Iran J Pediatr. 2021 August; 31(4):e111431. Published online 2021 August 30. doi: 10.5812/ijp.111431. Case Report Frameshift Mutation in Polar Rich Domain (PRD) of PQBP1 Gene Associated with Asymmetric Cerebellar Hemispheres: A Case Report of Renpenning Syndrome Dejan Aleksic 1, * , Milan Borkovic 2 , Jelena Krivacic 3 , Igor Petrusic 4 and Vedrana Milic Rasic 5 1 Department of Neurology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia 2 Clinic for Neurology and Psychiatry for Children and Youth, Belgrade, Serbia 3 Institute for Psychophysiological Disorders and Speech Pathology "Prof. Dr Cvetko Brajovic", Belgrade, Serbia 4 Laboratory for Advanced Analysis of Neuroimages, Faculty of Physical Chemistry, University of Belgrade, Belgrade, Serbia 5 Clinic for Neurology and Psychiatry for Children and Youth, School of Medicine, University of Belgrade, Belgrade, Serbia * Corresponding author: Department of Neurology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia. Email: drdeal1987@gmail.com Received 2020 November 21; Revised 2021 June 18; Accepted 2021 July 27. Abstract Introduction: In 1962, Renpenning et al. published an article with 20 male patients from three generations with mental retar- dation. Scientists suggested that the syndrome with mutation mapped to the locus Xp11.2-p11.4 should be called Renpenning syn- drome. The deletion/duplication of an AG dinucleotide on proximal Xp in the polyglutamine tract-binding protein 1 (PQBP1) gene causing frameshift in the fourth coding exon was identified as the most frequent mutation in this syndrome. Renpenning syndrome with asymmetric cerebellar hemispheres has not been reported previously. Case Presentation: In this case report, we presented an 11-year-old male with mild developmental delay and mild intellectual dis- ability, microcephaly, dysmorphic face, short stature, and seizures. The following morphological abnormalities were detected: a wide nasal bridge, midfacial hypoplasia, short philtrum, low-set ears, low hanging columella, high palate, and narrow face. Neuro- logical examination showed upper and lower extremities hypotonia with joint hypermobility. The patient had his first seizure at the age of seven, and he experienced a total of 10 seizures by the age 11. A systolic murmur of intensity 2/6 was present, and echocardiog- raphy showed chordae tendineae abnormalities in the left ventricle. Brain magnetic resonance imaging (MRI) showed asymmetric cerebellar hemispheres (mild right cerebellar hemisphere hypoplasia). A frameshift mutation in the polar reach domain (PRD) of the PQBP1 gene (c.459-462 delAGAG) was detected by exome sequencing. Conclusions: We showed the first case of genetically confirmed Renpenning syndrome in Serbia. Our patient had classical clinical manifestations for Renpenning syndrome as a consequence of frameshift mutation in the PRD of the PQBP1 gene. To the best of our knowledge, according to the literature, this is the first patient with Renpenning syndrome with asymmetric cerebellar hemispheres (mild right cerebellar hemisphere hypoplasia). Keywords: PQBP1 Gene, Polar Rich Domain, Cerebellar Hypoplasia, Renpenning Syndrome, Seizures 1. Introduction Renpenning et al. (1) published an article in 1962 with 20 male patients from three generations with mental re- tardation (MR), which were associated with microcephaly, prominent ears, cataracts, congenital ocular coloboma, and seizures. Turner et al. (2), from a group of 148 males with intellectual disability (ID), analyzed 17 who were con- sidered to have that same syndrome because of the same pattern of inheritance. Scientists mapped the locus to Xp11.2-p11.4 and suggested that the syndrome with this mu- tation should be called Renpenning syndrome (3). In five of 29 families with X-linked mental retardation (XLMR), the deletion/duplication of an AG dinucleotide on proximal Xp in the polyglutamine tract-binding protein 1 (PQBP1) gene was identified, causing frameshift in the fourth cod- ing exon (4). Stevenson et al. (5) identified a 4-bp deletion in exon 4 of the PQBP1 gene denoted by the mutation as 459-462delAGAG. It was then proposed that all mutations in the PQBP1 gene whose clinical manifestations over time received different names in the literature were unified un- der the same name: Renpenning syndrome (5). Also, this mutation in the PQBP1 gene (the fourth coding exon) has Copyright © 2021, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.