Heritability of Oculo-Auriculo-Vertebral Spectrum


Principal Investigator: Richard E Ward
Abstract: 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.
Funding Period: 2001-04-01 - 2004-02-28
more information: NIH RePORT