Unit of Neurology V and Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
Unit of Neurodegenerative and Neurometabolic Rare Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
J Alzheimers Dis. 2018;63(1):195-201. doi: 10.3233/JAD-180018.
Frontotemporal dementia (FTD) is clinically characterized by behavioral changes, language impairment, and executive dysfunction. FTD usually belongs to the frontotemporal lobar degeneration (FTLD) disease group, and its familial forms are dominantly inherited and linked to a group of genes relevant to frontal and temporal brain pathology, such as MAPT, GRN, C9ORF72, TARDBP, CHMP2B, VCP, and FUS. However, FTD can also be associated with different clinical or pathological phenotypes caused by mutations in other genes, whose heredity can be dominant or recessive. In this work we report on a familial case of FTD characterized by behavioral changes and aphasia, very early onset and very long duration, choreic movements, and white matter lesions at magnetic resonance imaging. We performed a wide-range genetic analysis, using a next generation sequencing approach, to evaluate a number of genes involved in neurodegeneration. We found a previously unreported compound heterozygous mutation in TREM2, that is commonly associated with the recessively inherited Nasu-Hakola disease. We discuss the differential diagnosis to be taken into account in cases of FTD presenting with atypical features.
额颞叶痴呆（FTD）的临床特征为行为改变、语言障碍和执行功能障碍。FTD 通常属于额颞叶变性（FTLD）疾病组，其家族形式主要为遗传性的，与一组与额叶和颞叶脑病理学相关的基因相关，如 MAPT、GRN、C9ORF72、TARDBP、CHMP2B、VCP 和 FUS。然而，FTD 也可能与其他基因突变引起的不同临床或病理表型有关，其遗传方式可为显性或隐性。在这项工作中，我们报告了一个家族性额颞叶痴呆病例，其特征为行为改变和失语症，发病早且持续时间长，舞蹈样运动和磁共振成像上的白质病变。我们使用下一代测序方法进行了广泛的基因分析，以评估参与神经退行性变的多个基因。我们发现了 TREM2 中一种以前未报道的复合杂合突变，这种突变通常与隐性遗传的 Nasu-Hakola 病有关。我们讨论了在出现非典型特征的 FTD 病例中需要考虑的鉴别诊断。
