FXTAS is difficult to differentiate from neuronal intranuclear inclusion disease through skin biopsy: a case report

BMC Neurology

Gen Sobue¹  Hiroyuki Morino²  Hirofumi Maruyama²  Hideshi Kawakami³  Kodai Kume³  Hiroshi Yamashita⁴  Megumi Toko⁴  Tomohiko Ohshita⁴  Takashi Kurashige⁵  Jun Sone⁶  Yasushi Iwasaki⁶ 

[1] Aichi Medical University;Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences;Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University;Department of Neurology, Hiroshima City Asa Citizens Hospital;Department of Neurology, National Hospital Organization Kure Medical Center and Chugoku Caner Center;Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University;

关键词: FXTAS;    NIID;    Skin biopsy;    Genetic analysis;   

DOI  :  10.1186/s12883-021-02425-z

来源: DOAJ

【 摘 要 】

Abstract 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. Case presentation 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.

【 授权许可】

Unknown