Pathologic findings Degenerative changes in the nerves result in depletion of the population of large sensory and motor fibers, leaving only the condensed endoneurial connective tissue. As far as one can tell, axons and myelin sheaths are both affected, the distal parts of the nerve more than the proximal ones. In type I, the nerves may be enlarged, with “onion-bulb” formations of Schwann cells and fibroblasts, as in Dejerine-Sottas disease (CMT3; type III HMSN in the Dyck classification). This change can often be seen in sural nerve biopsies. Anterior horn cells are slightly diminished in number and some are chromatolyzed as a secondary change. Dorsal root ganglion cells suffer a similar fate. The disease involves sensory posterior root fibers with degeneration of the posterior columns of Goll more than of Burdach. The autonomic nervous system remains relatively intact. The muscles contain large fields of atrophic fibers (group atrophy). Some of the larger fibers have a target appearance and may show degenerative changes. All these muscle changes are typical of neurogenic denervation. Former claims of a coincidental myelopathy and degeneration of spinocerebellar and corticospinal tracts probably indicate that the associated disease was really Friedreich ataxia or some other combination of chronic myelopathy and neuropathy.
Treatment No specific treatment is known. Stabilizing the ankles by arthrodeses is indicated if foot-drop is severe and the disease has reached the point where it is not progressing. Pediatric orthopedic specialists have experience with several techniques to stabilize the joints of weakened limbs. Regular exercise, but avoiding excessive weight training, is usually prescribed. In mild and early cases, fitting the legs with light braces and the shoes with springs to overcome foot-drop can be helpful.
(HNPP, PMP22 Deletion)
This unusual but distinctive process of multiple recurrent local neuropathies, first reported by Earl and colleagues, is caused by a deletion of the PMP22 gene, the one that is duplicated in the previously described CMT1A. In both CMT1A and hereditary neuropathy with pressure palsies (HNPP), the PMP22 gene is functionally normal and these disorders arise because the total amount of the protein is abnormal. In CMT1A the gene is duplicated on one chromosome, thereby increasing the total PMP22 protein; by contrast, in HNPP, the gene is deleted so that the PMP22 protein is at approximately half-normal levels. HNPP is transmitted as a dominant trait. In these individuals, the focal neuropathies and plexopathies are generally not painful (in contrast with related conditions of hereditary neuralgic amyotrophy discussed further on). Focal nerve lesions are often provoked by slight or even brief compression. In addition to recurrent focal nerve palsies, most individuals with HNPP have an underlying chronic but slowly progressive demyelinating sensorimotor neuropathy that is mild on clinical examination (e.g., not all cases show areflexia). Electrophysiologic studies are abnormal, but may be only subtly so, with some slowing of conduction and distal motor and sensory nerve abnormalities, particularly across sites of compression. Nerve biopsies from these patients are most remarkable for the presence of localized nerve sheath thickening with duplication of the myelin lamellae (so-called tomaculae, meaning sausage shaped).
Hypertrophic Neuropathy of Infancy (Dejerine-Sottas Disease, Congenital Hypomyelination, CMT3)