Clinical Neurology and Neuroscience 2022; 6(1): 1-5 http://www.sciencepublishinggroup.com/j/cnn doi: 10.11648/j.cnn.20220601.11 ISSN: 2578-8922 (Print); ISSN: 2578-8930 (Online) Extrapyramidal Involvement as a Manifestation of ROBO3 Mutation in HGPPS: A Case Report and Review of Literatures Matineh Heidari 1 , Tara Khoeini 1 , Mostafa Almasi Dooghaee 1 , Omid Aryani 2 , Zahra Mirzaasgari 1, * 1 Neurology Department of Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran 2 Department of Neuroscience, Iran University of Medical Science, Tehran, Iran Email address: * Corresponding author To cite this article: Matineh Heidari, Tara Khoeini, Mostafa Almasi Dooghaee, Omid Aryani, Zahra Mirzaasgari. Extrapyramidal Involvement as a Manifestation of ROBO3 Mutation in HGPPS: A Case Report and Review of Literatures. Clinical Neurology and Neuroscience. Vol. 6, No. 1, 2022, pp. 1-5. doi: 10.11648/j.cnn.20220601.11 Received: October 1, 2021; Accepted: October 28, 2021; Published: January 12, 2022 Abstract: HGPPS (horizontal gaze palsy with progressive scoliosis) presents in early childhood ages and one of the cardinal manifestations of the syndrome, progressive scoliosis, is the main disabling feature which usually seeks for orthopedic correction surgeries in early years. Nevertheless, the presence of scoliosis has not been explained yet by the pathogenesis of the disease, the ROBO3 mutation, which is a well-known pathology for gaze palsy by failure of axonal decussation toward the pontomedullary junction. This article highlights a novel case of HGPPS with prominent extrapyramidal findings including torticollis, cervical dystonia and facial spasm along with classic clinical, imaging and genetic correlation. Aiming to investigate the prevalence of extrapyramidal signs in this syndrome, the published cases of HGPPS in the literature have been reviewed in this study. 32% of all HGPPS cases between years of 1975 to 2020 founded to have one or more extrapyramidal features and the dystonia was the most reported sign which even proceed to the presence of scoliosis. Regarding to the fact that the scoliosis could be as a consequence of axial dystonia, its relationship to ROBO3 mutation can be explained by structural and functional changes toward the brainstem and cerebellum, which are involved in this syndrome and known to contribute with the extrapyramidal system. Knowing this possibility, not only could solve the 35-year mystery of scoliosis in the syndrome, but also would be considered as a target of treatment to prevent scoliosis in the future. Keywords: Horizontal Gaze Palsy with Progressive Scoliosis, Extrapyramidal, Dystonia, Movement Disorder, Neurogenetic 1. Introduction Horizontal gaze palsy with progressive scoliosis (HGPPS), is an autosomal recessive disease due to ROBO3 mutation, which results in dysregulation of axonal midline decussation process of motor and sensory pathways during the development of the central nervous system [1]. Uncrossed corticospinal, dorsal column and medial lemniscus pathways leads to malformation and malfunction of the inferior pons and medulla which is visualized with a specific imaging appearance [2] There are many case reports since 1975 to the recent, focusing on the clinical features, structural and functional MRI correlations and detailed genetic mapping of the disease [3, 4], Nevertheless, some ambiguities about the pathophysiology of the syndrome still exist. The scoliosis, one of the cardinal manifestations of the syndrome is not fully understood yet by the ROBO3 malfunction. Furthermore, persistence of some unusual clinical findings reported in various published cases such as torticollis, facial spasm and cervical dystonia, have not been favorably explained or linked to the disease. Recently it has been addressed that torticollis which has been reported in several studies, can be a reason for discovery [5]. In this article, following the presentation of a confirmed case of HGPPS with remarkable extrapyramidal signs along with classical manifestations of the syndrome, the previous published cases of HGPPS are evaluated with respect to extrapyramidal involvement, in order to estimate the