Neuropathy

The genetic neuropathies are a clinically and genetically heterogeneous group of diseases that can broadly be classified into two groups: those in which the neuropathy is the sole or primary part of the disorder (Charcot-Marie-Tooth disease, CMT) and those in which the neuropathy is part of a more generalized neurologic or multisystem disorder (e.g., familial amyloid polyneuropathy, neuropathies associated with mitochondrial diseases, with hereditary ataxias, porphyrias). The former is the most common group, with a prevalence of 1 in 2500 people, and this chapter will concentrate on CMT. CMT is, however, an umbrella term that encompasses a wide variety of inherited sensory and/or motor neuropathies. The number of disease genes identified in CMT has expanded rapidly over the past few decades, making an accurate genetic diagnosis more challenging, although increasingly possible. Although no specific therapies are yet available, research into their pathogenesis has increased our understanding of the disease and allowed the development of rational approaches to therapy. In this chapter, the authors review the clinical features of CMT, suggest genetic testing strategies, and provide an update on new-generation sequencing techniques in inherited neuropathies.