Original article Cortical malformations and COL4A1 mutation: Three new cases G. Vitale a , A. Pichiecchio a,b,* , F. Ormitti c , D. Tonduti d , A. Asaro e , L. Farina b , B. Piccolo f , A. Percesepe g , S. Bastianello a,b , S. Orcesi a,h , COL4A1 International Study Group a Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy b Department of Neuroradiology, IRCCS Mondino Foundation, Pavia, Italy c Neuroradiology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy d Child Neurology Unit, V. Buzzi Children's Hospital, Milan, Italy e Genomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, Italy f Child Neuropsychiatry Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy g Medical Genetics, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy h Child and Adolescence Neurology Unit, IRCCS Mondino Foundation, Pavia, Italy article info Article history: Received 25 September 2018 Received in revised form 13 February 2019 Accepted 17 February 2019 abstract Aim: The COL4A1 gene (13q34) encodes the a1 chain of type IV collagen, a crucial compo- nent of the basal membrane. COL4A1 mutations have been identified as a cause of a multisystem disease. Brain MRI in COL4A1-mutated patients typically shows vascular abnormalities and white matter lesions. Cortical malformations (specifically schizencephaly) have also recently been described in these patients, suggesting that these, too, could be part of the phenotypic spectrum of COL4A1 mutations. The aim of our work was to retrospectively evaluate COL4A1-mutated subjects diag- nosed at our centers in order to assess the frequency and define the type of cortical mal- formations encountered in these individuals. Method: We retrospectively reviewed MRI data of 18 carriers of COL4A1 mutations diag- nosed in our centers between 2010 and 2016. Results: We identified polymicrogyria in two patients, and schizencephaly in the mother of a further patient. Interpretation: Our findings confirm that cortical malformations should be considered to fall within the phenotypic spectrum of COL4A1 mutations and show that not only schizence- phaly but also polymicrogyria can also be found in mutated individuals. Although further studies are needed to clarify the underlying pathogenetic mechanism, independently of this, the timing of the brain damage could be the crucial factor determining the type of lesion. © 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. * Corresponding author. Via Mondino 2, 27100, Pavia, Italy. E-mail address: anna.pichiecchio@mondino.it (A. Pichiecchio). Official Journal of the European Paediatric Neurology Society european journal of paediatric neurology xxx (xxxx) xxx https://doi.org/10.1016/j.ejpn.2019.02.006 1090-3798/© 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. Please cite this article as: Vitale G et al., Cortical malformations and COL4A1 mutation: Three new cases, European Journal of Paediatric Neurology, https://doi.org/10.1016/j.ejpn.2019.02.006