Jardim L B, Pereira M L, Silveira I, Ferro A, Sequeiros J, Giugliani R
MD, Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90035-003 Porto Alegre, Brazil.
Arch Neurol. 2001 Jun;58(6):899-904. doi: 10.1001/archneur.58.6.899.
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.
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.
A case-control study.
Ambulatory care.
A consecutive sample of 62 patients with MJD.
Neurologic signs.
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.
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.
马查多-约瑟夫病（MJD）是一种常染色体显性遗传性脊髓小脑变性疾病，由14号染色体长臂32.1区的CAG重复序列扩增引起，临床表现具有异质性。目前对该疾病广泛的神经系统表现的原因了解甚少。
通过将神经系统表现与性别、病程、发病年龄、临床类型和CAG重复扩增大小相关联，来解释这种异质性的部分原因。
病例对照研究。
门诊护理。
连续选取62例MJD患者。
神经系统体征。
发现病程与步态和肢体共济失调、构音障碍、吞咽困难、肌束震颤、锥体束征和眼肌麻痹的严重程度之间存在直接关系（P<0.02）。最严重形式的核性眼肌麻痹与1型MJD相关，而上核性眼肌麻痹与3型MJD相关（P<0.001）。还发现较高的平均（CAG）n长度与锥体束征和肌张力障碍的严重程度较差相关（P<0.001）。眼球震颤、眼睑退缩、僵硬和/或运动迟缓以及视神经萎缩的存在和严重程度与所研究的任何预测变量均无明显关联。
病程可以解释MJD中共济失调、构音障碍、吞咽困难、肌束震颤、锥体束征和眼肌麻痹异质性的部分原因。1型MJD与核性眼肌麻痹呈正相关；3型MJD与上核性眼肌麻痹呈正相关。发现较高的平均CAG长度与锥体束征和肌张力障碍相关。眼球震颤、眼睑退缩、僵硬和/或运动迟缓以及视神经萎缩几乎无法归因于任何已知原因或变量。
