Multisystemic <i>RFC1</i> -Related Disorder
Maria João Malaquias, Luís Braz, Cláudia Santos Silva, Joana Damásio, André Jorge, João Lemos, Catarina Falcão de Campos, Daniela Garcez, Miguel Oliveira Santos, Ana Graça Velon, André Caetano, Margarida Calejo, Preza Fernandes, Ângela Reis Rego, Sandra Castro, Ana Paula Sousa, Márcio Cardoso, Marco Fernandes, Miguel Pinto, Ricardo Taipa, Ana Lopes, Jorge Oliveira, Marina Magalhães, for RFC1 Repeat Expansion National Study Group
Abstract
Background and Objectives: -related patients. Methods: We retrospectively enrolled 67 RFC1-positive patients from multiple neurologic centers in Portugal. All patients underwent full neurologic and vestibular evaluation, as well as neuroimaging and neurophysiologic studies. For SNF and autonomic testing (n = 15), we performed skin biopsies, quantitative sensory testing, sudoscan, sympathetic skin response, heart rate deep breathing, and tilt test. Results: Multisystemic features beyond CANVAS were present in 82% of the patients, mainly chronic cough (66%) and dysautonomia (43%). Other features included motor neuron (MN) affection and motor neuropathy (18%), hyperkinetic movement disorders (16%), sleep apnea (6%), REM and non-REM sleep disorders (5%), and cranial neuropathy (5%). Ten patients reported an inverse association between cough and ataxia severity. A very severe epidermal denervation was found in skin biopsies of all patients. Autonomic dysfunction comprised cardiovascular (67%), cardiovagal (54%), and/or sudomotor (50%) systems. Discussion: spectrum can overlap not only with multiple system atrophy but also with hereditary motor and sensory neuropathy, hereditary sensory and autonomic neuropathy, and feeding dystonia phenotypes. Some clinical-paraclinical dissociations can pose diagnostic challenges, namely large and small fiber neuropathy and sudomotor dysfunction which are usually subclinical.