Keywords Cerebellar ataxia, neuropathy,...

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome
Richard D Turner, Barnaby Hirons, Andrea Cortese, Surinder S Birring
Chronic cough is common, and in many cases unexplained or refractory to otherwise effective treatment of associated medical conditions. Cough hypersensitivity has developed as a paradigm that helps to explain clinical and research observations that frequently point towards chronic cough as a neuropathic disorder. Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recently described neurological condition whose clinical features include gait ataxia, unsteadiness, peripheral neuropathy, and autonomic dysfunction...
November 18, 2023: Lung
Nishu Tyagi, Bharathram Uppili, Pooja Sharma, Shaista Parveen, Sheeba Saifi, Abhinav Jain, Akhilesh Sonakar, Istaq Ahmed, Shweta Sahni, Uzma Shamim, Avni Anand, Varun Suroliya, Vivekanand Asokachandran, Achal Srivastava, Sridhar Sivasubbu, Vinod Scaria, Mohammed Faruq
An intronic bi-allelic pentanucleotide repeat expansion mutation, (AAGGG)400-2000 , at AAAAG repeat locus in RFC1 gene, is known as underlying genetic cause in cases with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) and late-onset sporadic ataxia. Biallelic positive cases carry a common recessive risk haplotype, "AAGA," spanning RFC1 gene. In this study, our aim is to find prevalence of bi-allelic (AAGGG)exp in Indian ataxia and other neurological disorders and investigate the complexity of RFC1 repeat locus and its potential association with neurodegenerative diseases in Indian population-based cohorts...
November 2, 2023: Neurogenetics
Esther Palones, Elena Curto, Vicente Plaza, Lidia Gonzalez-Quereda, Alba Segarra-Casas, Luis Querol, Federico Bertoletti, María José Rodriguez, Pía Gallano, Astrid Crespo-Lessmann
Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is an hereditary autosomal recessive disease. Recent studies propose including chronic cough (CC) as a symptom of CANVAS. For 10 patients with CANVAS as genetically confirmed by biallelic expansion of the AAGG repeat motif (AAGGGexp) in intron 2 of replication factor C subunit 1 (RFC1), our aim was, as a multidisciplinary team, to describe clinical and functional characteristics and possible causes of CC following European Respiratory Society (ERS) recommendations, and to evaluate CC impact on quality of life (QoL) using self-administered questionnaires (Cough Severity Diary, Leicester Cough Questionnaire, Discrete Emotions Questionnaire, and EQ-5D-5L)...
November 2, 2023: Journal of Neurology
Stefano Facchini, Natalia Dominik, Arianna Manini, Stephanie Efthymiou, Riccardo Currò, Bianca Rugginini, Elisa Vegezzi, Ilaria Quartesan, Benedetta Perrone, Shahedah Koya Kutty, Valentina Galassi Deforie, Ricardo P Schnekenberg, Elena Abati, Anna Pichiecchio, Enza Maria Valente, Cristina Tassorelli, Mary M Reilly, Henry Houlden, Enrico Bugiardini, Andrea Cortese
A recessive Short Tandem Repeat expansion in RFC1 has been found to be associated with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), and to be a frequent cause of late onset ataxia and sensory neuropathy. The usual procedure for sizing these expansions is based on Southern Blotting (SB), a time-consuming and a relatively imprecise technique. In this paper, we compare SB with Optical Genome Mapping (OGM), a method for detecting Structural Variants (SVs) based on the measurement of distances between fluorescently labelled probes, for the diagnosis of RFC1 CANVAS and disease spectrum...
October 19, 2023: Biomolecules
Giulia Di Rauso, Andrea Castellucci, Francesco Cavallieri, Andrea Tozzi, Valentina Fioravanti, Edoardo Monfrini, Annalisa Gessani, Jessica Rossi, Isabella Campanini, Andrea Merlo, Dario Ronchi, Manuela Napoli, Rosario Pascarella, Sara Grisanti, Giuseppe Ferrulli, Rossella Sabadini, Alessio Di Fonzo, Angelo Ghidini, Franco Valzania
(1) Background: Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is characterized by late-onset cerebellar ataxia, bilateral vestibulopathy, and sensory neuronopathy mostly due to biallelic RFC1 expansion. (2) Objectives: The aim of this case series is to describe vestibular, gait, and speech alterations in CANVAS via a systematic approach. (3) Methods: All patients (n = 5) underwent a standardized clinical-instrumental examination, including the perceptual and acoustic analysis of speech, instrumental gait, and balance analysis (posturographic data were acquired using a force plate [Kistler, Winterthur, Switzerland] while 3D gait analysis, inclusive of surface electromyography, was acquired using a motion capture system [SMART DX, BTS Bioengineering, Milan, Italy], a wireless electromyograph [FreeEMG, BTS Bioengineering, Milan, Italy]), and vestibular assessment with video-oculography...
October 17, 2023: Brain Sciences
R G Harrell, A R Cassidy, B N Klatt, P Hovareshti, S L Whitney
BACKGROUND AND PURPOSE: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a neurodegenerative disease of the cerebellum. The disease progression is slow, with up to 25% of people diagnosed needing to use a wheelchair after 15 years from diagnosis. Vestibular symptoms arise from centrally-mediated ocular movement degradation and the reduced vestibular-ocular reflex functioning bilaterally. To date, no report has shown an improvement in VOR gain or gait outcome measures in someone with CANVAS after a course of vestibular physical therapy...
October 2023: Journal of Otology
Makito Hirano, Motoi Kuwahara, Yuko Yamagishi, Makoto Samukawa, Kanako Fujii, Shoko Yamashita, Masahiro Ando, Nobuyuki Oka, Mamoru Nagano, Taro Matsui, Toshihide Takeuchi, Kazumasa Saigoh, Susumu Kusunoki, Hiroshi Takashima, Yoshitaka Nagai
Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) has recently been attributed to biallelic repeat expansions in RFC1. More recently, the disease entity has expanded to atypical phenotypes, including chronic neuropathy without cerebellar ataxia or vestibular areflexia. Very recently, RFC1 expansions were found in patients with Sjögren syndrome who had neuropathy that did not respond to immunotherapy. In this study RFC1 was examined in 240 patients with acute or chronic neuropathies, including 105 with Guillain-Barré syndrome or Miller Fisher syndrome, 76 with chronic inflammatory demyelinating polyneuropathy, and 59 with other types of chronic neuropathy...
October 18, 2023: Scientific Reports
Leslie H Hayes, Reza Sadjadi
OBJECTIVE: This article provides an overview of hereditary neuropathies, describes the different hereditary neuropathy subtypes and the clinical approach to differentiating between them, and summarizes their clinical management. LATEST DEVELOPMENTS: Increasingly available clinical genetic testing has broadened the clinical spectrum of hereditary neuropathy subtypes and demonstrated a significant overlap of phenotypes associated with a single gene. New subtypes such as SORD -related neuropathy and CANVAS (cerebellar ataxia, neuropathy, vestibular areflexia syndrome) have emerged...
October 1, 2023: Continuum: Lifelong Learning in Neurology
María Fernandez-Rueda, Alfredo García-Fernández, Joaquín Jesús De Vergas-Gutiérrez
BACKGROUND: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) presents an unpredictable and uneven clinical development of cerebellar ataxia, neuropathy, and vestibular areflexia. The aim of this study is to report the variability of vestibular test results in genetically confirmed patients with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome. METHODS: Caloric testing, video head impulse test (vHIT), and rotatory chair testing were performed in 7 patients who presented pathogenic repeat expansions in the replication factor complex unit 1 gene related to cerebellar ataxia, neuropathy, and vestibular areflexia syndrome...
October 2023: Journal of International Advanced Otology
Vasco Sousa Abreu, José Sá Silva, Liliana Igreja, Maria João Malaquias, Catarina Mendes Pinto
The well-known eye-of-the-tiger sign features bilateral and symmetrical changes in the globus pallidus, with a central area of high signal and peripheral low signal on T2-weighted MRI. Although formally considered pathognomonic of pantothenate kinase-associated neurodegeneration (PKAN), there are other neurodegenerative or genetic diseases showing similar findings. Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a late-onset ataxia, that was recently associated with biallelic AAGGG repeat expansion in the RFC1 gene...
September 25, 2023: American Journal of Medical Genetics. Part A
Maria João Malaquias, Luis Braz, Cláudia Santos Silva, Joana Damásio, André Jorge, João M Lemos, Catarina F Campos, Daniela Garcez, Miguel Oliveira Santos, Ana G Velon, André Caetano, Margarida Calejo, Preza Fernandes, Ângela Rego, Sandra Castro, Ana P Sousa, Marcio Neves Cardoso, Marco Fernandes, Miguel M Pinto, Ricardo Taipa, Ana M Lopes, Jorge Oliveira, Marina Magalhães
BACKGROUND AND OBJECTIVES: The RFC1 spectrum has become considerably expanded as multisystemic features beyond the triad of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) have started to be unveiled, although many still require clinical replication. Here, we aimed to clinically characterize a cohort of RFC1 -positive patients by addressing both classic and multisystemic features. In a second part of this study, we prospectively assessed small nerve fibers (SNF) and autonomic function in a subset of these RFC1 -related patients...
October 2023: Neurology. Clinical Practice
Mohammad Hossein Abdi, Bita Zamiri, Gholamreza Pazuki, Soroush Sardari, Christopher E Pearson
Biallelic expansions of various tandem repeat sequence motifs are possible in RFC1, encoding the DNA replication/repair protein RFC1, yet only certain repeat motifs cause cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). CANVAS presents enigmatic puzzles: The pathogenic path for CANVAS is unknown, nor is it understood why some, but not all expanded motifs are pathogenic. The most common pathogenic repeat is (AAGGG)n•(CCCTT)n, while (AAAAG)n•(CTTTT)n is the most common non-pathogenic motif...
September 1, 2023: Journal of Biological Chemistry
Carolin K Scriba, Igor Stevanovski, Sanjog R Chintalaphani, Hasindu Gamaarachchi, Roula Ghaoui, Darshan Ghia, Robert D Henderson, Nerissa Jordan, Antony Winkel, Phillipa J Lamont, Miriam J Rodrigues, Richard H Roxburgh, Ben Weisburd, Nigel G Laing, Ira W Deveson, Mark R Davis, Gianina Ravenscroft
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome is a progressive, generally late-onset, neurological disorder associated with biallelic pentanucleotide expansions in Intron 2 of the RFC1 gene. The locus exhibits substantial genetic variability, with multiple pathogenic and benign pentanucleotide repeat alleles previously identified. To determine the contribution of pathogenic RFC1 expansions to neurological disease within an Australasian cohort and further investigate the heterogeneity exhibited at the locus, a combination of flanking and repeat-primed PCR was used to screen a cohort of 242 Australasian patients with neurological disease...
2023: Brain communications
Matteo Tagliapietra, Alex Incensi, Moreno Ferrarini, Nazarena Mesiano, Alessandro Furia, Giovanni Rizzo, Rocco Liguori, Tiziana Cavallaro, Salvatore Monaco, Gian Maria Fabrizi, Vincenzo Donadio
BACKGROUND: biallelic mutation/expansion of the gene RFC1 has been described in association with a spectrum of manifestation ranging from isolate sensory neuro(no)pathy to a complex presentation as Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS). Our aim was to define the frequency and characteristics of small fiber neuropathy (SFN) in RFC1-disease at different stages. METHODS: RFC1-cases were screened for SFN using the Neuropathic Pain Symptom Inventory (NPSI) and Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaires...
August 2, 2023: European Journal of Neurology
Patrícia Melo Sousa, Margarida Ferro, João Jacinto
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a recently recognised but underdiagnosed cause of late-onset hereditary ataxia. Symptoms may vary, and differential diagnoses can span several specialties. We report the case of a man in his 60 s who presented with a 10 year history of imbalance and progressive gait disturbance associated with a chronic spasmodic cough that preceded these symptoms by almost 30 years. He had previously undergone extensive testing for acquired and genetic causes of ataxia without a conclusive diagnosis...
July 25, 2023: BMJ Case Reports
Andreas Traschütz, Felix Heindl, Muhammad Bilal, Annette M Hartmann, Claudia Dufke, Olaf Riess, Andreas Zwergal, Dan Rujescu, Tobias Haack, Matthis Synofzik, Michael Strupp
BACKGROUND AND OBJECTIVES: Bilateral vestibulopathy (BVP) is a chronic debilitating neurologic disorder with no monogenic cause established so far despite familiar presentations. We hypothesized that replication factor complex subunit 1 (RFC1) repeat expansions might present a recurrent monogenic cause of BVP. METHODS: The study involved RFC1 screening and in-depth neurologic, vestibulo-oculomotor, and disease evolution phenotyping of 168 consecutive patients with idiopathic at least "probable BVP" from a tertiary referral center for balance disorders, with127 of them meeting current diagnostic criteria of BVP (Bárány Society Classification)...
September 5, 2023: Neurology
Natalia Dominik, Stefania Magri, Riccardo Currò, Elena Abati, Stefano Facchini, Marinella Corbetta, Hannah MacPherson, Daniela Di Bella, Elisa Sarto, Igor Stevanovski, Sanjog R Chintalaphani, Fulya Akcimen, Arianna Manini, Elisa Vegezzi, Ilaria Quartesan, Kylie-Ann Montgomery, Valentina Pirota, Emmanuele Crespan, Cecilia Perini, Glenda Paola Grupelli, Pedro J Tomaselli, Wilson Marques, Joseph Shaw, James Polke, Ettore Salsano, Silvia Fenu, Davide Pareyson, Chiara Pisciotta, George K Tofaris, Andrea H Nemeth, John Ealing, Aleksandar Radunovic, Seamus Kearney, Kishore R Kumar, Steve Vucic, Marina Kennerson, Mary M Reilly, Henry Houlden, Ira Deveson, Arianna Tucci, Franco Taroni, Andrea Cortese
Cerebellar Ataxia, Neuropathy and Vestibular Areflexia Syndrome (CANVAS) is an autosomal recessive neurodegenerative disease, usually caused by biallelic AAGGG repeat expansions in RFC1. In this study, we leveraged whole genome sequencing (WGS) data from nearly 10,000 individuals recruited within the Genomics England sequencing project to investigate the normal and pathogenic variation of the RFC1 repeat. We identified three novel repeat motifs, AGGGC (n=6 from 5 families), AAGGC (n=2 from 1 family), AGAGG (n=1), associated with CANVAS in the homozygous or compound heterozygous state with the common pathogenic AAGGG expansion...
July 14, 2023: Brain
Marios Hadjivassiliou, Riccardo Currò, Nick Beauchamp, Natalia Dominik, Richard A Grunewald, Priya Shanmugarajah, Panayiotis Zis, Nigel Hoggard, Andrea Cortese
BACKGROUND: Biallelic expansion of AAGGG in the replication factor complex subunit 1 ( RFC1 ) was identified as a major cause of cerebellar ataxia, neuropathy (sensory ganglionopathy, or SG) and vestibular areflexia syndrome (CANVAS). We wanted to clarify if RFC1 expansions can present with pure ataxia and if such expansions could be responsible for some cases where an alternative diagnosis had been made. METHODS: We identified patients with a combination of ataxia and SG and no other cause found, patients where an alternative diagnosis had been made, and patients with pure ataxia...
July 6, 2023: Journal of Neurology, Neurosurgery, and Psychiatry
David Pellerin, Carlo Wilke, Andreas Traschütz, Sara Nagy, Riccardo Currò, Marie-Josée Dicaire, Hector Garcia-Moreno, Mathieu Anheim, Thomas Wirth, Jennifer Faber, Dagmar Timmann, Christel Depienne, Dan Rujescu, José Gazulla, Mary M Reilly, Paola Giunti, Bernard Brais, Henry Houlden, Ludger Schöls, Michael Strupp, Andrea Cortese, Matthis Synofzik
BACKGROUND: Intronic GAA repeat expansions in the fibroblast growth factor 14 gene ( FGF14 ) have recently been identified as a common cause of ataxia with potential phenotypic overlap with RFC1 -related cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS). Our objective was to report on the frequency of intronic FGF14 GAA repeat expansions in patients with an unexplained CANVAS-like phenotype. METHODS: We recruited 45 patients negative for biallelic RFC1 repeat expansions with a combination of cerebellar ataxia plus peripheral neuropathy and/or bilateral vestibulopathy (BVP), and genotyped the FGF14 repeat locus...
June 30, 2023: Journal of Neurology, Neurosurgery, and Psychiatry
Swetha Tatineni, George Jarrouj, Christopher M Gomez, Brandon J Baird
OBJECTIVES: Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a common cause of late-onset ataxia that often presents with chronic cough. This study is the first to characterize the CANVAS cough both objectively and subjectively. METHODS: A cross-sectional study of 13 patients was conducted. Medical records and available esophagram, modified barium swallow study, esophageal manometry, and video laryngostroboscopy data were reviewed...
June 2023: Laryngoscope Investigative Otolaryngology
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