Phenotypic correlations in a large single center cohort of patients with BSCL2 nerve disorders: a clinical, neurophysiological and muscle MRI study

Abstract

Background: BSCL2 heterozygote mutations are a common cause of distal hereditary motor neuropathies (dHMN). We present a series of BSCL2 patients and correlate clinical, neurophysiological and muscle-MRI findings. Methods: 26 patients from 5 families carrying the p.N88S mutation were ascertained. Age of onset, clinical phenotype (dHMN, Charcot-Marie-Tooth/CMT, spastic paraplegia), physical examination, disability measured as modified Rankin score (mRS) and neurophysiological findings were collected. A whole body muscle-MRI had been performed in 18 patients. We analyzed the pattern of muscle involvement on T1-weighted and STIR sequences. Hierarchical analysis using heatmaps and a MRI Composite Score (MRI CS) were generated. Statistical analysis was carried out with STATA SE v.15. Results Mean age was 51.54+/-19.94 years and 14 patients were males. dHMN was the most common phenotype (50%) and 5 patients (19.23%) showed no findings on examination. Disease onset was commonly in childhood and disability was low (mRS=1.34+/-1.13) although median time since onset of disease was 32 years (range=10-47). CMT-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 CS 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.