Inheritance of frontotemporal dementia
Inheritance of frontotemporal dementia
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DOI：
10.1001/archneur.56.7.817
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发表时间：
1999-07-01
影响因子：
--
通讯作者：
Geschwind, DH
中科院分区：
文献类型：
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作者：
Chow, TW;Miller, BL;Geschwind, DH
背景资料：以往的额颞叶痴呆（FTD）家族研究支持常染色体显性遗传模式，但大多数研究都描述了个别家族中的遗传传递，特别是在多个受累个体的存在下。目的：在一大组FTD指数病例中调查FTD和相关疾病的家族表现和遗传，以确定痴呆家族史。设计和设置：我们在一所大学医院和一所大学附属医院采访了家庭成员，并审查了医疗记录和尸检报告，以确定家族性FTD的频率和最可能的遗传方式。特征性的家庭与疾病的描述，沿着的历史，临床表现，和神经影像学结果在这些family.Patients和参与者的成员：42指数例FTD的平均发病年龄为56.1岁（范围，40-69岁）。在这些患者中，21例（50%）为女性。除一名患者外，所有患者均为白色。参与者包括男性和女性的配偶和子女的索引cases.Results：42例FTD的情况下，19（45%）有至少1个其他家庭成员与FTD的频谱障碍，被认为是家族性病例。大多数（17例[89%]）家族性FTD病例显示与显性遗传一致的模式。如果排除抑郁症，家族性病例从19例（45%）减少到17例（40%），其中15例（88%）显示出显性传播模式。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的人格和行为改变（19 [43%]），其次是精神疾病（14 [33%]），无行为改变的痴呆（5 [11%]），肌萎缩侧索硬化（5 [11%]）和帕金森综合征（2 [5%]）。两个受影响的非索引病例有双重表现的诊断。平均发病年龄为56.1岁，在家族性和非家族性病例之间没有显著差异。FTD相关症状的发作发生在65岁后，只有4（10%）的42个指数的情况下，3（5%）的60受影响的relations.Conclusions：家族性FTD通常是遗传的常染色体显性遗传模式。最初的发病是潜伏的，通常包括早老期发生的情绪和行为变化，这些变化通常被错误地归因于其他非神经学原因。虽然FTD在北美的确切发病率尚不清楚，但它是最常见的早老性痴呆之一。
Background: Previous studies of families with frontotemporal 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.Objective: 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.Design and Setting: 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.Patients and Participants: 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.Results: Of 42 FTD cases, 19 (45%) had at least 1 other 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.Conclusions: 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.