Frontotemporal dementia: Genetics and genetic counseling dilemmas
Frontotemporal dementia: Genetics and genetic counseling dilemmas
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DOI：
10.1097/01.nrl.0000138735.48533.26
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发表时间：
2004-09-01
期刊：
影响因子：
1.2
通讯作者：
Grossman, M
中科院分区：
文献类型：
--
作者：
Goldman, JS;Farmer, JM;Grossman, M
背景：额颞叶痴呆（FTD）是一种以人格改变和/或语言障碍为早期症状的神经退行性疾病。大约40%的FTD患者有痴呆家族史;然而，根据我们的经验，只有不到10%的患者具有明确的常染色体显性遗传。据报道，在高达50%的遗传性病例中，微管相关蛋白tau（MAPT）基因突变，但除了有3名以上FTD患者的家族外，这种突变并不常见。FTD的遗传学因临床异质性、可变表达、表型复制、误诊和家族史丢失而变得复杂。本文的目的是使医生认识到遗传模式和遗传问题的FTD家庭和了解遗传咨询strategies.Review Summary：复杂的FTD遗传学和遗传咨询使用4个案例的历史。病例I证明难以获得可靠的FTD家族史。病例2说明了精神科拟症如何使家庭联系研究变得困难。缺乏基因型和表型的相关性和预测性基因检测的FTD家族内的问题是案件3的主题，和案件4显示如何正常老化的语言困难和认知变化可以被误解时，痴呆症的家族史present.Conclusions：医生看到患者可能FTD应该知道的风险的遗传病因。应获得3代家族史，并注意神经、精神和行为症状。在评估可能的遗传病因时，可变表达和表型复制是混杂因素。建议将患者及其家人转介给遗传咨询机构。
Background: Frontotemporal dementia (FTD) is a neurodegenerative disease with early symptoms of personality change and/or language disorder. Approximately 40% of individuals with FTD have a family history of dementia; however, in our experience, less than 10% have clear autosomal dominant inheritance. Mutations in the microtubule-associated protein tau (MAPT) gene have been reported in up to 50% of hereditary cases, but are unusual except in families with more than 3 individuals with FTD. The genetics of FTD is complicated by clinical heterogeneity, variable expression, phenocopies, misdiagnoses, and lost family histories. The objective of this paper is to enable physicians to recognize hereditary patterns and genetic concerns of FTD families and to understand genetic counseling strategies.Review Summary: The complexity of FTD genetics and genetic Counseling are illustrated using 4 case histories. Case I demonstrates the difficulty obtaining a reliable FTD family history. Case 2 illustrates how psychiatric phenocopies can make family linkage studies difficult. The lack of genotype and phenotype correlation and issues of predictive genetic testing within FTD families are the Subject of case 3, and case 4 shows how normal aging language difficulties and cognitive changes can be misinterpreted when a family history of dementia is present.Conclusions: Physicians seeing patients with possible FTD should be aware of the risk of a genetic etiology. A 3-generation family history should be obtained with attention to neurologic, psychiatric, and behavioral symptoms. Variable expression and phenocopies are confounding factors when assessing a possible genetic etiology. Referral of the patient and family for genetic counseling is recommended.