Dejerine-Sottas Syndrome (DSS)
Incidence
DSS is inherited in an autosomal dominant pattern with two identified molecular causes and a suspected third locus. Many patients with DSS appear to represent sporadic cases that were believed to be of an autosomal recessive etiology.
Clinical Characteristics
Clinical Features resemble Charcot-Marie-Tooth (CMT) disease. DSS is more severe than CMT and usually has an infantile or childhood onset of symptoms. The clinical features overlap with those of CMT type 1. They are, however, more toward the spectrum of congenital hypomyelinating neuropathy. Clubfoot may also be present at birth or children may present with delayed motor milestones and deformity of the feet and lower limbs. Muscle fasciculations usually begin in the legs and progress to other muscles. There may be cranial and spinal nerve involvement leading to nystagmus, miosis, and a Romberg sign. Distal sensory abnormalities usually develop in all four extremities. Electrophysiologic studies show symmetric and uniform abnormalities. The slowing of the NCVs is greater than in CMT type 1. Cerebrospinal fluid analysis often demonstrates elevated protein. Peripheral nerve biopsy shows increased size and they are firm and gelatinous. Microscopic examination may show only rare nerve fibers to contain myelin and hypertrophic changes with "onion bulb" formations. Molecular genetic studies have shown DSS to be caused by mutations in two of the genes also responsible for CMT type 1. Point mutations and small insertions or deletions have been found in myelin protein zero on chromosome 1q21.2-q33 as a cause of DSS in some patients. Point mutations have been identified in peripheral myelin protein 22 (PMP22) on chromosome 17p11.2 of other patients . There has also been suggestion of an additional locus on chromosome 8q23-q24. However, significant evidence has not been published.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
Distal sensory abnormalities usually develop in all four extremities. Electrophysiologic studies show symmetric and uniform abnormalities. The slowing of the NCVs is greater than in CMT type 1. Cerebrospinal fluid analysis often demonstrates elevated protein. Peripheral nerve biopsy shows increased size and they are firm and gelatinous. Microscopic examination may show only rare nerve fibers to contain myelin and hypertrophic changes with "onion bulb" formations.