Fragile X-associated tremor/ataxia syndrome: clinical phenotype, diagnosis, and treatment.
Fragile X-associated tremor/ataxia syndrome: clinical phenotype, diagnosis, and treatment.
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DOI：
10.2310/jim.0b013e3181af59c4
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发表时间：
2009-12
期刊：
影响因子：
--
通讯作者：
Leehey MA
中科院分区：
文献类型：
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作者：
Leehey MA
脆性X相关性震颤/共济失调综合征（FXTAS）是由脆性X智力低下1基因中前突变范围（55-200）内的CGG重复扩增引起的神经退行性疾病。通常在70岁出头发病，主要受影响的是男性。主要体征为小脑步态共济失调、意向性震颤、额叶执行功能障碍和全脑萎缩。其他常见的发现是帕金森综合征（轻度）、周围神经病变、精神症状（抑郁、焦虑、激越）和自主神经功能障碍。临床表现是异质性的，个体表现出不同的主要体征，如震颤、痴呆或神经病变。MR成像显示大脑半球和小脑中脚萎缩和片状白色病变。后者已被指定为“MCP标志”，发生在约60%的受影响男性中，并且对FXTAS相对特异。受影响的女性通常疾病不太严重，认知能力下降较少，并且一些症状与男性不同，例如，肌肉疼痛。FXTAS的管理是复杂的，包括评估患者的神经和医疗缺陷，治疗症状，并提供相关的转诊，特别是遗传咨询。治疗是经验性的，基于轶事经验和对FXTAS中也存在的其他疾病症状有效的知识。目前，这种疾病是认识不足，因为第一次发表的报告是在2001年，因为介绍是可变的，主要是由老年人常见的体征组合。然而，准确的诊断对于患者和家庭来说至关重要，因为他们需要了解他们的遗传和健康风险。
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a CGG repeat expansion in the premutation range (55-200) in the fragile X mental retardation 1 gene. Onset is typically in the early seventh decade and men are principally affected. The major signs are cerebellar gait ataxia, intention tremor, frontal executive dysfunction, and global brain atrophy. Other frequent findings are parkinsonism (mild), peripheral neuropathy, psychiatric symptoms (depression, anxiety, agitation), and autonomic dysfunction. The clinical presentation is heterogeneous, with individuals presenting with varied dominating signs, such as tremor, dementia or neuropathy. MR imaging shows atrophy and patchy white matter lesions in the cerebral hemispheres and middle cerebellar peduncles. The latter has been designated the ‘MCP sign’, occurs in about 60% of affected men, and is relatively specific for FXTAS. Affected females generally have less severe disease, less cognitive decline, and some symptoms different from that of men, e.g., muscle pain. Management of FXTAS is complex and includes assessment of the patient's neurological and medical deficits, treatment of symptoms, and provision of relevant referrals, especially genetic counseling. Treatment is empiric, based on anecdotal experience and on knowledge of what works for symptoms of other disorders that also exist in FXTAS. Presently the disorder is under-recognized, since the first published report was in 2001, and since the presentation is variable and mainly consists of a combination of signs common in the elderly. However, accurate diagnosis is critical, for the patient and for the family, as they need education regarding their genetic and health risks.