Mersiyanova et al. (2000) reported a large 6-generation family from Russia with autosomal dominant CMT2. Onset was in the second and third decade, characterized by difficulty in walking and weakness and atrophy of the distal lower limb muscles and a variable degree of deformity of the feet (pes cavus). Affected individuals did not exhibit enlarged nerves, ulcerated feet, hearing impairment, or paralysis of the vocal cords. Several patients had hyperkeratosis, although the association, if any, between the 2 disorders was not clear. The authors suggested the designation CMT2E for this disorder. 

Georgiou et al. (2002) described a large 5-generation Slovenian family with autosomal dominant CMT type 2E. Disease onset in most patients was in the first decade of life. The presenting symptoms were difficulty in walking or running, due to a slowly progressive distal weakness and wasting of the lower limbs. A steppage gait, pes cavus, and hammertoes were typically present. Over a period of 20 years after disease onset, two-thirds of patients developed upper limb involvement resulting in claw hands. All patients were ambulatory 20 to 30 years after onset. 

Fabrizi et al. (2004) reported a large kindred from southern Italy with autosomal dominant CMT2E spanning 5 generations and caused by mutation in the NEFL gene (162280.0002). An affected woman and her 2 affected sons had steppage gait, ataxic gait, peroneal muscular atrophy, decreased vibration sense with stocking and glove distribution, and hypotrophy of the hand muscles. One of the sons had claw hand deformities. Motor nerve conduction velocities (NCV) were decreased, consistent with a demyelinating neuropathy, but sural nerve biopsy of the mother showed a primary axonopathy characterized by giant axons containing disorganized neurofilaments. 

Miltenberger-Miltenyi et al. (2007) reported a large Austrian family in which at least 4 members had CMT2E confirmed by genetic analysis (162880.0006). Disease onset was in the second decade of life with pes cavus, progressive plantar extensor weakness, and distal lower limb atrophy and weakness. Two patients became wheelchair-bound. Affected members of a second Austrian family, with a different NEFL mutation (162280.0003), had disease onset before age 15 years in all but 1 patient. The disorder was slowly progressive but resulted in a severe and disabling phenotype. Electrophysiologic studies of both families showed intermediate motor nerve conduction velocities consistent with axonal pathology.
