Hereditary, non HINT1 related, axonal neuropathy with neuromyotonia

To date, neuromyotonia in the context of an inherited axonal neuropathy has been linked to autosomal recessive mutations in the histidine triad nucleotide binding protein 1 (HINT1) gene. In this study we describe two unrelated male patients with late-onset, predominantly motor, axonal neuropathy with neuromyotonia, who carried an autosomal dominant c.103G > A mutation in the myelin protein zero (MPZ) gene (NM_000530.8:c.103G > A, p.Asp35Asn), identified by whole-exome sequence analysis (WES). CASE DESCRIPTIONS: The first patient presented progressive leg muscle weakness and stiffness with difficulty in walking, pain and increased creatine kinase levels,during his fifth decade of life. Electrophysiological examination revealed findings of an axonal, length-dependent polyneuropathy with spontaneous activity, mainly neuromyotonia. Over the 20-year disease course since the first reported symptoms, muscle weakness gradually worsened and he is currently unable to walk without assistance. A second male patient, unrelated to the first one, showed similar clinical and electrophysiological features of a length-dependent axonal neuropathy with neuromyotonia. WES detected the same MPZ missensevariant. CONCLUSION: This study suggests a novel entity in the spectrum of Charcot-Marie-Tooth hereditary neuropathies, characterized by autosomal dominant axonal neuropathy with neuromyotonia (AD-NMAN).