Malformations of the Human Cerebral Cortex Patterns and Causes Marie-Claire de Wit de Wit (all).ps Front - 1 T1 - Black CyanMagenta Yellow de Wit_DEF.indd 1 02-08-10 16:31 de Wit (all).ps Back - 1 T1 - Black CyanMagenta Yellow Malformations of the Human Cerebral Cortex Patterns and Causes Aanlegstoornissen van de hersenschors: patronen en oorzaken PROEFSCHRIFT The studies in this thesis were financially supported by The Erasmus MC Revolving Fund ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr. H.G. Schmidt en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op vrijdag 10 september 2010 om 11:30 uur door Marie-Claire Yvette de Wit Financial support for publication: Erasmus University Rotterdam, UCB Pharma B.V., Cyberonics Europe N.V., Sanofi-Aventis Netherlands B.V. geboren te Amsterdam ISBN 978-90-5335-305-9 Cover: neurons in the hippocampal cortex of the brainbow mouse, courtesy of Tamily A. Weissman, Ph.D, Harvard University, USA. Printed by Ridderprint B.V., Ridderkerk. © Marie-Claire de Wit, 2010. No part of this thesis may be reproduced, stored in a retrieval system or transmitted in any form or by any means without permission of the author, or, when appropriate, of the publishers of the publications. de Wit_DEF.indd 2 02-08-10 16:32 de Wit (all).ps Front - 2 T1 - Black CyanMagenta Yellow Malformations of the Human Cerebral Cortex Patterns and Causes Aanlegstoornissen van de hersenschors: patronen en oorzaken PROEFSCHRIFT The studies in this thesis were financially supported by The Erasmus MC Revolving Fund ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr. H.G. Schmidt en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op vrijdag 10 september 2010 om 11:30 uur door Marie-Claire Yvette de Wit Financial support for publication: Erasmus University Rotterdam, UCB Pharma B.V., Cyberonics Europe N.V., Sanofi-Aventis Netherlands B.V. geboren te Amsterdam ISBN 978-90-5335-305-9 Cover: neurons in the hippocampal cortex of the brainbow mouse, courtesy of Tamily A. Weissman, Ph.D, Harvard University, USA. Printed by Ridderprint B.V., Ridderkerk. © Marie-Claire de Wit, 2010. No part of this thesis may be reproduced, stored in a retrieval system or transmitted in any form or by any means without permission of the author, or, when appropriate, of the publishers of the publications. de Wit_DEF.indd 3 02-08-10 16:32 de Wit (all).ps Back - 2 T1 - Black CyanMagenta Yellow PROMOTIECOMMISSIE Promotoren: Prof.dr. W.F.M. Arts Prof.dr. F.G. Grosveld Overige leden: Dr. D.J.J. Halley Malformations of the Human Cerebral Cortex Prof.dr. P.A.E. Sillevis Smitt Prof.dr. D. Lindhout Patterns and Causes Co-promotoren: Dr. I.F.M. de Coo Dr. G.M.S. Mancini de Wit_DEF.indd 4 02-08-10 16:32 de Wit (all).ps Front - 3 T1 - Black CyanMagenta Yellow PROMOTIECOMMISSIE Promotoren: Prof.dr. W.F.M. Arts Prof.dr. F.G. Grosveld Overige leden: Dr. D.J.J. Halley Malformations of the Human Cerebral Cortex Prof.dr. P.A.E. Sillevis Smitt Prof.dr. D. Lindhout Patterns and Causes Co-promotoren: Dr. I.F.M. de Coo Dr. G.M.S. Mancini de Wit_DEF.indd 5 02-08-10 16:32 de Wit (all).ps Back - 3 T1 - Black CyanMagenta Yellow Malformations of the Human Cerebral Cortex: Patterns and Causes Chapter 7 General Discussion 157 TABLE OF CONTENTS Summary 167 Chapter 1 Introduction 9 Samenvatting 171 List of abbreviations 174 Chapter 2 Classification 45 Chapter 2.1 Cortical brain malformations: results of clinical, neuroradiological and 47 Appendix 175 genetic classification. Arch Neurol. 2008 Mar;65(3):358-66. Dankwoord 182 Curriculum vitae 185 Chapter 3 Natural History 65 List of publications 186 Chapter 3.1 Long term follow-up of lissencephaly. 67 [submitted] Portfolio 188 Chapter 3.2 Filamin A mutation, a common cause for periventricular heterotopia, 79 aneurysms and cardiac defects. J Neurol Neurosurg Psychiatry. 2009 Apr;80(4):426-8. Chapter 3.3 Combined cardiological and neurological abnormalities due to filamin A 85 gene mutations. Clin Res Cardiol. 2010, accepted. Chapter 4 New Phenotypes 95 Chapter 4.1 Movement disorder and neuronal migration disorder due to ARFGEF2 97 mutation. Neurogenetics. 2009 Oct;10(4):333-6. Chapter 4.2 Microcephaly with simplified gyral pattern associated with early onset 105 insulin dependent diabetes mellitus. Neurogenetics. 2006 Nov;7(4):259-63. Chapter 5 Metabolic Disorders 115 Chapter 5.1 Brain abnormalities in a case of malonyl-CoA decarboxylase deficiency. 117 Mol Genet Metab. 2006 Feb;87(2):102-6. Chapter 6 Syndromes 129 Chapter 6.1 Periventricular nodular heterotopia and distal limb deficiency: a recurrent 131 association. Am J Med Genet A. 2010 Apr;152A(4):954-9. Chapter 6.2 Unbalanced der(5)t(5;20) translocation associated with megalencephaly, 143 perisylvian polymicrogyria, polydactyly and hydrocephalus . Am J Med Genet A. 2010 Jun;152A(6):1488-97. de Wit_DEF.indd 6 02-08-10 16:32 de Wit (all).ps Front - 4 T1 - Black CyanMagenta Yellow Malformations of the Human Cerebral Cortex: Patterns and Causes Chapter 7 General Discussion 157 TABLE OF CONTENTS Summary 167 Chapter 1 Introduction 9 Samenvatting 171 List of abbreviations 174 Chapter 2 Classification 45 Chapter 2.1 Cortical brain malformations: results of clinical, neuroradiological and 47 Appendix 175 genetic classification. Arch Neurol. 2008 Mar;65(3):358-66. Dankwoord 182 Curriculum vitae 185 Chapter 3 Natural History 65 List of publications 186 Chapter 3.1 Long term follow-up of lissencephaly. 67 [submitted] Portfolio 188 Chapter 3.2 Filamin A mutation, a common cause for periventricular heterotopia, 79 aneurysms and cardiac defects. J Neurol Neurosurg Psychiatry. 2009 Apr;80(4):426-8. Chapter 3.3 Combined cardiological and neurological abnormalities due to filamin A 85 gene mutations. Clin Res Cardiol. 2010, accepted. Chapter 4 New Phenotypes 95 Chapter 4.1 Movement disorder and neuronal migration disorder due to ARFGEF2 97 mutation. Neurogenetics. 2009 Oct;10(4):333-6. Chapter 4.2 Microcephaly with simplified gyral pattern associated with early onset 105 insulin dependent diabetes mellitus. Neurogenetics. 2006 Nov;7(4):259-63. Chapter 5 Metabolic Disorders 115 Chapter 5.1 Brain abnormalities in a case of malonyl-CoA decarboxylase deficiency. 117 Mol Genet Metab. 2006 Feb;87(2):102-6. Chapter 6 Syndromes 129 Chapter 6.1 Periventricular nodular heterotopia and distal limb deficiency: a recurrent 131 association. Am J Med Genet A. 2010 Apr;152A(4):954-9. Chapter 6.2 Unbalanced der(5)t(5;20) translocation associated with megalencephaly, 143 perisylvian polymicrogyria, polydactyly and hydrocephalus . Am J Med Genet A. 2010 Jun;152A(6):1488-97. de Wit_DEF.indd 7 02-08-10 16:32 de Wit (all).ps Back - 4 T1 - Black CyanMagenta Yellow Chapter 1 General Introduction de Wit_DEF.indd 8 02-08-10 16:32 de Wit (all).ps Front - 5 T1 - Black CyanMagenta Yellow Chapter 1 General Introduction de Wit_DEF.indd 9 02-08-10 16:32 de Wit (all).ps Back - 5 T1 - Black CyanMagenta Yellow Chapter 1 General Introduction GENERAL INTRODUCTION 1.2 MCD subtypes Malformations of cortical development can be classified into several subgroups, based on the MRI. The revised Barkovich classification is most widely accepted, and is based on the 1.1 MCD definition and impact 8 proposed underlying mechanisms with a mixture of genetic and imaging criteria. Malformations of cortical development (MCD) are a group of disorders characterized by a Although this classification is not ideal due to these mixed criteria and the fact that not all congenital abnormal structure of the cerebral cortex. In general, malformations are defined patients fit in this model, it is useful to guide the diagnostic process and to group patients as structural abnormalities caused by a disturbance in cell organization or function within with a similar disease. Lissencephaly was the first type of MCD that was recognized as a a tissue type. When a disturbance results in an abnormal structure of the cerebral cortex 9 cause of severe developmental disability over 50 years ago. At the time a definite we call this: malformations of cortical development. MCD are heterogeneous as a group, as diagnosis could only be made by examination of the brain post-mortally. The advent of they include several different structural abnormalities, and they have a diverse array of neuroimaging possibilities, in particular CT scanning in the seventies and MRI scanning in causes, both genetic and environmental. the eighties of the 20th century, enabled physicians to diagnose cortical abnormalities during life. Lissencephaly, being the ‘first MCD’, is also the subtype best described and A patient with a MCD may present to a physician with different neurological symptoms. understood. The brain MRI shows specific features of a thickened cortex with reduced or no These signs and symptoms depend on the regions of the brain that are affected, on the gyration with a predilection for the occipital regions and EEGs show typical high voltage severity of the malformation, and on how much the affected regions still have residual beta activity. Clinically, about all patients have epilepsy and psychomotor delay. The neurological functions or whether normal brain areas can compensate for loss of functions severity correlates with the severity of cortical involvement on MRI [this thesis, chapter (plasticity). As MCD are cortical malformations, functions meant here are the cerebral 3.1]. cortical functions, such as the motor function of the limbs, language development and visual functions. For example, a child may present with a spastic hemiparesis if only one At the same time much progress was made in the possibilities of genetic research.