Chow T W, Miller B L, Hayashi V N, Geschwind D H
Department of Neurology, Reed Neurological Research Center, University of California, Los Angeles, School of Medicine, 90095-1769, USA.
Arch Neurol. 1999 Jul;56(7):817-22. doi: 10.1001/archneur.56.7.817.
Previous studies of families with fronto-temporal dementia (FTD) support an autosomal dominant inheritance pattern, but most studies have described genetic transmission in individual families specifically selected for the presence of multiple affected individuals.
To investigate the familial presentation and inheritance of FTD and related disorders among a large group of FTD index cases unselected for family history of dementia.
We interviewed family members and reviewed medical records and autopsy reports at a university hospital and a university-affiliated hospital to determine the frequency of familial FTD and the most likely mode of inheritance. Characteristic families with the disorder are described, along with the history, clinical findings, and neuroimaging results in affected members of these families.
The 42 index cases of FTD had a mean age of onset of 56.1 years (range, 40-69 years). Of these patients, 21 (50%) were women. All but one of the patients were white. Participants included male and female spouses and children of the index cases. family member with an FTD spectrum disorder and were considered familial cases. The majority (17 [89%]) of familial FTD cases showed a pattern consistent with dominant inheritance. If depression is excluded, familial cases decrease from 19 (45%) to 17 (40%), of which 15 (88%) showed a dominant transmission pattern. The initial presentations in the nonindex familial cases varied but most frequently consisted of personality and behavioral changes that preceded cognitive impairment (19 [43%]), followed by psychiatric illness (14 [33%]), dementia without behavioral change (5 [11%]), amyotrophic lateral sclerosis (5 [11%]), and parkinsonism (2[5%]). Two of the affected nonindex cases had dual presenting diagnoses. The average age of onset was 56.1 years and did not differ significantly between familial and nonfamilial cases. Onset of FTD-related symptoms occurred after the age of 65 years in only 4(10%) of 42 index cases and 3 (5%) of 60 affected relatives.
Familial FTD is usually inherited in an autosomal dominant pattern. The initial onset is insidious, often consisting of mood and behavioral changes occurring in presenile years that are often erroneously attributed to other nonneurologic causes. Although the precise incidence of FTD in North America is not known, it is one of the most common presenile dementias.
既往对额颞叶痴呆（FTD）患者家系的研究支持常染色体显性遗传模式，但大多数研究描述的是特意挑选出的有多个受累个体的单个家系中的基因传递情况。
在一大群未因痴呆家族史而被挑选的FTD索引病例中，调查FTD及相关疾病的家族表现和遗传情况。
我们在一家大学医院和一家大学附属医院对家庭成员进行了访谈，并查阅了病历和尸检报告，以确定家族性FTD的发生率以及最可能的遗传模式。描述了患有该疾病的典型家系，以及这些家系中受累成员的病史、临床发现和神经影像学结果。
42例FTD索引病例的平均发病年龄为56.1岁（范围40 - 69岁）。这些患者中，21例（50%）为女性。除1例患者外，其他患者均为白人。参与者包括索引病例的配偶及子女。有FTD谱系障碍的家庭成员被视为家族性病例。大多数（17例[89%]）家族性FTD病例呈现出符合显性遗传的模式。若排除抑郁症，家族性病例从19例（45%）降至17例（40%），其中15例（88%）呈现显性遗传模式。非索引家族性病例的初始表现各不相同，但最常见的是认知障碍之前出现的人格和行为改变（19例[43%]），其次是精神疾病（14例[33%]）、无行为改变的痴呆（5例[11%]）、肌萎缩侧索硬化（5例[11%]）和帕金森综合征（2例[5%]）。2例受累的非索引病例有双重诊断。平均发病年龄为56.1岁，家族性和非家族性病例之间无显著差异。在42例索引病例中，仅4例（10%）以及60例受累亲属中仅3例（5%）在65岁以后出现FTD相关症状。
家族性FTD通常以常染色体显性模式遗传。初始发病隐匿，常表现为老年前期出现的情绪和行为改变，常被错误地归因于其他非神经学原因。尽管北美FTD的确切发病率尚不清楚，但它是最常见的老年前期痴呆之一。
