Vocal cord paresis and diaphragmatic dysfunction are severe and frequent symptom

[Guest guest]

Vocal cord paresis and diaphragmatic dysfunction are severe and

frequent symptoms of GDAP1-associated neuropathy

http://brain.oxfordjournals.org/cgi/content/abstract/131/11/3051

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 unrelated 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.

[Guest guest]

I know this is just an abstract, but did they eliminate other possible causes,

e.g., severe allergies, GERD, etc.?

>

> (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.

>