Neurologic findings in Machado-Joseph disease: relation with disease duration, subtypes, and (CAG)n.
BACKGROUND
Machado-Joseph disease (MJD), an autosomal dominant spinocerebellar degeneration caused by an expanded CAG repeat on chromosome 14q32.1, is a heterogeneous disorder for clinical manifestations. The reasons for the wide range of neurologic findings in this disease are poorly understood.


OBJECTIVE
To explain part of this heterogeneity through the association of the neurologic findings with sex, disease duration, age of onset, clinical type, and size of CAG repeat expansion.


METHODS
A case-control study.


METHODS
Ambulatory care.


METHODS
A consecutive sample of 62 patients with MJD.


METHODS
Neurologic signs.


RESULTS
A direct relationship was found between the disease duration and severity of gait and limb ataxia, dysarthria, dysphagia, fasciculations, pyramidal syndrome, and ophthalmoplegia (P<.02). The most severe forms of nuclear ophthalmoplegia were associated with type 1 MJD, whereas those of supranuclear ophthalmoplegia were associated with type 3 MJD (P<.001). It was also found that higher mean (CAG)(n) lengths were associated with worse degrees of the pyramidal syndrome and dystonia (P<.001). The presence and severity of nystagmus, eyelid retraction, rigidity and/or bradykinesia, and optic atrophy were not clearly associated with any of the predictive variables under study.


CONCLUSIONS
Disease duration can explain part of the heterogeneity of ataxia, dysarthria, dysphagia, fasciculations, pyramidal syndrome, and ophthalmoplegia, in MJD. Type 1 MJD was positively associated with nuclear ophthalmoplegia; type 3 MJD was positively associated with supranuclear ophthalmoplegia. Higher mean CAG lengths were found to correlate with the pyramidal syndrome and dystonia. Nystagmus, eyelid retraction, rigidity and/or bradykinesia, and optic atrophy were hardly attributable to any known reason or variable.
Jardim
L B
LB
MD, Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90035-003 Porto Alegre, Brazil. laurajardim@terra.com.br
Pereira
M L
ML
Silveira
I
I
Ferro
A
A
Sequeiros
J
J
Giugliani
R
R
D000328:Adult; D017668:Age of Onset; D000704:Analysis of Variance; D016022:Case-Control Studies; D003680:Deglutition Disorders / Q000209:etiology; D004401:Dysarthria / Q000209:etiology; D005260:Female; D020234:Gait Ataxia / Q000209:etiology; D006801:Humans; D017827:Machado-Joseph Disease / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012737:Sex Factors