Brain Malformations

Renske Oegema is an internationally recognized expert regarding congenital brain malformations. Her focus is on malformations of the brain cortex, a.k.a. malformations of cortical development (MCD), for example heterotopia, polymicrogyria and lissencephaly.

To accelerate research collaborations, and to share and disseminate knowledge she co-founded and was co-leader of the European network for brain malformations Neuro-MIG (2016-2021). https://www.neuro-mig.org/

Selected publications:

Renske Oegema, Tahsin Stefan Barakat, Martina Wilke, Katrien Stouffs, Dina Amron, Eleanora Aronica, Nadia Bahi-Buisson, Valerio Conti, Andrew E. Fry, Tobias Geis, David Gomez Andres, Elena Parrini, Edith Said, Dorriete Soler, Luis M. Valor Maha Zaki, Ghayda Mirzaa, William B Dobyns, Renzo Guerrini, Daniela Pilz, Ute Hehr, Richard J. Leventer, Anna Jansen, Grazia M.S. Mancini, Nataliya Di Donato. Malformations of cortical development, international consensus recommendations on diagnostic workup. Nature Reviews Neurology 2020 Nov;16(11):618-635.

Vriend I, Oegema R. Genetic causes underlying grey matter heterotopia. Eur J Paediatr Neurol. 2021 Nov;35:82-92. doi: 10.1016/j.ejpn.2021.09.015.

Renske Oegema, A. James Barkovich, Grazia M. S. Mancini, Renzo Guerrini, and William B. Dobyns. Subcortical heterotopic gray matter brain malformations: classification study of 107 individuals. Neurology. 2019 Oct 1;93(14):e1360-e1373. [IF 8.055]

KDM2B

The group has, through international collaboration, delineated a novel neurodevelopmental syndrome cause by mutations in the KDM2B gene (Van Jaarsveld et al, submitted). KDM2B is an epigenetic regulator and we have established an distinct KDM2B episignature, in collaboration with Marielle Alders (Amsterdam UMC) and Bekim Sadikovic (London, Canada). We aim to expand the patient cohort to study the clinical features associated with this syndrome. In parallel we are developing an in vitro neuronal cell model to study the effect of KDM2B mutations. For more information, please contact us at [email protected].

In the future, we aim to expand our study to our epigenetic disorders affecting neurodevelopment.

Selected publications

Levy MA, McConkey H, Kerkhof J, Barat-Houari M, Bargiacchi S, Biamino E, Bralo MP, Cappuccio G, Ciolfi A, Clarke A, DuPont BR, Elting MW, Faivre L, Fee T, Fletcher RS, Cherik F, Foroutan A, Friez MJ, Gervasini C, Haghshenas S, Hilton BA, Jenkins Z, Kaur S, Lewis S, Louie RJ, Maitz S, Milani D, Morgan AT, Oegema R, Østergaard E, Pallares NR, Piccione M, Pizzi S, Plomp AS, Poulton C, Reilly J, Relator R, Rius R, Robertson S, Rooney K, Rousseau J, Santen GWE, Santos-Simarro F, Schijns J, Squeo GM, St John M, Thauvin-Robinet C, Traficante G, van der Sluijs PJ, Vergano SA, Vos N, Walden KK, Azmanov D, Balci T, Banka S, Gecz J, Henneman P, Lee JA, Mannens MMAM, Roscioli T, Siu V, Amor DJ, Baynam G, Bend EG, Boycott K, Brunetti-Pierri N, Campeau PM, Christodoulou J, Dyment D, Esber N, Fahrner JA, Fleming MD, Genevieve D, Kerrnohan KD, McNeill A, Menke LA, Merla G, Prontera P, Rockman-Greenberg C, Schwartz C, Skinner SA, Stevenson RE, Vitobello A, Tartaglia M, Alders M, Tedder ML, Sadikovic B. Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders. HGG Adv. 2021 Dec 3;3(1):100075. doi: 10.1016/j.xhgg.2021.100075.  PMID: 35047860

Levy MA, Beck DB, Metcalfe K, Douzgou S, Sithambaram S, Cottrell T, Ansar M, Kerkhof J, Mignot C, Nougues MC, Keren B, Moore HW, Oegema R, Giltay JC, Simon M, van Jaarsveld RH, Bos J, van Haelst M, Motazacker MM, Boon EMJ, Santen GWE, Ruivenkamp CAL, Alders M, Luperchio TR, Boukas L, Ramsey K, Narayanan V, Schaefer GB, Bonasio R, Doheny KF, Stevenson RE, Banka S, Sadikovic B, Fahrner JA. Deficiency of TET3 leads to a genome-wide DNA hypermethylation episignature in human whole blood. NPJ Genom Med. 2021 Nov 8;6(1):92. doi: 10.1038/s41525-021-00256-y. PMID: 34750377

Van Jaarsveld et al. Delineation of a KDM2B-related neurodevelopmental disorder and its associated DNA methylation signature, Genetics in Medicine 2023. 

I work as a Clinical Geneticist and Assistant Professor in the UMC Utrecht. I engage daily with patients afflicted by neurodevelopmental disorders (NDDs) such as autism and epilepsy. In 2018 I took a leading role in setting up the multidisciplinary clinic for developmental disorders in the UMC Utrecht Wilhelmina Children’s Hospital, providing early diagnostics and support for children with developmental delay. Witnessing their long diagnostic odyssey and lack of effective treatments strongly fuels my dedication to enhance our understanding of these disorders. I effectively combine my clinical and research skills by leading a translational research group. My research  is centered around four objectives:

-       Discovering novel disease genes and variants implicated in NDDs

-       Establishing and analyzing patient cohorts of rare/ newly discovered NDDs

-       Developing functional assays/ biomarkers to assess rare genomic variants

-       Unravelling underlying disease mechanisms using in vitro cellular models

I integrated my PhD on Malformations of Cortical Development (MCD) with my clinical training in the Department of Clinical Genetics at the Erasmus MC, Rotterdam (2011-2016). During this trajectory my primary focus was on neurogenetics and gene discovery, for which I obtained comprehensive training in syndrome delineation, brain imaging and genotype-phenotype analysis. Concurrently, I obtained laboratory skills, including culturing cell lines, immunofluorescence, and the analysis of exome and genome sequencing and genome-wide expression data.

Recently, I have delineated a novel NDD, the KDM2B-associated syndrome. My group is currently investigating the molecular mechanisms of the KDM2B syndrome and its effect in neuronal differentiation. We employ in vitro neuronal cell models, utilizing induced pluripotent stem cells technologies to differentiate patients’ cells into neuronal cell lines.

To accelerate research collaborations, and to share and disseminate knowledge I acted a co-founder and co-leader of the European network for brain malformations Neuro-MIG (2016-2021). I regularly perform peer reviews and I have contributed to patient information on the websites of the Dutch Epilepsy foundation (EpilepsieNL) and Brain Foundation (Hersenstichting).