Hereditary demyelinating motor and sensory neuropathy

The demyelinating hereditary motor and sensory neuropathies (HMSN) are a group of inherited progressive neuropathies with markedly decreased nerve conduction velocity and chronic segmental demyelination in the peripheral nerve. Inheritance is autosomal dominant (AD) or autosomal recessive (AR). Autosomal dominant demyelinating HMSN (AD HMSN type I) is genetically heterogeneous and at least three different gene loci have been identified: a locus on chromosome 17 (HMSN Ia), a locus on chromosome 1 (HMSN Ib) and a locus not linked to chromosome 17 or 1 (HMSN nonIa-nonIb). HMSN type Ia is the most common form of AD HMSN. Recently, it has been demonstrated that the HMSN Ia phenotype results either from a duplication of chromosome 17p11.2 or from a point mutation in the peripheral nerve-specific PMP-22 gene which is located in the duplication. Pathology of type Ia is dominated by chronic segmental demyelination with classical onion bulbs. Autosomal recessive demyelinating HMSN shows a broad spectrum of pathological features. The genetic defect or defects are not yet known. On the basis of morphological characteristics we were able to discern four subtypes. Two AR subtypes are clinically and electrophysiologically comparable to AD HMSN type I, namely AR HMSN type I with basal lamina onion bulbs and AR HMSN type I with focally folded myelin. Two AR subtypes with amyelination, respectively or hypomyelination of the peripheral nerves are also more severely affected both clinically and electrophysiologically and could be designated as HMSN type III. A third condition with a HMSN type III phenotype shows mainly classical onion bulbs in peripheral nerves, but the inherited nature of this disorder is uncertain and identical features have been described in steroid-responsive inflammatory demyelinating neuropathy. The morphologically based subtypes of AR demyelinating HMSN may represent different genetic disorders, allelic differences or phenotypic variations.