Case Report Holoprosencephaly with cerebellar vermis hypoplasia in 13q deletion syndrome: Critical region for cerebellar dysgenesis within 13q32.2q34 Masakazu Mimaki a,⇑ , Takashi Shiihara b , Mio Watanabe b , Kyoko Hirakata c , Satoru Sakazume d , Akio Ishiguro a , Keiko Shimojima e , Toshiyuki Yamamoto e , Akira Oka a , Masashi Mizuguchi a,f a Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Japan b Department of Neurology, Gunma Children’s Medical Center, Japan c Department of Ophthalmology, Gunma Children’s Medical Center, Japan d Clinical Genetics Center, Dokkyo Medical University Koshigaya Hospital, Japan e Tokyo Women’s Medical University Institute for Integrated Medical Sciences, Japan f Developmental Medical Sciences, Graduate School of Medicine, The University of Tokyo, Japan Received 8 July 2014; received in revised form 4 October 2014; accepted 16 October 2014 Abstract We describe two unrelated patients with terminal deletions in the long arm of chromosome 13 showing brain malformation con- sisting of holoprosencephaly and cerebellar vermis hypoplasia. Array comparative genomic hybridization analysis revealed a pure terminal deletion of 13q31.3q34 in one patient and a mosaic ring chromosome with 13q32.2q34 deletion in the other. Mutations in ZIC2, located within region 13q32, cause holoprosencephaly, whereas the 13q32.2q32.3 region is associated with cerebellar vermis hypoplasia (Dandy–Walker syndrome). The rare concurrence of these major brain malformations in our patients provides further evidence that 13q32.2q32.3 deletion, harboring ZIC2 and ZIC5, leads to cerebellar dysgenesis. Ó 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. Keywords: Chromosome 13; Distal 13q deletion; Cerebellar vermis hypoplasia 1. Introduction Variable central nervous system (CNS) anomalies such as holoprosencephaly (HPE), agenesis of the corpus callosum, neural tube defects (NTDs), and Dandy–Walker malformation (DWM) have been reported in the 13q deletion syndrome [1–6]. However, the concurrent occurrence of HPE and DWM, which is characterized by cerebellar vermis hypoplasia or apla- sia, is rare [3]. Here we present the clinical features and molecular cytogenetic characterizations of two patients with 13q deletion including the 13q32.2q34 region. Both patients exhibited multiple anomalies, including HPE and cerebellar vermis hypoplasia. http://dx.doi.org/10.1016/j.braindev.2014.10.009 0387-7604/Ó 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. ⇑ Corresponding author at: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Tel.: +81 3 5800 8659; fax: +81 3 3816 4108. E-mail address: mimaki-tky@umin.ac.jp (M. Mimaki). www.elsevier.com/locate/braindev Brain & Development xxx (2014) xxx–xxx Please cite this article in press as: Mimaki M et al. Holoprosencephaly with cerebellar vermis hypoplasia in 13q deletion syndrome: Critical region for cerebellar dysgenesis within 13q32.2q34. Brain Dev (2014), http://dx.doi.org/10.1016/j.braindev.2014.10.009