Congenital Brain Abnormalities: An Update on Malformations of Cortical Development and Infratentorial Malformations Andrea Poretti, MD 1,2 Eugen Boltshauser, MD 2 Thierry A.G.M. Huisman, MD 1 1 Section of Pediatric Neuroradiology, Division of Pediatric Radiology, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland 2 Division of Pediatric Neurology, University Children’s Hospital, Zurich, Switzerland Semin Neurol 2014;34:239–248. Address for correspondence Andrea Poretti, MD, Section of Pediatric Neuroradiology, Division of Pediatric Radiology, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Charlotte R. Bloomberg Children’s Center, Sheikh Zayed Tower, Room 4174, 1800 Orleans Street, Baltimore, MD 21287-0842 (e-mail: aporett1@jhmi.edu). In the past two decades, significant progress in pre- and postnatal neuroimaging techniques, development of next-gen- eration genetic sequencing, and animal model research has allowed us to advance the correct definition/classification of congenital brain abnormalities and has resulted in a better understanding of their pathogenesis. Classifications of congen- ital brain abnormalities have been proposed based upon neu- roimaging, molecular genetics, and developmental biology. 1–4 Accurate diagnoses of these complex abnormalities are of paramount significance for three primary reasons: (1) to determine inheritance pattern and risk of recurrence, (2) to evaluate for involvement of other systems (e.g., kidneys and liver), and (3) for prognostic implications for the child and family. Neuroimaging plays a key role in the diagnosis of congenital brain abnormalities. Additionally, the neuroimag- ing findings may allow the definition of subphenotypes within a group of congenital brain anomalies and establish correlations between the neuroimaging phenotype and ge- notype (e.g., in lissencephaly). 5 The application of magnetic resonance imaging (MRI) to study congenital brain anomalies includes conventional and advanced techniques. Convention- al MRI sequences allow detailed evaluation of the brain macroanatomy. Advanced MRI sequences provide additional microstructural and functional information that may give insights into pathogenesis. Diffusion tensor imaging (DTI) provides detailed qualitative and quantitative information about microstructure and organization of the white matter tracts. 6 Susceptibility-weighted imaging (SWI) is highly sen- sitive for blood, blood products, and calcifications, and may be helpful in supporting a disruptive pathomechanism. 7 After a short paragraph on the differentiation between a malformation and a disruption, we will discuss the classifica- tion of malformations of cortical development and infraten- torial malformations. Finally, we will discuss in more detail a few selected diseases or groups of diseases: schizencephaly, malformations due to mutations in tubulin genes, and axonal guidance disorders. A detailed discussion of all congenital brain anomalies is beyond the scope of this article. Keywords ► brain ► malformations ► disruptions ► genetics ► neuroimaging ► children Abstract In the past two decades, significant progress in neuroimaging and genetic techniques has allowed for advances in the correct definition/classification of congenital brain abnormalities, which have resulted in a better understanding of their pathogenesis. In addition, new groups of diseases, such as axonal guidance disorders or tubulinopathies, are increasingly reported. Well-defined neuroimaging diagnostic criteria have been suggested for the majority of congenital brain abnormalities. Accurate diagnoses of these complex abnormalities, including distinction between malformations and dis- ruptions, are of paramount significance for management, prognosis, and family counseling. In the next decade, these advances will hopefully be translated into deeper understanding of these disorders and more specific treatments. Issue Theme Neurogenetics; Guest Editor, Ali Fatemi, MD Copyright © 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662. DOI http://dx.doi.org/ 10.1055/s-0034-1386762s. ISSN 0271-8235. 239