Alzheimer Center, Department of Neurology, Location VU University Medical Center, Amsterdam University Medical Centres, Amsterdam, The Netherlands
Department of Old Age psychiatry, GGZ inGeest Amsterdam locatie De Nieuwe Valerius, Amsterdam, The Netherlands.
J Neurol Neurosurg Psychiatry. 2022 Jan;93(1):93-100. doi: 10.1136/jnnp-2020-325994. Epub 2021 Apr 27.
The chromosome 9 open reading frame 72 gene (C9orf72) hexanucleotide repeat expansion (C9orf72) is the most common genetic cause of behavioural variant frontotemporal dementia (bvFTD). Since the onset of the C9orf72-associated disease is sometimes hard to define, we hypothesise that C9orf72 may cause a lifelong neuropsychiatric vulnerability. The first aim of our study was to explore lifelong behavioural and personality characteristics in C9orf72. Second, we aimed to describe distinctive characteristics of C9orf72 during disease course.
Out of 183 patients from the Amsterdam Dementia Cohort that underwent genetic testing between 2011 and 2018, 20 C9orf72 bvFTD patients and 23 C9orf72 negative bvFTD patients were included. Patients and their relatives were interviewed extensively to chart their biography. Data analysis was performed through a mixed-methods approach including qualitative and quantitative analyses.
Education, type of professional career and number of intimate partners were not different between carriers and non-carriers. Carriers were more often described by their relatives as having 'fixed behavioural patterns in daily life' and with limited empathy already years before onset of bvFTD symptoms. In carriers, disease course was more often characterised by excessive buying and obsessive physical exercise than in non-carriers.
This is the first study thoroughly exploring biographies of bvFTD patients with C9orf72, revealing that subtle personality traits may be present early in life. Our study suggests that C9orf72 exerts a lifelong neuropsychiatric vulnerability. This may strengthen hypotheses of links between neurodevelopmental and neurodegenerative diseases. Moreover, the presence of a distinct C9orf72 -associated syndrome within the FTD spectrum opens doors for investigation of vulnerable neuronal networks.
染色体 9 开放阅读框 72 基因（C9orf72）六核苷酸重复扩展（C9orf72）是行为变异额颞叶痴呆（bvFTD）最常见的遗传原因。由于 C9orf72 相关疾病的发病有时难以定义，我们假设 C9orf72 可能导致终生神经精神易感性。我们研究的首要目的是探索 C9orf72 患者的终生行为和人格特征。其次，我们旨在描述 C9orf72 在疾病过程中的独特特征。
在 2011 年至 2018 年间接受基因检测的 183 名阿姆斯特丹痴呆队列患者中，纳入了 20 名 C9orf72 bvFTD 患者和 23 名 C9orf72 阴性 bvFTD 患者。对患者及其亲属进行了广泛的访谈，以绘制他们的传记。数据分析采用混合方法，包括定性和定量分析。
携带者和非携带者的教育程度、职业类型和亲密伴侣数量没有差异。亲属更常描述携带者在日常生活中有“固定的行为模式”，并且在 bvFTD 症状出现前多年就已经缺乏同理心。在携带者中，疾病过程更常表现为过度购物和过度体育锻炼，而非携带者则较少出现这种情况。
这是第一项彻底探索 C9orf72 bvFTD 患者传记的研究，揭示了微妙的人格特征可能早在生命早期就存在。我们的研究表明，C9orf72 对神经精神产生终生易感性。这可能加强了神经发育和神经退行性疾病之间存在联系的假说。此外，在 FTD 谱系中存在独特的 C9orf72 相关综合征，为研究脆弱的神经元网络打开了大门。
