Charcot-Marie-Tooth (CMT) is a genetically, clinically and electrophysiologically heterogeneous group of inherited disorders of the peripheral nervous system. The X-linked form of Charcot-Marie-Tooth disease (CMTX1) is the second most common cause of a demyelinating type of CMT. There are 6 types of CMTX (CMTX1-CMTX6). CMTX1 is the most common one, and is caused by mutations in the GJB1 gene which encodes connexin 32 (Cx32). Myelinating Schwann cells express Cx32, which likely forms gap junctions between the layers of myelin sheath. Gap junctions formed by Cx32 play an important role in the homeostasis of myelinated axons. CMTX1 is an X-linked dominant type of CMT with both demyelinating and axonal features. Affected males have moderate-to-severe symptoms, whereas heterozygous females are usually mildly affected, or even asymptomatic. Symptoms develop in late childhood, usually after the age of five in males, and later in affected females. The clinical phenotype is characterized by progressive distal muscle atrophy, weakness, sensory loss, areflexia, skeletal deformities (high arched feet), scoliosis and contractures. Clinical features also include involvement of hand muscles with pronounced atrophy, particularly affecting thenar muscles. Oligodendrocytes also express Cx32, so several patients have manifestations of central nervous system involvement or hearing impairment. Patients with CMTX1 typically manifest intermediate slowing of nerve conduction velocity (NCV). There is no known molecular-based treatments for CMTX1. Treatment is symptomatic and affected individuals are often evaluated and managed by a team of children neurologists, physiatrists, ortopedic surgeons and psychiatrist.