Clinical, Genetic, and Pathological Features of very Early Onset Frontotemporal Lobe Degeneration: A Systematic Review.

IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY
Min Chu, Liyong Wu, Li Liu, Haitian Nan, Deming Jiang, Yihao Wang, Pedro Rosa-Neto
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引用次数: 1

Abstract

Background: In most patients with frontotemporal lobe degeneration (FTLD), the degenerative process begins between the ages 45 and 65 years; onset younger than 45 years is relatively rare and considered very early onset FTLD (VEO-FTLD).

Objective: To delineate the clinical, genetic, and pathological features of VEO-FTLD.

Methods: A systematic literature review was carried out in PubMed and Embase from inception to September 2021. Patients diagnosed with definite FTLD with onset before age 45 years were included. Patients lacking detailed clinical data or both genetic and neuropathological data were excluded. Phenotypic, genotypic, and pathological data were extracted for further analyses.

Results: Data from 110 patients with VEO-FTLD, reported in a cumulative 70 publications, were included. Age of onset was 35.09 ± 7.04 (14-44) years. Sixty-seven patients were reported age at death of 42.12 ± 7.26 (24-58) years, with a disease course lasting 8.13 ± 4.69 (1-20) years. Behavioural variant frontotemporal dementia (104/110, 94.5%) was the most common clinical subtype, often manifesting as disinhibition (81.8%) and apathy (80.9%), and frequently accompanied by a cognitive deficit (90.9%) and parkinsonism (37.3%). Frequency of familial aggregation was high (familial vs. sporadic, 73/37, 66.4%); most patients carried MAPT gene mutations (72.9% in familial, 40% in sporadic), followed by C9 (18.8% in familial, 10% in sporadic), TARDBP (2.1% in familial), and VCP (2.1% in familial). The most common neuropathology subtype was tau (43.5%), followed by ubiquitin- positive (24.6%), FUS (20.3%), and TDP 43 (2.9%).

Conclusion: VEO-FTLD may have unique clinical, genetic, and neuropathological markers and should be considered in young patients with psycho-behavioral symptoms.

早发额颞叶变性的临床、遗传和病理特征:一项系统综述。
背景:在大多数额颞叶变性(FTLD)患者中,退行性过程开始于45至65岁之间;发病年龄小于45岁的FTLD相对罕见,被认为是非常早发的FTLD (VEO-FTLD)。目的:探讨VEO-FTLD的临床、遗传和病理特点。方法:系统回顾PubMed和Embase自成立至2021年9月的文献。确诊的FTLD患者在45岁前发病。缺乏详细临床资料或遗传和神经病理资料的患者被排除在外。提取表型、基因型和病理数据作进一步分析。结果:纳入了110例VEO-FTLD患者的数据,这些数据已在70篇出版物中报道。发病年龄为35.09±7.04(14-44)岁。67例患者报告死亡年龄42.12±7.26(24-58)岁,病程8.13±4.69(1-20)年。行为变异性额颞叶痴呆(104/110,94.5%)是最常见的临床亚型,常表现为去抑制(81.8%)和冷漠(80.9%),常伴有认知缺陷(90.9%)和帕金森病(37.3%)。家族性聚集率高(家族性vs散发性,73/37,66.4%);大多数患者携带MAPT基因突变(家族性72.9%,散发性40%),其次是C9(家族性18.8%,散发性10%)、TARDBP(家族性2.1%)和VCP(家族性2.1%)。最常见的神经病理亚型为tau(43.5%),其次是泛素阳性(24.6%)、FUS(20.3%)和TDP 43(2.9%)。结论:VEO-FTLD可能具有独特的临床、遗传和神经病理学标志,在有心理行为症状的年轻患者中应予以考虑。
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来源期刊
Current Alzheimer research
Current Alzheimer research 医学-神经科学
CiteScore
4.00
自引率
4.80%
发文量
64
审稿时长
4-8 weeks
期刊介绍: Current Alzheimer Research publishes peer-reviewed frontier review, research, drug clinical trial studies and letter articles on all areas of Alzheimer’s disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer’s disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer’s disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer''s disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer’s disease. Current Alzheimer Research provides a comprehensive ''bird''s-eye view'' of the current state of Alzheimer''s research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.
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