Charcot‐Marie‐Tooth disease type 1A: clinicopathological correlations in 24 patients

Abstract

We examined nerve biopsies from 24 patients with Charcot-Marie-Tooth disease type 1A (CMT1A) and proven 17p11.2-12 duplication. There were seven males and 17 females with a mean age of 27.85 +/- 18.95 years at the time of nerve biopsy. A family history consistent with dominant inheritance was present in 17 patients. Clinical features were classical in 16 patients and were atypical in the other eight: one had calf hypertrophy; two had Roussy-Levy syndrome; one had had a subacute inflammatory demyelinating polyneuropathy 11 years earlier and presented a relapse on the form of a chronic inflammatory demyelinating polyneuropathy; one had carpal tunnel syndrome; one had a recent painful neuropathy in both legs; and two had chronic inflammatory demyelinating polyneuropathy. Onion bulb formations (OMFs) were present in every case and most of them were characteristic, whereas burnt-out or cluster-associated OMFs were less common. Depletion of myelinated fibers was severe in 20 cases (169-2927/mm2) and varied from 5187 to 3725/mm2 in three children (4-9 years old). In addition, features of macrophage-associated demyelination were observed in the last four atypical cases. Known for more than 20 years, inflammatory demyelination superimposed in the course of CMT1A has been reported in a few cases in the past few years, mainly concerning asymptomatic or atypical patients. Such an association deserves to be better known because corticotherapy improves weakness in most of these patients.

Evidence for macrophage‐mediated myelin disruption in an animal model for Charcot‐Marie‐Tooth neuropathy type 1A

“…Most of these patients, however, share some common clinical features with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), such as asymmetry, sudden worsening, and pain, which are not typical for CMT1. A recent report on CMT1A patients with approved PMP22 duplication demonstrates a relatively high proportion of cases that show macrophage‐related demyelination in nerve biopsies (Carvalho et al, 2005). Three patients share at least one of the CIDP‐like features or were of early onset (Carvalho et al, 2005).…”

PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

“…In some cases the tremor can be quite severe. Several CMT1A patients with tremor are described as having a Roussy-Lévy phenotype [26,43,44]. However, the original Roussy-Lévy family carried a mutation in the MPZ gene [45].…”

“…Only rarely patients have normal reflexes, mostly they are absent (in up to 46-75% of patients) or depressed [26-29]. Hypertrophy of nerves is a feature of CMT1A, rarely clinically present and mostly established by pathology [44] or imaging studies [50-53]. …”

“…The mean g-ratio (axon diameter versus fibre diameter) is significantly lower than normal [63]. Characteristic onion bulb formation occurs after the age of six [44,63-65]. Axonal loss is also found in childhood [65].…”

Electrophysiological Evaluation of Chronic Inflammatory Demyelinating Polyneuropathy and Charcot-Marie-Tooth Type 1: Dispersion and Correlation Analysis

“…CMT type 1 (CMT 1), which is the most common type of CMT, is characterized by demyelinating neuropathy that invades both motor nerves and sensory nerves18 ) . In most cases, CMT 1 is attributable to the duplication and point mutation of the PMP-22 gene19 ) . Although genetic testing is essential to confirm CMT 1, electrodiagnostic evaluations conducted prior to testing can prove useful in genetic counseling, the selection of subjects or candidate genes in molecular genetic studies, and the identification of patients with no symptoms20,21,22,23 ) .…”