Vocal cord paresis and diaphragmatic dysfunction are severe and frequent symptom

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(Oral presentation at Antwerp Consortium July 2009)

Vocal cord paresis and diaphragmatic dysfunction are severe and frequent

symptoms of GDAPI-associated neuropathy.

T. Sevilla1,6, T. Jaijo2,7, D. Nauffae, D. Collado4, M.J. Chumillas5,6, J.J.

Vilchez1 ,6, N. Muelas1,6, L. BatallerI,6, R. Domenech3, C. Espin6s7and F.

Palau2,7

Departments of rNeurology, 3pneumology, 'Otolaryngology, 'Clinical

Neurophysiology, University Hospital La Fe, Valencia, Spain; 6CIBER de

Enfermedades Neurodegenerativas (CIBERNED), Valencia, Spain; 2Laboratory of

Genetics and Molecular Medicine. Instituto de Biomedicina de Valencia, CSIC,

Valencia, Spain; 'CIBER de

Enfermedades Rams (CIBERER), Valencia, Spain

Cranial nerve involvement in Charcot-Marie-Tooth disease (CMT) is rare, though

there are a number of CMT syndromes in which vocal cord paralysis is a

characteristic feature CMT disease due to mutations in the ganglioside-induced

differentiation-associated protein 1 gene

(GDAP1) has been reported to be associated with vocal cord and diaphragmatic

palsy.

In order to address the prevalence of these complications in patients with GDAP1

mutations we evaluated vocal cord and respiratory function in nine patients from

eight unelated families with this disorder. Hoarseness of the voice and

inability to speak loudly were reported by

eight patients and one had associated symptoms of respiratory insufficiency.

Patients were investigated by means of peripheral and phrenic nerve conduction

studies, flexible laryngoscopy, pulmonary function studies and polysomnography.

Nerve conduction velocities and pathological studies were compatible with axonal

CMT (CMT2) Flexible

laryngoscopy showed left vocal cord palsy in four cases, bilateral cord palsies

in four cases and was normal in one case.

Restrictive respiratory dysfunction was seen in the eight patients

with vocal cord paresis who were all chair-bound. These eight had confirmed

phrenic nerve dysfunction on neurophysiology evaluation. The patient with normal

vocal cord and pulmonary function had a less severe clinical course.

This study shows that CMT patients with GDAP1 mutations develop severe

disability due to weakness of limb muscles and that

laryngeal and respiratory muscle involvement occurs late in the disease process

when significant proximal upper limb weakness has developed. The early and

predominant involvement of the left vocal cord innervated by the longer left

recurrent laryngeal nerve

suggests a length dependent pattern of nerve degeneration. In GDAP1 neuropathy,

respiratory function should be thoroughly investigated because life expectancy

can be compromised due to respiratory failure.