背景:在大多数额颞叶变性(FTLD)患者中,退行性过程在45岁至65岁之间开始;年龄小于45岁的发病相对罕见,被认为是非常早发作的FTLD(VEO-FTLD)。
目的:描述临床,遗传,和VEO-FTLD的病理特征。
方法:从成立到2021年9月,在PubMed和Embase进行了系统的文献综述。包括在45岁之前被诊断为明确的FTLD的患者。排除缺乏详细临床数据或遗传和神经病理学数据的患者。表型,基因型,并提取病理数据进行进一步分析。
结果:来自110例VEO-FTLD患者的数据,在累计70种出版物中报告,包括在内。发病年龄为35.09±7.04(14~44)岁。67例患者报告死亡年龄为42.12±7.26(24-58)岁,病程8.13±4.69(1-20)年。行为变异额颞叶痴呆(104/110,94.5%)是最常见的临床亚型,通常表现为去抑制(81.8%)和冷漠(80.9%),常伴有认知障碍(90.9%)和帕金森病(37.3%)。家族性聚集体较高(家族性与散发性,73/37,66.4%);大多数患者携带MAPT基因突变(72.9%家族性,40%零星),其次是C9(18.8%的家族性,10.0%零星),TARDBP(2.1%家族性),和VCP(2.1%家族性)。最常见的神经病理学亚型是tau(43.5%),其次是泛素阳性(24.6%),FUS(20.3%),和TDP43(2.9%)。
结论:VEO-FTLD可能具有独特的临床,遗传,和神经病理学标志物,应在有心理行为症状的年轻患者中考虑。
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).
To delineate the clinical, genetic, and pathological features of VEO-FTLD.
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.
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%).
VEO-FTLD may have unique clinical, genetic, and neuropathological markers and should be considered in young patients with psycho-behavioral symptoms.