I.06 Late onset forms of inherited neuropathies

Abstract

Hereditary neuropathies comprise a clinically and genetically very heterogenous group of neuromuscular disorders. The most common form, Charcot-Marie-Tooth disease (CMT, also known as motor and sensory neuropathy, HMSN), represents one of the most frequently inherited causes of neurological disability. Onset is usually in childhood, adolescence, or adulthood. The main phenotype is characterized by foot-deformities, symmetric, slowly progressive muscle weakness and wasting, and sensory deficits in the distal parts of upper and lower limbs. The underlying pathological event is demyelinating (CMT1) or axonal (primarily affecting axons, CMT2) nerve damage. Predominance of motor or sensory and/or autonomic symptoms has led to the diagnosis of distal hereditary motor neuropathies (dHMN) and hereditary sensory and autonomic neuropathies (HSN/HSAN). Research discoveries into the molecular causes of hereditary neuropathies has led to the identification of more than 80 disease genes. However, the underlying gene still remains undetermined in a considerable number of patients. An overview will be given about the most common genetic subtypes and phenotype-genotype correlations will be presented in selected cases. A particular focus will be on recent advances in the late-onset forms of hereditary neuropathies in which, by definition, age at disease onset is beyond 35 years.