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      Moebius Syndrome: An Updated Review of Literature

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          Abstract

          Moebius Syndrome, is a rare, non-progressive congenital neuropathological syndrome characterized primarily by the underdevelopment of the facial (CN VII) and abducens nerve (CN VI). Other features of Moebius Syndrome include facial nerve paresis, ophthalmoplegias, orthodontic deficiencies (including crowded dentition, swollen and hyperplastic gingiva, dental calculus, etc.), musculoskeletal abnormalities, and impaired mental function. Due to the rarity of the disorder, very few case studies have been reported in the literature. This article summarizes the significant features of the disease according to commonalities in reported cases, along with several newly recognized features cited in recent literature. We have explored the different diagnostic criteria and the newly recognized imaging modalities that may be used. Understandably, the condition detrimentally affects a patient’s quality of life; thus, treatment measures have also been outlined. This study aims to provide updated literature on Moebius Syndrome MBS and improve understanding of the condition.

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          Most cited references99

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          Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance.

          We report that eight heterozygous missense mutations in TUBB3, encoding the neuron-specific beta-tubulin isotype III, result in a spectrum of human nervous system disorders that we now call the TUBB3 syndromes. Each mutation causes the ocular motility disorder CFEOM3, whereas some also result in intellectual and behavioral impairments, facial paralysis, and/or later-onset axonal sensorimotor polyneuropathy. Neuroimaging reveals a spectrum of abnormalities including hypoplasia of oculomotor nerves and dysgenesis of the corpus callosum, anterior commissure, and corticospinal tracts. A knock-in disease mouse model reveals axon guidance defects without evidence of cortical cell migration abnormalities. We show that the disease-associated mutations can impair tubulin heterodimer formation in vitro, although folded mutant heterodimers can still polymerize into microtubules. Modeling each mutation in yeast tubulin demonstrates that all alter dynamic instability whereas a subset disrupts the interaction of microtubules with kinesin motors. These findings demonstrate that normal TUBB3 is required for axon guidance and maintenance in mammals.
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            Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome.

            CHARGE syndrome [coloboma of the eye, heart defects, atresia of the choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities (including deafness)] is a genetic disorder characterized by a specific and a recognizable pattern of anomalies. De novo mutations in the gene encoding chromodomain helicase DNA binding protein 7 (CHD7) are the major cause of CHARGE syndrome. Here, we review the clinical features of 379 CHARGE patients who tested positive or negative for mutations in CHD7. We found that CHARGE individuals with CHD7 mutations more commonly have ocular colobomas, temporal bone anomalies (semicircular canal hypoplasia/dysplasia), and facial nerve paralysis compared with mutation negative individuals. We also highlight recent genetic and genomic studies that have provided functional insights into CHD7 and the pathogenesis of CHARGE syndrome. (c) 2010 Wiley-Liss, Inc.
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              Stac3 is a component of the excitation-contraction coupling machinery and mutated in Native American myopathy

              Excitation-contraction coupling, the process that regulates contractions by skeletal muscles, transduces changes in membrane voltage by activating release of Ca2+ from internal stores to initiate muscle contraction. Defects in EC coupling are associated with muscle diseases. Here we identify Stac3 as a novel component of the EC coupling machinery. Using a zebrafish genetic screen, we generate a locomotor mutation that is mapped to stac3. We provide electrophysiological, Ca2+ imaging, immunocytochemical and biochemical evidence that Stac3 participates in excitation-contraction coupling in muscles. Furthermore, we reveal that a mutation in human STAC3 as the genetic basis of the debilitating Native American myopathy (NAM). Analysis of NAM stac3 in zebrafish shows that the NAM mutation decreases excitation-contraction coupling. These findings enhance our understanding of both excitation-contraction coupling and the pathology of myopathies.
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                Author and article information

                Journal
                Child Neurol Open
                Child Neurol Open
                CNO
                spcno
                Child Neurology Open
                SAGE Publications (Sage CA: Los Angeles, CA )
                2329-048X
                18 October 2023
                Jan-Dec 2023
                : 10
                : 2329048X231205405
                Affiliations
                [1 ]Department of Internal Medicine, Ringgold 37093, universityZiauddin Medical University; , Karachi, Pakistan
                [2 ]Department of Internal Medicine, Dow Medical College, Ringgold 66818, universityDow University of Health Sciences; , Karachi, Pakistan
                Author notes
                [*]Sajjad Ali, Department of Internal Medicine, Ziauddin Medical University, 4/B, Saharah-e-Ghalib, Block 6, Clifton, Karachi – 75600Sindh, Pakistan. Email: sajjad110@ 123456live.com
                Author information
                https://orcid.org/0000-0002-8024-5942
                Article
                10.1177_2329048X231205405
                10.1177/2329048X231205405
                10588417
                37868706
                316e2137-cb41-44a0-8af9-ed856b3849ce
                © The Author(s) 2023

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 29 May 2023
                : 21 August 2023
                : 8 September 2023
                Categories
                Topical Review Article
                Custom metadata
                ts19
                January-December 2023

                moebius syndrome,poland syndrome,facial nerve paralysis,abducens nerve paralysis

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