest as intellectual disabilities, seizures, and motor deficits. Hydrocephalus elevates intracranial pressure, and Chiari malformations cause headaches and neurological symptoms. Diagnosis necessitates a multidisciplinary approach involving clinical evaluation, neuroimaging, genetic testing, and histopathological analysis. Prenatal diagnosis via ultrasound and magnetic resonance imaging is crucial for planning interventions, while postnatal diagnosis relies on clinical and imaging findings.

Understanding CNS malformations is vital for early detection, intervention, and comprehensive care provision. Advances in genetics and neuroimaging offer hope for improved outcomes and better quality of life for affected individuals.

Keywords

central nervous system malformations - neuronal migration - synapses - environmental factors - classification - epidemiology - genetics - diagnosis - treatment

Publikationsverlauf

Eingereicht: 27. November 2023

Angenommen: 04. April 2024

Artikel online veröffentlicht:
11. Mai 2024

• References

• 1 Pérez-Alfayate R, Grasso G. State of the art and future direction in diagnosis, molecular biology, genetics, and treatment of brain arteriovenous malformations. World Neurosurg 2022; 159: 362-372
• 2 Mirzaa GM, Paciorkowski AR. Introduction: brain malformations. Am J Med Genet C Semin Med Genet 2014; 166C [phone]
• 3 Ganeshan D, Das K. Congenital malformations of the brain. Br J Hosp Med (Lond) 2008; 69 (11) 640-646
• 4 Kim C, Yeom KW, Iv M. Congenital brain malformations in the neonatal and early infancy period. Semin Ultrasound CT MR 2015; 36 (02) 97-119
• 5 Poretti A, Boltshauser E, Huisman TA. Congenital brain abnormalities: an update on malformations of cortical development and infratentorial malformations. Semin Neurol 2014; 34 (03) 239-248
• 6 Severino M, Geraldo AF, Utz N. et al. Definitions and classification of malformations of cortical development: practical guidelines. Brain 2020; 143 (10) 2874-2894
• 7 Barkovich AJ, Guerrini R, Kuzniecky RI, Jackson GD, Dobyns WB. A developmental and genetic classification for malformations of cortical development: update 2012. Brain 2012; 135 (Pt 5): 1348-1369
• 8 Hongo H, Miyawaki S, Teranishi Y. et al. Genetics of brain arteriovenous malformations and cerebral cavernous malformations. J Hum Genet 2023; 68 (03) 157-167
• 9 Maddy K, Chalamgari A, Ariwodo O, Nisseau-Bey Z, Maldonado J, Lucke-Wold B. An updated review on the genetics of arteriovenous malformations. Gene Protein Dis 2023; 2 (02) 312
• 10 Chung C, Yang X, Bae T. et al; Focal Cortical Dysplasia Neurogenetics Consortium, Brain Somatic Mosaicism Network. Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development. Nat Genet 2023; 55 (02) 209-220
• 11 Toulgoat F, Lasjaunias P. Vascular malformations of the brain. Handb Clin Neurol 2013; 112: 1043-1051
• 12 Fletcher JM, Kulesz PA. Brain malformations and spina bifida. Dev Med Child Neurol 2021; 63 (03) 244
• 13 Park KB, Chapman T, Aldinger KA. et al. The spectrum of brain malformations and disruptions in twins. Am J Med Genet A 2021; 185 (09) 2690-2718
• 14 Atamian A, Cordón-Barris L, Quadrato G. Taming human brain organoids one cell at a time. Semin Cell Dev Biol 2021; 111: 23-31
• 15 Zhang DY, Song H, Ming GL. Modeling neurological disorders using brain organoids. Semin Cell Dev Biol 2021; 111: 4-14
• 16 Sarma A, Pruthi S. Congenital brain malformations- update on newer classification and genetic basis. Semin Roentgenol 2023; 58 (01) 6-27
• 17 Chaudhari BP, Ho ML. Congenital brain malformations: an integrated diagnostic approach. Semin Pediatr Neurol 2022; 42: 100973
• 18 Wahl M, Barkovich AJ, Mukherjee P. Diffusion imaging and tractography of congenital brain malformations. Pediatr Radiol 2010; 40 (01) 59-67
• 19 Krishnamurthy R, Wang DJJ, Cervantes B. et al. Recent advances in pediatric brain, spine, and neuromuscular magnetic resonance imaging techniques. Pediatr Neurol 2019; 96: 7-23
• 20 Accogli A, Addour-Boudrahem N, Srour M. Diagnostic approach to cerebellar hypoplasia. Cerebellum 2021; 20 (04) 631-658
• 21 Choi JJ, Setty BN, Lee EY. Brain malformations at all ages: from Aunt Minnie to zebras for general radiologists. Radiol Clin North Am 2020; 58 (03) 463-474
• 22 Pavone P, Praticò AD, Rizzo R. et al. A clinical review on megalencephaly: a large brain as a possible sign of cerebral impairment. Medicine (Baltimore) 2017; 96 (26) e6814
• 23 Praticò AD, Polizzi A, Salafia R. et al. Megalencephaly capillary malformation syndrome. J Pediatr Neurol 2018; 16: 328-337
• 24 Praticò AD, Falsaperla R, Comella M, Belfiore G, Polizzi A, Ruggieri M. Case report: a gain-of-function of hamartin may lead to a distinct “inverse TSC1-hamartin” phenotype characterized by reduced cell growth. Front Pediatr 2023; 11: 1101026
• 25 Bulakbasi N, Cancuri O, Kocaoğlu M. The middle interhemispheric variant of holoprosencephaly: magnetic resonance and diffusion tensor imaging findings. Br J Radiol 2016; 89 (1063) 20160115