GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Parkinsonism Relat Disord. 2013 Mar;19(3):359-62. doi: 10.1016/j.parkreldis.2012.09.015. Epub 2012 Oct 23.
Essential tremor (ET) is considered to be a highly heritable disorder, yet no susceptibility genes have been identified. The search for ET genes is severely hampered by clinical and genetic heterogeneity; the existence of this heterogeneity complicates the genetic analyses. We sought to determine the prevalence and clinical features of unreported dystonia in a family study of "pure" ET.
ET probands and their reportedly affected first-and second-degree relatives were enrolled in a genetics study, the Family Study of Essential Tremor (FASET) at Columbia University Medical Center. The goal was to enroll cases with "pure" ET (i.e., ET without dystonia or other neurological problems). Each enrollee underwent a detailed neurological evaluation.
There were 100 enrollees (28 probands, 72 relatives). Dystonia (primarily torticollis) occurred in 9 (32.1%) of 28 families, with 5 cases in one family, 2 cases in two families, and 1 case in six families. Those affected with dystonia included 3 (10.7%) probands and 12 (16.7%) relatives. There was a gender predilection: 14/15 (93.3%) with dystonia vs. 41/85 (48.2%) without dystonia were women (p = 0.001). Dystonia was previously undiagnosed in 14/15 (93.3%) cases.
Dystonia (esp. torticollis in women) was present in nearly one-third of the ET families in a genetics study, including 10.7% of ET probands. Dystonia was unreported and previously undiagnosed in nearly all of these individuals. The overarching biological issue is whether ET and dystonia should be regarded as one disease or two; this has obvious implications for the structuring of analyses in genetic studies.
特发性震颤（ET）被认为是一种高度遗传性疾病，但尚未发现易感基因。ET 基因的研究受到临床和遗传异质性的严重阻碍；这种异质性的存在使遗传分析变得复杂。我们试图在哥伦比亚大学医学中心的特发性震颤家族研究（FASET）中确定“纯”ET 家族中未报告的肌张力障碍的患病率和临床特征。
ET 先证者及其据报道受影响的一级和二级亲属参加了一项遗传学研究，即哥伦比亚大学医学中心的特发性震颤家族研究（FASET）。目的是招募“纯”ET（即无肌张力障碍或其他神经系统问题的 ET）病例。每位入组者均接受详细的神经学评估。
共有 100 名入组者（28 名先证者，72 名亲属）。肌张力障碍（主要为斜颈）发生在 28 个家庭中的 9 个（32.1%），其中 1 个家庭中有 5 例，2 个家庭中有 2 例，6 个家庭中有 1 例。受影响的肌张力障碍包括 3 名（10.7%）先证者和 12 名（16.7%）亲属。存在性别倾向：15 例（93.3%）有肌张力障碍的患者 vs. 85 例（48.2%）无肌张力障碍的患者均为女性（p=0.001）。14/15（93.3%）例肌张力障碍患者此前未被诊断。
在一项遗传学研究中，近三分之一的 ET 家族存在肌张力障碍（尤其是女性的斜颈），包括 10.7%的 ET 先证者。这些患者几乎都未报告且此前未被诊断出肌张力障碍。首要的生物学问题是特发性震颤和肌张力障碍是否应被视为一种疾病或两种疾病；这对遗传研究中分析的构建具有明显的影响。
