Charcot-Marie-Tooth disease and related neuropathies: Molecular basis for distinction and diagnosis

Cranial nerve involvement in CMT disease type 1 due to early growth response 2 gene mutation

“…10 The axonal subtype CMT2C is characterized by laryngeal recurrent and frenic nerve involvement 1,2 ; these nerves are rather long and progression of a length-dependent severe neuropathy might explain their involvement. 10 However, this mechanism cannot explain either oculomotor nerve palsy, which does not occur in CMT and DSD, or sensorineural hearing loss.…”

“…Micromutations involving the PMP22 gene or the myelin protein zero gene (MPZ) (CMT1B) are rarely found; the more common X-linked variety (CMTX) is associated with connexin-32 mutations. 1,2 In other cases, no mutation is found. Some families do not demonstrate linkage with any of these loci, providing evidence for the existence of another locus (CMT1C).…”

Diagnosis of hereditary neuropathies in adult patients

“…Moreover, there are diseases, such as Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to pressure palsies (HNPP), which present considerable expression variability and may go unrecognised in mildly affected family members. Apparently sporadic cases indeed often turn out to be familial when at-risk family members are carefully examined both clinically and electrophysiologically [88]. In acute porphyrias, the attacks occur only in a minority of disease carriers, while s Abstract This paper reviews the clinical diagnostic approach to hereditary neuropathies in adults by analysing: elements that point to a neuropathy of inherited origin, different modalities of presentation, laboratory and instrumental diagnostic tests, including molecular tests, symptoms and signs of involvement of other organs.…”

“…Severity is highly variable even within the same kinship, only rarely leading to severe impairment [34]. Subclassification of CMT into demyelinating (CMT1, accounting for about 2 / 3 of cases) and axonal (CMT2, about 1 / 3 ) varieties is based on nerve conduction velocities (NCV), while further subdivision depends on molecular genetics [27,48,88,99] (Table 2).…”

“…CMTX might represent up to 10 % of all CMT cases; it is characterised by absence of male-to-male transmission, and is more severe in affected males than in females both clinically and electrophysiologically [10,14,32,45]. The autosomal recessive forms of CMT, grouped under the term of CMT4, almost invariably have early onset and are more severe than the dominant types [27,88]. b) Electrophysiological examination is the next diagnostic step and is extremely important for orienting DNA analyses.…”