G Fernández-Eulate1,2, R Fernández-Torrón1,3, A Guisasola4, M T I Gaspar5, J Diaz-Manera6,7, M Maneiro1, M Zulaica3, V Olasagasti1, A F Formica1, J B Espinal1, M Ruiz8,9, A Schlüter8, A Pujol8,9,10, J J Poza1, A López de Munain1,3,11,12. 1. Department of Neurology, Donostia University Hospital, San Sebastian, Spain. 2. Reference Center for Neuromuscular Disorders, Pitié-Salpêtrière Hospital, Institute of Myology, Paris, France. 3. Neuromuscular Area, Group of Neurodegenerative Diseases, Biodonostia Health Research Institute, San Sebastian, Spain. 4. Department of Radiology, Osatek, San Sebastian, Spain. 5. Clinical Epidemiology Unit, Donostia University Hospital, San Sebastian, Spain. 6. Unitat de Malaties Neuromuscularis, Servei de Neurologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 7. John Walton Muscular Dystrophy Research Center, University of Newcastle, Newcastle, UK. 8. Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain. 9. Center for Biomedical Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Madrid, Spain. 10. Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain. 11. Neuroscience Department, School of Medicine of the University of the Basque Country, San Sebastian, Spain. 12. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto Carlos III, Madrid, Spain.
Abstract
BACKGROUND AND PURPOSE: BSCL2 heterozygote mutations are a common cause of distal hereditary motor neuropathies (dHMNs). A series of BSCL2 patients is presented and clinical, neurophysiological and muscle magnetic resonance imaging (MRI) findings are correlated. METHODS: Twenty-six patients from five families carrying the p.N88S mutation were identified. Age of onset, clinical phenotype (dHMN, Charcot-Marie-Tooth, spastic paraplegia), physical examination, disability measured as a modified Rankin Scale score and neurophysiological findings were collected. A whole body muscle MRI had been performed in 18 patients. The pattern of muscle involvement on T1-weighted and short time inversion recovery sequences was analysed. Hierarchical analysis using heatmaps and an MRI Composite Score were generated. Statistical analysis was carried out with STATA SE v.15 (TX, USA). RESULTS: The mean age was 51.54 ± 19.94 years and 14 patients were men. dHMN was the most common phenotype (50%) and five patients (19.23%) showed no findings on examination. Disease onset was commonly in childhood and disability was low (modified Rankin Scale score 1.34 ± 1.13) although median time since onset of disease was 32 years (range 10-47). Charcot-Marie-Tooth-like patients were more disabled and disability correlated with age. On muscle MRI, thenar eminence, soleus and tibialis anterior were most frequently involved, irrespective of clinical phenotype. MRI Composite Score was strongly correlated with disability. CONCLUSION: Patients with the p.N88S BSCL2 gene mutation are phenotypically variable, although dHMN is most frequent and generally slowly progressive. Muscle MRI pattern is consistent regardless of phenotype and correlates with disease severity, probably serving as a reliable outcome measure for future clinical trials.
BACKGROUND AND PURPOSE:BSCL2 heterozygote mutations are a common cause of distal hereditary motor neuropathies (dHMNs). A series of BSCL2patients is presented and clinical, neurophysiological and muscle magnetic resonance imaging (MRI) findings are correlated. METHODS: Twenty-six patients from five families carrying the p.N88S mutation were identified. Age of onset, clinical phenotype (dHMN, Charcot-Marie-Tooth, spastic paraplegia), physical examination, disability measured as a modified Rankin Scale score and neurophysiological findings were collected. A whole body muscle MRI had been performed in 18 patients. The pattern of muscle involvement on T1-weighted and short time inversion recovery sequences was analysed. Hierarchical analysis using heatmaps and an MRI Composite Score were generated. Statistical analysis was carried out with STATA SE v.15 (TX, USA). RESULTS: The mean age was 51.54 ± 19.94 years and 14 patients were men. dHMN was the most common phenotype (50%) and five patients (19.23%) showed no findings on examination. Disease onset was commonly in childhood and disability was low (modified Rankin Scale score 1.34 ± 1.13) although median time since onset of disease was 32 years (range 10-47). Charcot-Marie-Tooth-like patients were more disabled and disability correlated with age. On muscle MRI, thenar eminence, soleus and tibialis anterior were most frequently involved, irrespective of clinical phenotype. MRI Composite Score was strongly correlated with disability. CONCLUSION:Patients with the p.N88SBSCL2 gene mutation are phenotypically variable, although dHMN is most frequent and generally slowly progressive. Muscle MRI pattern is consistent regardless of phenotype and correlates with disease severity, probably serving as a reliable outcome measure for future clinical trials.