1. RFC1 expansions are a common cause of idiopathic sensory neuropathy
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Emilia Bellone, Paola Mandich, Stefano Facchini, Giuseppe Cosentino, Anna Pichiecchio, Chiara Briani, Stefano Tozza, Enrico Marchioni, Lucio Santoro, Francesca Magrinelli, Stephanie Efthymiou, Aisling Carr, Marios Hadjivassiliou, Enrico Alfonsi, Chiara Gemelli, Natalia Dominik, Henry Houlden, Matilde Laura, Silvia Colnaghi, Enza Maria Valente, Mary M. Reilly, Alexander M. Rossor, Simone Gana, Pietro Businaro, Cristina Tassorelli, Adolfo M. Bronstein, Elisa Vegezzi, Marina Grandis, Diego Kaski, Elena Pegoraro, Nicholas J. Beauchamp, Riccardo Currò, Alessandro Salvalaggio, Francesca Castellani, Angelo Schenone, Hadi Manji, Valentina Galassi Deforie, Ilaria Callegari, Michael P. Lunn, Andrea Cortese, Fiore Manganelli, Currò, Riccardo, Salvalaggio, Alessandro, Tozza, Stefano, Gemelli, Chiara, Dominik, Natalia, Galassi Deforie, Valentina, Magrinelli, Francesca, Castellani, Francesca, Vegezzi, Elisa, Businaro, Pietro, Callegari, Ilaria, Pichiecchio, Anna, Cosentino, Giuseppe, Alfonsi, Enrico, Marchioni, Enrico, Colnaghi, Silvia, Gana, Simone, Valente, Enza Maria, Tassorelli, Cristina, Efthymiou, Stephanie, Facchini, Stefano, Carr, Aisling, Laura, Matilde, Rossor, Alexander M, Manji, Hadi, Lunn, Michael P, Pegoraro, Elena, Santoro, Lucio, Grandis, Marina, Bellone, Emilia, Beauchamp, Nicholas J, Hadjivassiliou, Mario, Kaski, Diego, Bronstein, Adolfo M, Houlden, Henry, Reilly, Mary M, Mandich, Paola, Schenone, Angelo, Manganelli, Fiore, Briani, Chiara, and Cortese, Andrea
- Subjects
Adult ,Male ,0301 basic medicine ,chronic idiopathic axonal polyneuropathy ,medicine.medical_specialty ,CANVAS ,RFC1 ,sensory neuropathy ,Aged ,DNA Repeat Expansion ,Female ,Humans ,Middle Aged ,Polyneuropathies ,Replication Protein C ,Cerebellar Ataxia ,Bilateral Vestibulopathy ,Chronic inflammatory demyelinating polyneuropathy ,Sensory system ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Subclinical infection ,Vestibular areflexia ,Cerebellar ataxia ,AcademicSubjects/SCI01870 ,business.industry ,Limb ataxia ,Peripheral Nervous System Diseases ,Original Articles ,medicine.disease ,Chronic cough ,030104 developmental biology ,Polyneuropathie ,AcademicSubjects/MED00310 ,Neurology (clinical) ,medicine.symptom ,business ,Polyneuropathy ,030217 neurology & neurosurgery ,Human - Abstract
After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that RFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy) from our general neuropathy clinics in Italy and the UK. All patients underwent full neurological evaluation and a blood sample was collected for RFC1 testing. Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy and in none with sensory-motor neuropathy. Forty-two per cent of RFC1-positive patients had isolated sensory neuropathy or sensory neuropathy with chronic cough, while vestibular and/or cerebellar involvement, often subclinical, were identified at examination in 58%. Although the sensory ganglia are the primary pathological target of the disease, the sensory impairment was typically worse distally and symmetric, while gait and limb ataxia were absent in two-thirds of the cases. Sensory amplitudes were either globally absent (26%) or reduced in a length-dependent (30%) or non-length dependent pattern (44%). A quarter of RFC1-positive patients had previously received an alternative diagnosis, including Sjögren’s syndrome, sensory chronic inflammatory demyelinating polyneuropathy and paraneoplastic neuropathy, while three cases had been treated with immune therapies., Currò et al. investigate the prevalence of RFC1 expansions in a cohort of patients with chronic idiopathic axonal polyneuropathy. RFC1 expansions were found in 34% of patients with sensory neuropathy, but in none with sensory-motor neuropathy. Clinical features and diagnostic clues that should lead to suspicion of RFC1 neuropathy are discussed.
- Published
- 2021
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