The chronic degeneration of peripheral nerves and roots results in distal muscle atrophy beginning in the feet and legs and later involving the hands. The extensor hallucis and digitorum longus, the peronei, and the intrinsic muscles of the feet are affected early in life and this muscle imbalance produces the bony changes of pes cavus and pied en griffe (high arches and hammertoes). Later, all muscles of the legs and sometimes the lower third of the thigh become weak and atrophic. The thin legs have been likened to those of a stork or, if the lower thigh muscles are affected, to an inverted champagne bottle. Eventually the nerves to the calf muscles degenerate and the ability to plantar flex the feet is lost. After a period of many years, atrophy of the hand and forearm muscles develops in some cases. The hands later become clawed. The wasting seldom extends above the elbows or above the middle third of the thighs. Paresthesias and cramps are present but only to a slight degree and there is always some impairment, usually also mild, of deep and superficial sensation in the feet and hands, shading off proximally. Rarely, the sensory loss is severe and perforating ulcers appear as they do in the pure sensory varieties of inherited neuropathy. The tendon reflexes are absent in the involved limbs. The illness progresses very slowly over decades, giving the impression of stabilization for long periods.
Walking difficulty, which is ultimately the main disability, is caused by a combination of sensory ataxia and weakness. Foot-drop and instability of the ankles are additional handicaps. The feet and legs may ache after use and cramps may be troublesome as mentioned, but otherwise pain is unusual; the feet may become cool, swollen, and blue, secondary to inactivity of the muscles of the feet and legs and their dependent position. There is usually no disturbance of autonomic function. Fixed pupils, optic atrophy, and nystagmus and endocrinopathies, epilepsy, and spina bifida, which have been reported occasionally in association with peroneal muscular atrophy, probably represent coincidental congenital disorders. The only distinguishing clinical feature between types 1 and 2, and this is present in only a minority of cases, is perhaps enlargement of the nerves in type 1, most easily appreciated by palpation of the greater auricular and peroneal nerves. The clinical heterogeneity of CMT disease has been alluded to in the previous discussion and is evident in the numerous mutations that give rise to similar chronic polyneuropathies. Restricted forms are known to affect only the peroneal and pectoral or scapular muscles (scapuloperoneal form).
The differential diagnosis involves the distal muscular dystrophies, late forms of familial motor system disease, Friedreich ataxia, Roussy-Lévy syndrome (see later) and other familial polyneuropathies, and, in adult onset cases, CIDP and the paraproteinemic neuropathies, discussed earlier.
Electrophysiologic features Dyck and Lambert (1975) and Harding and Thomas (1980) are credited with subdividing CMT into the two broad types based on the speed of motor nerve conduction in the ulnar or median nerves, as mentioned, slow (mean conduction velocity less than 38 m/s but often in the range of 20 m/s) in type 1, and normal or near-normal conduction in CMT2. Electromyographers appropriately refer to these, respectively, as the demyelinating and axonal types. In both, the compound muscle action potentials and sensory potentials are greatly reduced in amplitude, but in type 2 there are findings of denervation in the EMG. In type 1 there is severe and widespread slowing of nerve conduction, but the electrical conduction block that characterizes acquired demyelinating neuropathies is not found and, in distinction to almost most all acquired diseases of peripheral nerves, the electrophysiologic findings, particularly the pronounced slowing of conduction in CMT1, are uniform throughout the peripheral nervous system.