Heritability of Oculo-Auriculo-Vertebral Spectrum

我们假设眼-耳-椎谱的最小表达是一种异常程度的面部不对称。眼-耳椎谱（OAVS）是一组复杂多变的疾病，包括Goldenhar综合征和半面小睡眠症，它们都有耳、眼和颈椎异常，通常是单侧表现。人们普遍认为，这些情况至少有一个共同的发育起源，即胚胎第一和第二鳃弓的破坏。该病的单侧表现以及其外表的频繁散发性最初表明其非遗传或环境起源。然而，在相当数量的病例中，积累的证据支持遗传因素。因此，Rollnick和Kaye（1983）在8%的假定未受影响的先证亲属或超过40%的他们所研究的家庭中发现了明显的OAVS特征。Kaye（1992）后来对大量此类家族进行了分离分析，驳斥了非遗传模型。此外，还报道了几例染色体异常，其中存在OAVS的各种成分。最近，一些动物模型的描述也支持OAVS的遗传贡献。我们将研究50个家庭，其中至少有一个成员有临床记录的OAVS。家庭成员将仔细检查病情的最小迹象。此外，我们将进行面部不对称的定量评估，其中异常不对称是统计定义。我们已经开发并测试了两种独特的整体面部不对称测量方法，并在之前收集的1312个正常人的样本中建立了这些测量方法的正常百分位数。对10个OAVS家族的初步研究发现，除先证者外，有5个家庭的面部不对称程度异常。其他家族的收集将使我们能够确定异常的面部不对称是否可以作为识别OAVS家族形式的有效标记，从而导致更有效的分子分析。

We hypothesize that a minimal expression of Oculo-Auriculo-Vertebral Spectrum is a an abnormal degree of facial asymmetry. Oculo-auriculo vertebral spectrum (OAVS) is a complex and variable set of conditions including Goldenhar syndrome and Hemifacial microsomnia that share ear, eye and cervical vertebrae anomalies often expressed unilaterally. It is widely accepted that the conditions share at least a common developmental origin in disruptions of t he embryonic first and second branchial arches. The unilateral presentation of the condition together with the frequent sporadic nature of its appearance originally suggested a non-genetic or environmental origin. However, evidence has accumulated supporting a genetic component in a sizable number of cases. Thus, Rollnick and Kaye (1983) recognized clear features of OAVS in 8% of the supposed unaffected relatives of their probands or in over 40% of the families they studied. Kaye (1992) later performed segregation analysis on a large collec tion of such families and refuted the non-genetic model. In addition, several cases of chromosomal anomalies have been reported in which various components of OAVS were present. Recently, several animal models have been described which also support a genetic contribution to OAVS. We will examine fifty families in which at least one member has clinically documented OAVS. Family members will be give careful examinations for minimal signs of the condition. In addition we will conduct a quantitative assessment of facial asymmetry in which abnormal asymmetry is define statistically. We have developed and tested two unique measures of overall facial asymmetry and established normal percentiles for these measures in a previously collected sample of 1312 normal individuals. Preliminary studies of ten OAVS families have identified five in which individuals other than the proband have abnormal degrees of facial asymmetry. The collection of additional families will allow us to determine if abnorm al facial asymmetry can be an effective marker for identifying familial forms of OAVS thereby leading to more effective molecular analyses.