Περίληψη:
Objective: To perform phenotype and genotype characterization in myoclonus-dystonia patients and to validate clinical rating tools. Method: Two movement disorders experts rated patients with the Burke-Fahn-Marsden and Unified-Myoclonus rating scales using a video-recording protocol. Clinimetric analysis was performed. SGCE mutations were screened by Sanger sequencing and multiplex ligation-dependent probe amplification. Results: 48 patients were included and 43/48 rated. Mean age at assessment was 12.9±10.5 years (range 3–51) and 88% were ≤18 years of age. Myoclonus was a universal sign with a rostro-caudal severity-gradient. Myoclonus increased in severity and spread to lower limbs during action tests. Stimulus-evoked myoclonus was observed in 86.8% cases. Dystonia was common but mild. It had a focal distribution and was action-induced, causing writer's cramp (69%) and gait dystonia (34%). The severity of both myoclonus and dystonia had a strong impact on hand writing and walking difficulties. The Unified Myoclonus Rating scale showed the best clinimetric properties for the questionnaire, action myoclonus and functional subscales, and exceeded the Burke-Fahn-Marsden scale in its utility in assessing functional impairment in MDS patients. Twenty-one different SGCE mutations were identified in 45/48 patients, eleven being novel (most prevalent p. Val187*, founder mutation in Canary Islands). Conclusion: This study quantifies the severity of the motor phenotype in SGCE-myoclonus dystonia syndrome, with a special focus on children, and identifies disabilities in gross and fine motor tasks that are essential for childhood development. Our results contribute to the knowledge of SGCE-related MDS in the early stage of evolution, where disease-modifying therapies could be initiated in order to prevent long-term social and physical burdens. © 2020 Elsevier Ltd
Συγγραφείς:
Vanegas, M.I.
Marcé-Grau, A.
Martí-Sánchez, L.
Mellid, S.
Baide-Mairena, H.
Correa-Vela, M.
Cazurro, A.
Rodríguez, C.
Toledo, L.
Fernández-Ramos, J.A.
Pons, R.
Aguilera-Albesa, S.
Martí, M.J.
Eiris, J.
Iglesias, G.
De Fabregues, O.
Maqueda, E.
Garriz-Luis, M.
Madruga, M.
Espinós, C.
Macaya, A.
Cabrera, J.C.
Pérez-Dueñas, B.
Λέξεις-κλειδιά:
adolescent; adult; age; Article; Burke Fahn Marsden rating scale; child; clinical article; disease course; disease severity; dysgraphia; dystonia; female; gait disorder; gene; genetic screening; genotype; human; male; motor performance; multiplex ligation dependent probe amplification; myoclonus dystonia; phenotype; priority journal; rating scale; Sanger sequencing; SGCE gene; Unified Myoclonus rating scale; validation process; videorecording; walking difficulty; writer's cramp; child development; dystonic disorder; genetics; middle aged; motor performance; mutation; pathophysiology; phenotype; physiology; preschool child; severity of illness index; young adult, sarcoglycan; SGCE protein, human, Adolescent; Adult; Child; Child Development; Child, Preschool; Dystonic Disorders; Female; Humans; Male; Middle Aged; Motor Skills; Mutation; Phenotype; Sarcoglycans; Severity of Illness Index; Young Adult
