CHARCOT‐MARIE‐TOOTH WITH DIAPHRAGM AND VOCAL CORD PARALYSIS (CMT2C)

Abstract

Charcot‐Marie‐Tooth disease (CMT) is the most common inherited disorder of the peripheral nervous system and is clinically and genetically heterogeneous. Recent advances of molecular genetics has dramatically increased our understanding of the underlying disease mechanisms. Genetic linkage studies have identified a lot of genetic loci for different types of inherited neuropathies, although most genes involved still remain to be found. In fact, the axonal type of CMT associated with diaphragm and vocal cord paralysis (CMT2C) is not yet associated to a gene locus. We describe seven members affected by CMT2C belonging to a family expanded for three generations, and with a male‐to‐male transmission. Four patients, all affected by vocal cord paralysis (VCp) showed also distal weakness and atrophy more severely in the lower limbs. Three of these patients were treated surgically by arytenoidopexy for VCp, the last one with VCp and diaphragm paralysis was treated with cordectomy.Three other patients showed marked weakness and hypotrophy of upper and lower limbs. Two of these patients complained of laryngeal stridor and dispnoea during activity, the last one had neonatal diagnosis of SMA, but did not show respiratory impairment. All patients had pes cavus and absence of deep tendon reflexes. EMG examination showed clear neurogenic lesions in all the patients and in all the explored muscles. Conduction velocity (CV) studies showed an almost normal CV, while sensory‐ and motor‐evoked potentials had a severe amplitude reduction. Sural nerve biopsy performed in one patient showed clear signs of axonal degeneration.Our data confirm the association between VCp and axonal type of CMT, already described in isolated cases but only in two families in literature. We are trying to perform a linkage analysis in this family and we hope that this can help in understanding pathophysiologic mechanisms and the association between VCp and CMT.