Inherited peripheral neuropathies

Abstract

Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurologic or multisystem syndrome. Because of the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. This article reviews the biology of the inherited peripheral neuropathies, delineates major phenotypic features of the CMT subtypes, and suggest strategies for focusing genetic testing.

Figure 1

Schematic drawing of a neuron, its axon and Schwann cells with the major genes associated with Charcot-Marie-Tooth disease represented with their respective function and cellular compartment.

Figure 2

Algorithm for the genetic diagnosis of patients with Charcot-Marie-Tooth disease and slow (A) or very slow (B) upper extremity motor nerve conduction velocities. MNCV = motor nerve conduction velocity; PMP22 = peripheral myelin protein 22; dup = duplication; CMT = Charcot-Marie-Tooth disease; GJB1 = gap junction protein beta 1; Cx32 = Connexin 32; MPZ = myelin protein zero; LITAF = lipopolysaccharide-induced TNF factor; seq = sequencing; EGR2 = early growth response 2 From Saporta AS, Sottile SL, Miller LJ, et al. Charcot-Marie-Tooth disease subtypes and genetic testing strategies. Ann Neurol 2011; 69(1): 22 – 33; with permission

Figure 3

Algorithm for the genetic diagnosis of patients with Charcot-Marie-Tooth disease and intermediate (A) or normal (B) upper extremity motor nerve conduction velocities. MNCV = motor nerve conduction velocity;; CMT = Charcot-Marie-Tooth disease; GJB1 = gap junction protein beta 1; Cx32 = Connexin 32; MPZ = myelin protein zero; MFN2 = mitofusin 2; NEFL = neurofilaments light polypeptide; GDAP1 = ganglioside-induced differentiation-associated protein 1; GARS = glycyl-tRNA synthetase. From Saporta AS, Sottile SL, Miller LJ, et al. Charcot-Marie-Tooth disease subtypes and genetic testing strategies. Ann Neurol 2011; 69(1): 22 – 33; with permission.