Autonomic and respiratory dysfunction in Charcot-Marie-Tooth disease due to Thr124Met mutation in the myelin protein zero gene.
OBJECTIVE
To report the clinical and electrophysiological characteristics of a family presenting Charcot-Marie-Tooth disease (CMT) associated with autonomic nervous system disturbances.


METHODS
We studied nerve conduction values, postural adaptation, sympathetic skin reflex, the variation in heart rate by the Valsalva ratio and pupillometry in 7 members of a French family in which CMT due to a Thr124Met mutation in the myelin protein zero (MPZ) gene was diagnosed.


RESULTS
Clinical and laboratory evidence of autonomic nervous system disturbances were found in the affected individuals. The clinical phenotype was characterized by sensorimotor peripheral neuropathy, defined as axonal type by electrophysiological studies, and was associated with severe pain, bladder dysfunction, sudorimotor disturbances and abolished pupillary reflex to light. Moreover, two patients had severe restrictive respiratory insufficiency requiring noninvasive mechanical ventilation.


CONCLUSIONS
Our study demonstrates that autonomic disturbances may be one of the major clinical signs associated with CMT secondary to MPZ gene mutation in codon 124. Testing of pupillary reflex allows the discrimination of affected and unaffected subjects in our family. However, involvement of the autonomic nervous system in this type of neuropathy is unclear and further studies are required to elucidate the role of the MPZ gene in the autonomic nervous system.
Stojkovic
T
T
Department of Neurology, University of Lille, 59037 Lille, France. t-stojkovic@chru-little.fr
de Seze
J
J
Dubourg
O
O
Arne-Bes
M C
MC
Tardieu
S
S
Hache
J C
JC
Vermersch
P
P
D000328:Adult; D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000150:complications / Q000235:genetics*; D002607:Charcot-Marie-Tooth Disease / Q000150:complications / Q000235:genetics*; D004252:DNA Mutational Analysis; D005071:Evoked Potentials / Q000502:physiology; D005192:Family Health; D005260:Female; D005602:France; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D009132:Muscles / Q000502:physiology; D018993:Myelin P0 Protein / Q000235:genetics*; D009431:Neural Conduction / Q000502:physiology; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011680:Pupil / Q000502:physiology; D012120:Respiration Disorders; D012140:Respiratory Tract Diseases; D013912:Threonine / Q000235:genetics*; D001743:Urinary Bladder / Q000502:physiology
D018993:Myelin P0 Protein; D013912:Threonine; D008715:Methionine