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At a glance

Hereditary degenerative neurological disorder characterized primarily by peripheral motor nerves damage causing progressive muscle wasting, and affecting also sensitive and autonomic nervous components. The onset of the disease occurs during infancy or early childhood, and surely before the age of 3 years. The neuromuscular progression tends to be slow until the teenage years to, subsequently, accelerate with severe generalized disability. It is generally presumed that clinical course is severe, leading to wheelchair dependency at an early age. This form of neurodegeneration is more severe than observed in the other forms of Charcot-Marie-Tooth Disease.

Synonyms

Hypertrophic Neuropathy of Dejerine Sottas; Hereditary Motor and Sensory Neuropathy Type III (HMSN III); Dejerine-Sottas Neuropathy; Progressive Hypertrophic Interstitial Polyneuropathy of Childhood; Onion Bulb Neuropathy Syndrome; Charcot-Marie-Tooth Disease Type 3.

History

This medical condition was first described in 1893 by Joseph Jules Dejerine (1849-1917) and Jules Sottas (1866-1945), both French neurologists.

Incidence

The exact incidence for the Dejerine-Sottas Syndrome (DSS) remains unknown. Hereditary peripheral neuropathies constitute a large group of genetic diseases, with an overall prevalence of 1:2500. DSS belongs to the rare form of HMSN, considered Type III neuropathies, which suggests that the prevalence is much lower than reported for HMSN in general. This disorder is considered by most neurologists as one of five types of HMSN.

Genetic inheritance

It is inherited as autosomal dominant, although recent evidence suggests that is can also be autosomal recessive. The phenotype is genetically heterogeneous. The condition is caused by mutations in a various genes (MPZ, Peripheral Myelin Protein 22 [PMP22], PRX and Early Growth Response protein 2 [EGR2]) that affects proteins involved in the formation of axons and the myelin. It involves especially chromosome 8. Currently, this disease has no known cure.

Pathophysiology

Interstitial hypertrophic neuropathy with abnormal myelin.

Diagnosis

Usually, the nerve enlargements lead to palpable nerves by age 3 to 5 years. Cranial nerve or spinal nerve root enlargement (hypertrophy) giving to the nerves an appearance of “onion bulb” on MRI or myelography. Electromyography studies show significant reduction in the excitability and conduction speed of the peripheral and possibly cranial nerves. Motor nerve conduction velocities are reported below 12 m/sec. Elevated levels of cerebrospinal fluid protein are common. Ultimately, genetic mapping and nerve biopsy confirm the diagnosis. The histology shows onion bulb aspects of nerve sheets.

Clinical aspects

Clinical manifestations begin in early infancy and are rapidly progressive. The course is characterized by exacerbations and remissions. They begin with distal muscular weakness, followed by gait disturbances, deformities of feet, kyphoscoliosis, and fasciculations. There is a distal sensory loss of all four extremities with incoordination of the arms and areflexia. Pupillary reflex is often blunted. Clinical differentiation between ...

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