背景:脆性X相关震颤/共济失调综合征(FXTAS)和迟发性神经元核内包涵体病(NIID)均显示CGG/GGC三核苷酸重复扩增。由于这些疾病的临床和放射学特征相似,因此很难区分它们。目前尚不清楚皮肤活检可以区分NIID和FXTAS。我们对FXTAS患者进行了皮肤活检,患者有认知功能障碍和无震颤的周围神经病变,最初被怀疑是NIID。
方法:患者接受了神经系统评估和检查,包括实验室测试,电生理测试,成像,皮肤活检,和基因测试。脑MRI在弥散加权成像(DWI)上显示沿皮质髓质交界处的高强度病变,以及小脑中柄征(MCP征)。我们从临床表现和放射学发现怀疑NIID,做了皮肤活检.皮肤活检标本显示泛素和p62阳性的核内包涵体,建议NIID。然而,使用重复引发的聚合酶链反应(RP-PCR)对NIID进行的遗传分析显示,在Notch2N末端样C(NOTCH2NLC)基因中未检测到扩增。然后,我们使用RP-PCR对FXTAS进行了遗传分析,揭示了FMRP翻译调节因子1(FMR1)基因中的CGG/GGC重复扩增。重复的数目是83。我们最终诊断患者为FXTAS而不是NIID。
结论:对于FXTAS和NIID的鉴别诊断,仅靠皮肤活检是不够的;相反,遗传分析,是必不可少的。需要对基于遗传分析的其他病例进行进一步研究,以阐明FXTAS和NIID之间的临床和病理学差异。
BACKGROUND: Both fragile X-associated tremor/ataxia syndrome (
FXTAS) and late-onset neuronal intranuclear inclusion disease (NIID) show CGG/GGC trinucleotide repeat expansions. Differentiating these diseases are difficult because of the similarity in their clinical and radiological features. It is unclear that skin biopsy can distinguish NIID from
FXTAS. We performed a skin biopsy in an
FXTAS case with cognitive dysfunction and peripheral neuropathy without tremor, which was initially suspected to be NIID.
METHODS: The patient underwent neurological assessment and examinations, including laboratory tests, electrophysiologic test, imaging, skin biopsy, and genetic test. A brain MRI showed hyperintensity lesions along the corticomedullary junction on diffusion-weighted imaging (DWI) in addition to middle cerebellar peduncle sign (MCP sign). We suspected NIID from the clinical picture and the radiological findings, and performed a skin biopsy. The skin biopsy specimen showed ubiquitin- and p62-positive intranuclear inclusions, suggesting NIID. However, a genetic analysis for NIID using repeat-primed polymerase chain reaction (RP-PCR) revealed no expansion detected in the Notch 2 N-terminal like C (NOTCH2NLC) gene. We then performed genetic analysis for
FXTAS using RP-PCR, which revealed a repeat CGG/GGC expansion in the FMRP translational regulator 1 (FMR1) gene. The number of repeats was 83. We finally diagnosed the patient with
FXTAS rather than NIID.
CONCLUSIONS: For the differential diagnosis of FXTAS and NIID, a skin biopsy alone is insufficient; instead, genetic analysis, is essential. Further investigations in additional cases based on genetic analysis are needed to elucidate the clinical and pathological differences between FXTAS and NIID.