Heritability of Oculo-Auriculo-Vertebral Spectrum

我们假设，最低限度的表达，眼耳椎光谱是一个异常程度的面部不对称。 眼耳椎谱系（OAVS）是一组复杂多变的疾病，包括Goldenhar综合征和半面微畸形，这些疾病具有耳、眼和颈椎异常，通常表现为单侧。 人们普遍认为，这些疾病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。 单方面的介绍，连同其外观的频繁零星性质的条件最初建议一个非遗传或环境起源。 然而，越来越多的证据表明，在相当数量的病例中存在遗传因素。 因此，Rollnick和Kaye（1983）在8%的先证者未受影响的亲属或超过40%的家庭中发现了明显的OAVS特征。 Kaye（1992）后来对这些家系进行了大量的分离分析，并反驳了非遗传模型。 此外，还报告了几例染色体异常的病例，其中存在OAVS的各种组分。 最近，已经描述了几种动物模型，这些模型也支持对OAVS的遗传贡献。 我们将检查50个家庭，其中至少有一名成员有临床记录的OAVS。家庭成员将接受仔细检查，以寻找最小的病情迹象。 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学定义的。 我们已经开发和测试了两个独特的措施，整体面部不对称性，并建立了正常的标准，这些措施在以前收集的样本1312个正常人。 对10个OAVS家族的初步研究已经确定了5个，其中除先证者外的其他个体具有异常程度的面部不对称。 收集额外的家庭将使我们能够确定是否异常的面部不对称可以是一个有效的标志物，用于识别家族形式的OAVS，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.