Spinal Charcot-Marie-Tooth disease: a reappraisal

Université Lyon I, Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Centre de Référence Maladies Neuromusculaires Rares, Lyon, France.
Muscle & Nerve (Impact Factor: 2.28). 10/2012; 46(4):604-9. DOI: 10.1002/mus.23456
Source: PubMed


Distal hereditary motor neuropathy (dHMN) is characterized by isolated distal muscle atrophy without sensory deficit. Nevertheless, clinical sensory loss has been reported despite preserved sensory nerve conduction in a few patients, thus differentiating these cases from the classical type 2 Charcot-Marie-Tooth disease (CMT2).

We report 4 patients who presented with clinical sensory and motor neuropathy and normal peripheral sensory nerve conduction studies and were investigated with complete electrophysiological studies, including somatosensory evoked potentials (SEP).

These patients had a clinical presentation of classical CMT with isolated axonal motor neuropathy suggestive of dHMN. Interestingly, tibial nerve SEPs showed abnormalities suggestive of proximal involvement of dorsal roots that may explain the clinical somatosensory disturbances.

These cases support the concept of spinal CMT that should be recognized as an intermediate form between dHMN and CMT2. SEP recording was helpful in defining a more precise phenotype of spinal CMT.

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    • "5.3.2. Distal hereditary motor neuropathy, spinal Charcot-Marie- Tooth disease, or distal spinal muscular atrophy Distal hereditary motor neuropathy (dHMN), also referred to as distal SMA or spinal CMT, represents a group of clinically and genetically heterogeneous diseases caused by degeneration of spinal motor neurons (Devic et al., 2012; Rossor et al., 2012). Spinal CMT is defined by a slowly progressive, symmetrical, predominantly distal lower motor neuron phenotype. "
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    ABSTRACT: This review focuses on recent advances in the diagnostic approaches and the underlying pathophysiological mechanisms of Charcot-Marie-Tooth (CMT) disease. We also discuss the emerging therapies for this hereditary neuropathy. To date, numerous genes are implicated in CMT, and new genes have recently been found to be associated with this neuropathy (INF2, FBLN5, etc.). Some specific or evocative clinical signs of CMT subtypes (proteinuria with INF2 mutations, etc.) have been identified. Characteristic pathological findings, which may suggest gene mutations, are also recognized by nerve biopsy (mainly ultrastructural lesions). CMT disease is the most common inherited neuromuscular disorder, with a fairly homogeneous clinical phenotype (progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, and depressed tendon reflexes). With more than 40 genes implicated, an update of the present and rather confusing classification of CMT is needed. Over the last few years, new mutated genes have been discovered. Although nerve biopsy is not routinely carried out in CMT neuropathies, it may show characteristic features, which can orientate the search for the mutated gene. There are currently no effective medications for CMT, but clinical trials are ongoing or planned.
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