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The inherited neuropathies are a large heterogeneous group which can be divided into those where the neuropathy is the sole or primary part of the disease, and those where it is part of a more widespread neurological or multisystem disorder (table 1). Here I will concentrate on the former group, especially Charcot-Marie-Tooth (CMT) disease and related disorders, with a particular emphasis on the diagnostic approach from a practising clinician’s perspective.
CHARCOT-MARIE-TOOTH DISEASE AND RELATED DISORDERS
Charcot-Marie-Tooth disease is not so much a single disease as a clinically and genetically heterogeneous group of inherited neuropathies, but for simplicity all types of CMT will just be referred to as CMT throughout this review. They are relatively common with an overall prevalence of 1 in 2500.1 CMT is also referred to as hereditary motor and sensory neuropathy (HMSN) but CMT is the preferred term.
CMT is characterised clinically by distal muscle wasting and weakness, reduced tendon reflexes, impaired distal sensation and variable foot deformity, and neurophysiologically by a motor and sensory neuropathy. There is a wide variation in the age of onset and severity, depending to a large extent on the underlying genetic defect. Traditional clinical classifications differentiate between:
CMT, with its clear motor and sensory involvement;
hereditary sensory and autonomic neuropathy (HSAN), with much more sensory and autonomic but fewer motor features; and
distal hereditary motor neuropathy (dHMN), which is only motor.
However, recent genetic findings have shown that certain forms of CMT and HSAN are very difficult to distinguish clinically despite being caused by mutations in different genes, and certain recently described genes for axonal CMT also cause forms of dHMN—that is, the same phenotype can be caused by different genes, and the same gene can cause different phenotypes. As there have now been more than 30 causative genes described …
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