scholarly journals Prevalence of Fragile X-Associated Tremor/Ataxia Syndrome in Patients with Cerebellar Ataxia in Japan

2021 ◽  
Author(s):  
Yujiro Higuchi ◽  
Masahiro Ando ◽  
Akiko Yoshimura ◽  
Satoshi Hakotani ◽  
Yuki Koba ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Cerebellar Ataxia ◽  
Fragile X ◽  
Genetic Diagnosis ◽  
Japanese Patients ◽  
High Signal ◽  
Intranuclear Inclusion ◽  
Neuronal Intranuclear Inclusion ◽  
Male Patients ◽  
Ataxia Syndrome

AbstractThe presence of fragile X mental retardation 1 (FMR1) premutation has been linked to patients with a certain type of cerebellar ataxia, the fragile X-associated tremor/ataxia syndrome (FXTAS). However, its prevalence in Japan has yet to be clarified. The aim of the present study is to determine the prevalence of FXTAS in Japanese patients with cerebellar ataxia and to describe their clinical characteristics. DNA samples were collected from 1328 Japanese patients with cerebellar ataxia, referred for genetic diagnosis. Among them, 995 patients with negative results for the most common spinocerebellar ataxia subtypes were screened for FMR1 premutation. Comprehensive clinical and radiological analyses were performed for the patients harbouring FMR1 premutation. We herein identified FMR1 premutation from one female and two male patients, who satisfied both clinical and radiological criteria of FXTAS (0.3%; 3/995) as well. Both male patients presented with high signal intensity of corticomedullary junction on diffusion-weighted magnetic resonance imaging, a finding comparable to that of neuronal intranuclear inclusion disease. The female patient mimicked multiple system atrophy in the early stages of her disease and developed aseptic meningitis with a suspected immune-mediated mechanism after the onset of FXTAS, which made her unique. Despite the lower prevalence rate in Japan than the previous reports in other countries, the present study emphasises the necessity to consider FXTAS with undiagnosed ataxia, regardless of men or women, particularly for those cases presenting with similar clinical and radiological findings with multiple system atrophy or neuronal intranuclear inclusion disease.

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

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Megumi Toko ◽  
Tomohiko Ohshita ◽  
Takashi Kurashige ◽  
Hiroyuki Morino ◽  
Kodai Kume ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Skin Biopsy ◽  
Trinucleotide Repeat ◽  
Late Onset ◽  
Fragile X ◽  
Brain Mri ◽  
Intranuclear Inclusion ◽  
Neuronal Intranuclear Inclusion ◽  
Cerebellar Peduncle ◽  
Ataxia Syndrome

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.

scholarly journals NOTCH2NLC-linked neuronal intranuclear inclusion body disease and fragile X-associated tremor/ataxia syndrome

Brain ◽  
2020 ◽  
Vol 143 (8) ◽  
pp. e69-e69
Author(s):  
Adeline S L Ng ◽  
Zheyu Xu ◽  
Zhiyong Chen ◽  
Yi Jayne Tan ◽  
Weng Khong Lim ◽  
...  
Keyword(s):  
Inclusion Body ◽  
Fragile X ◽  
Intranuclear Inclusion ◽  
Neuronal Intranuclear Inclusion ◽  
Inclusion Body Disease ◽  
Ataxia Syndrome

scholarly journals Genetic and Pathological Characteristic Patterns of a Family With Neuronal Intranuclear Inclusion Disease

2020 ◽  
Vol 79 (12) ◽  
pp. 1293-1302
Author(s):  
Shugang Zhang ◽  
Qixing Gong ◽  
Di Wu ◽  
Yun Tian ◽  
Lu Shen ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Fragile X ◽  
Cerebrovascular Diseases ◽  
Pathological Examination ◽  
Positive Staining ◽  
Intranuclear Inclusion ◽  
Cgg Repeats ◽  
Genetic Features ◽  
Neuronal Intranuclear Inclusion ◽  
Ataxia Syndrome

Abstract Neuronal intranuclear inclusion disease (NIID) is a rare, progressive neurodegenerative disorder. This study aimed to investigate clinical, imaging, genetic, and dermatopathological characteristics of a family with adult-onset NIID. The proband was a 62-year-old woman with 3 brothers and 2 sisters. Of these, 4 had symptoms of paroxysmal visual field defect, extrapyramidal symptoms, dysautonomia, emotional changes, and cognitive dysfunction. Genetic examination revealed no abnormality related to cerebrovascular diseases. More than 200 CGG repeats of FMR1 gene cause fragile X-associated tremor/ataxia syndrome (FXTAS) whereas repeats of the proband were found 29 times, which excluded FXTAS. Quantitative reverse transcription polymerase chain reaction (PCR) and GC-rich-PCR identified an expanded GGC repeat (with ∼100 repeats) in the 5′ region of NOTCH2NLC in the patient and her 2 younger brothers. Pathological examination found eosinophilic intranuclear inclusions inside adipocytes, fibrocytes, and sweat gland cells. Immunohistochemistry and immunofluorescence staining revealed positive staining for ubiquitin and p62. The detailed pathological and genetic features of this NIID family provide a valuable contribution to the existing knowledge base of this rare disorder.

scholarly journals FMR1 Premutations Associated With Fragile X–Associated Tremor/Ataxia Syndrome in Multiple System Atrophy

2005 ◽  
Vol 62 (6) ◽  
Author(s):  
Valérie Biancalana ◽  
Mathias Toft ◽  
Isabelle Le Ber ◽  
François Tison ◽  
Elisabeth Scherrer ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Fragile X ◽  
Ataxia Syndrome

scholarly journals Adult-onset neuronal intranuclear inclusion disease, with both stroke-like onset and encephalitic attacks: a case report

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Huang ◽  
Ge Jin ◽  
Qun-ling Zhan ◽  
Yun Tian ◽  
Lu Shen
Keyword(s):  
Case Report ◽  
Clinical Characteristics ◽  
Spherical Inclusion ◽  
Clinical Manifestations ◽  
Brain Magnetic Resonance Imaging ◽  
High Signal ◽  
Autonomic Nerves ◽  
Intranuclear Inclusion ◽  
Main Site ◽  
Neuronal Intranuclear Inclusion

Abstract Background Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease, the clinical manifestations of which are complex and easily misdiagnosed. NIID clinical characteristics are varied, affecting the central and peripheral nervous systems and autonomic nerves. In this study, we present an NIID case with both stroke-like onset and encephalitic attacks, which is a rare case report. Case presentation A 68-year-old Chinese female presented with sudden aphasia and limb hemiplegia as the first symptoms, as well as fever, cognitive impairment and mental irritability from encephalitic attacks. During hospitalization, a brain magnetic resonance imaging (MRI) examination detected high signal intensity from diffusion-weighted imaging (DWI) of the bilateral frontal grey matter-white matter junction. Electrophysiological tests revealed the main site of injury was at the myelin sheath in the motor nerves. A skin biopsy revealed eosinophilic spherical inclusion bodies in the nuclei of small sweat gland cells, fibroblasts and fat cells, whilst immunohistochemistry revealed that p62 and ubiquitin antibodies were positive. From genetic analyses, the patient was not a carrier of the fragile X mental retardation 1 (FMR1) permutation, but repeated GGC sequences in the NOTCH2NLC gene confirmed an NIID diagnosis. Through antipsychotic and nutritional support therapy, the patient’s symptoms were completely relieved within 3 weeks. Conclusions This report of an NIID case with both stroke-like onset and encephalitic attacks provides new information for NIID diagnoses, and a comprehensive classification of clinical characteristics.

scholarly journals The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA Study Group

Brain ◽  
2005 ◽  
Vol 128 (8) ◽  
pp. 1855-1860 ◽  
Author(s):  
C. Kamm ◽  
D. G. Healy ◽  
N. P. Quinn ◽  
U. Wüllner ◽  
J. C. Moller ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Multiple System Atrophy ◽  
Fragile X ◽  
Study Group ◽  
Ataxia Syndrome
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