Phenotypic correlations in a large single‐center cohort of patients with BSCL2 nerve disorders: a clinical, neurophysiological and muscle magnetic resonance imaging 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.