Demyelinating CMT–what’s known, what’s new and what’s in store?

• Charcot–Marie–Tooth disease is common affecting 1 in 2500 people.
• Demyelination is observed in two major groups – CMT1 and CMT4.
• CMT1A remains the most commonly described CMT across all populations.
• CMT4 is typically severe with early onset and associated features, such as scoliosis.
• Recent molecular advances have improved our understanding of demyelinating CMT.

Inherited neuropathies known collectively as Charcot–Marie–Tooth disease are one of the most common inherited neurological conditions affecting ∼1 in 2500 people. A heterogenous disorder, CMT is divided into subtypes based on the pattern of inheritance and also by neurophysiological studies. Despite the clinical similarities among patients with demyelinating CMT, it is recognized that this group of disorders is both genetically and phenotypically heterogenous.Understanding the pathogenesis of these disorders requires an intimate knowledge of normal myelin development and homeostasis. Improvements in genetic testing techniques over the last 20 years have contributed majorly to the identification of specific genes, proteins, and molecular pathways that are providing the basis for understanding the disease processes and developing rational approaches to therapy.