A Practical Approach to the Genetic Neuropathies
An acute or subacute onset, patchy neuropathy with conduction block strongly suggests an acquired demyelinating neuropathy, such as chronic inflammatory demyelinating polyradiculoneuropathy. Over the last 5 years, however, it has been recognised that for a handful of genetic types of CMT (GJB1, MPZ, SH3TC2, SPTLC1 and FIG4) the neurophysiology may suggest an acquired inflammatory neuropathy. This is most commonly encountered for CMTX1 due to mutations in GJB1 and should be considered in patients with treatment-resistant chronic inflammatory demyelinating polyradiculoneuropathy.
Other clinical markers that can help to differentiate genetic from acquired neuropathies include asymmetric weakness, cerebrospinal fluid (CSF) fluid examination and MRI of nerve roots. While these remain useful diagnostic tools, they are not absolute. For example, up to 7% of patients with CMT1A have a minor degree of asymmetry. Similarly, a CSF protein of up to 1 g/L (but not >2 g/L) and the presence of thickened nerve roots may occur in genetic demyelinating neuropathies such as CMT1A.
If one takes a detailed history, almost all cases of CMT have a chronic and progressive course. The one exception is CMT due to homozygous or compound heterozygous mutations in FIG4 in which patients may develop acute weakness and wasting of one limb resembling motor neurone disease (often on the background of a chronic demyelinating neuropathy).
Chameleons
An acute or subacute onset, patchy neuropathy with conduction block strongly suggests an acquired demyelinating neuropathy, such as chronic inflammatory demyelinating polyradiculoneuropathy. Over the last 5 years, however, it has been recognised that for a handful of genetic types of CMT (GJB1, MPZ, SH3TC2, SPTLC1 and FIG4) the neurophysiology may suggest an acquired inflammatory neuropathy. This is most commonly encountered for CMTX1 due to mutations in GJB1 and should be considered in patients with treatment-resistant chronic inflammatory demyelinating polyradiculoneuropathy.
Other clinical markers that can help to differentiate genetic from acquired neuropathies include asymmetric weakness, cerebrospinal fluid (CSF) fluid examination and MRI of nerve roots. While these remain useful diagnostic tools, they are not absolute. For example, up to 7% of patients with CMT1A have a minor degree of asymmetry. Similarly, a CSF protein of up to 1 g/L (but not >2 g/L) and the presence of thickened nerve roots may occur in genetic demyelinating neuropathies such as CMT1A.
If one takes a detailed history, almost all cases of CMT have a chronic and progressive course. The one exception is CMT due to homozygous or compound heterozygous mutations in FIG4 in which patients may develop acute weakness and wasting of one limb resembling motor neurone disease (often on the background of a chronic demyelinating neuropathy).
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