Myelin protein zero mutation His39Pro: Hereditary motor and sensory neuropathy with variable onset, hearing loss, restless legs and multiple sclerosis

Background: Mutations of myelin protein zero (MPZ) may cause inherited neuropathy with variable expression. Objective: To report phenotypic variability in a large American kindred with MPZ mutation His39Pro. Patients: Genetic testing was performed on 77 family members and 200 controls. Clinical and electrophysiological field study assessments were available for review in 47 family members. Results: His39Pro was found in all 10 individuals prospectively identified with neuropathy. 200 normal controls were without mutation. Symptoms of neuropathy began in adulthood and were slowly progressive except for one acute-onset painful sensory neuropathy. Associated features included premature hearing loss (n=7), nocturnal restless leg symptoms (n=8) and multiple sclerosis in one. Conclusions: MPZ mutation His39Pro may be associated with acute-onset neuropathy, early-onset hearing loss and restless legs. The relationship with multiple sclerosis in the proband remains uncertain.