This relatively rare but striking neuropathy is inherited as an autosomal recessive trait. It begins in childhood or infancy, earlier than the typical form of peroneal muscular atrophy. Walking is delayed in onset and then progressively impaired. Pain and paresthesias in the feet are early symptoms, followed by the development of symmetrical weakness and wasting of the distal portions of the limbs. Talipes equinovarus postures with clawfeet and later clawhands are common. All modalities of sensation are impaired in a distal distribution, and the tendon reflexes are absent. Miotic, unreactive pupils, nystagmus, and kyphoscoliosis have been observed in some cases. The trunk and other cranial nerves are spared. The ulnar, median, radial, posterior tibial and peroneal nerves stand out like tendons and are easily followed with the gently roving finger. The enlarged nerves are not tender. Unlike other forms of hereditary neuropathy, the CSF protein is persistently elevated in Dejerine-Sottas disease, in all likelihood because the spinal roots are enlarged. Nerve conduction velocities are markedly reduced, even when there is little or no functional impairment. Patients are usually more disabled than those with peroneal muscular atrophy and are confined to wheelchairs at an early age. Treatment is purely symptomatic.
It is important to emphasize that the occurrence of hypertrophic neuropathy is not confined to this particular inherited disease. If one groups all patients in whom the nerves are diffusely enlarged (incorrectly called “hypertrophic” as it is mainly a nonspecific reaction of the epineural and perineural connective tissue that contributes to the bulk of the nerves), several diseases, both genetic and acquired, are included. The identifying histologic lesion in these cases is the “onion bulb,” which consists of a whorl of overlapping, intertwined, attenuated Schwann cell processes that encircle naked or finely myelinated axons and of endoneurial fibrofilaments. Enlarged nerves have been described in cases of recurrent demyelinating polyneuritis (CIDP), familial amyloidosis, Refsum disease, CMT type I, and other diseases. As was first pointed out by Thomas, any pathologic process that causes recurrent segmental demyelination and subsequent repair and remyelination may have this effect. In some patients with a history of early childhood hereditary polyneuropathy, the nerves are not yet palpably enlarged, but the characteristic Schwann cell abnormalities are revealed in biopsy material from a cutaneous nerve.
Phenotype-Genotype Correlations in the Inherited Sensorimotor Polyneuropathies