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The RBM20 gene encodes the muscle-specific splicing factor RNA-binding motif 20, a regulator of heart-specific alternative splicing. Nearly 40 potentially deleterious variants in RBM20 have been reported in the last ten years, being found to be associated with highly arrhythmogenic events in familial dilated cardiomyopathy. Frequently, malignant arrhythmias can be a primary manifestation of disease. The early recognition of arrhythmic genotypes is crucial in avoiding lethal episodes, as it may have an impact on the adoption of personalized preventive measures. Our study performs a comprehensive update of data concerning rare variants in RBM20 that are associated with malignant arrhythmogenic phenotypes with a focus on personalized medicine. Yes

Introducción La mutación genética Val30Met de la proteína transtiretina (TTR) es causante de la polineuropatía amiloidótica familiar, comprometiendo en fases iniciales las fibras nerviosas pequeñas (mielinizadas Aδ y amielínicas tipo C), involucradas en funciones autonómicas, nocicepción, percepción térmica y sudoración. Los métodos neurofisiológicos convencionales, no logran detectar dichas anormalidades, retardando el inicio de tratamientos específicos para la enfermedad. Metodología El objetivo principal fue evaluar el test de cuantificación sensitiva (QST) como método de detección temprana de anormalidades de fibra pequeña, en individuos Val30Met, seguidos en el Hospital Universitario Santa María, Lisboa. Se clasificaron los pacientes en 3 grupos, según sintomatología y examen neurológico. Se analizaron los umbrales para percepción de frío, dolor con el calor y vibración en los grupos, en correlación con controles sanos. Resultados 18 registros de controles sanos y 33 de individuos con la mutación, divididos en asintomáticos (24,2%), sintomáticos con examen neurológico normal (42,4%) y sintomáticos con examen neurológico anormal (33,3%). No se encontraron diferencias entre los pacientes asintomáticos y los controles. Los umbrales para frío (p=0,042) y en el dolor intermedio con el calor (HP 5) (p=0,007) se encuentran elevados en individuos Val30Met sintomáticos con examen normal. En los pacientes sintomáticos con alteraciones al examen, también se presentaron alteraciones en el intervalo entre el inicio y el dolor intermedio con el calor (HP 5-0,5) (p=0,009). Discusión Los umbrales de frío y de percepción de dolor con el calor, permiten detectar anormalidades en personas con la mutación TTR Val30Met, sintomáticos, incluyendo aquellos sin cambios objetivos al examen neurológico. Introduction The small fiber neuropathies alter myelinized Aδ fibers and non-myelinized type C fibers, involved in autonomic functions, nociception, thermal perception and sweating. Genetic mutation TTR-Val30Met a most common etiology of Familial Amyloid Polineuropathy, compromised earlier the small nerve fibers. Conventional neurophysiological studies are unable to detect those abnormalities, delaying specific treatments. Methods The main goal of the present study was to evaluate the Quantitative Sensory Testing –QST, as an early diagnostic tool, identifying abnormalities in patients with the genetic mutationVal30Met in transthyretin (TTR) gene, followed at Santa María Hospital, Lisbon, Portugal. Patients were classified in 3 groups according to symptoms and neurological examination. Thresholds for cold perception, heat-pain and vibration were assessed in the different groups, compared to healthy controls. Results 33 cases and 18 controls, divided in asymptomathic (24.2%), symptomatic with normal neurological examination (42.4%) and symptomatic with abnormal neurological examination (33.3%). There were no differences between asymptomatic patients and healthy controls. The abnormalities on cold threshold detection (p=0,042) and intermediate severity of heat-pain response (HP5) (p=0,007), can occur before changes in the neurological examination. In patients with abnormal neurological examination differences also include the stimulus-response slope (HP 5-0,5) between intermediate severity (HP 5.0) and onset perception of pain with heat (HP 0.5) (p=0,009). Discussion The Quantitative Sensory Testing showed to be a useful tool in the detection of earlier abnormalities in patients withTTR Val30Met mutation. International Federation of Clinical Neurophysiology