Gabriella Miller Kids First Pediatric Research Program in Craniofacial Microsomia

All of the WGS and phenotypic data from this study are accessible through dbGaP and kidsfirstdrc.org, where other Kids First datasets can also be accessed.

Craniofacial microsomia (CFM), also termed hemifacial microsomia or oculo-auricular-vertebral spectrum, is the third most common congenital craniofacial condition. CFM comprises a variable phenotype and the most common features include malformations of the ear (i.e. microtia) and lower jaw (i.e. mandibular hypoplasia) on one or both sides. Microtia in the absence of other anomalies is believed to represent the mildest form of CFM. The cause of CFM is unknown for most affected individuals. We have established a cohort through previous studies and collected DNA to identify the genetic contributions to CFM, which could facilitate diagnosis, tailored treatments and guide prevention strategies. Successful completion of this proposal will advance knowledge in the genetic architecture of susceptibility to CFM and will provide insight about the biological mechanisms underlying craniofacial development. The results from this study have the potential to further research on the etiology of other craniofacial conditions, and the pathogenesis of typical and atypical craniofacial development.
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Probands with isolated microtia or craniofacial microsomia (as defined below) and biological parents were enrolled as part of the FACIAL study, CLOCK study or Project Microtia in the Andean Region.

Participants with at least one of the following criteria were included:
• Microtia
• Mandibular hypoplasia and preauricular tag(s)
• Mandibular hypoplasia and facial tag(s)
• Mandibular hypoplasia and epibulbar dermoid
• Mandibular hypoplasia and lateral oral cleft• Preauricular tag and epibulbar dermoid
• Preauricular tag and lateral oral cleft• Facial tag and epibulbar dermoid
• Lateral oral cleft and epibulbar dermoid

Age: 0-99 years of age
Sporadic or familial cases were included

Exclusion criteria:
• Parent non-English or non-Spanish speaking
• Subjects with a diagnosis of known syndromes with mandibular hypoplasia and/or microtia.
• Abnormal chromosome studies (karyotype or CGH)
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The etiology of CFM is largely unknown; however, the presence of multiple cases within families, reports of individuals with CFM and genomic imbalances, mouse models with CFM malformations and the increased risk of CFM in individuals with specific ethnic backgrounds suggest that genetic variants contribute to CFM
Our goal in this proposal is to identify coding and non-coding variants that are genetic risk factors for CFM by performing whole-genome sequencing (WGS) of case-parent trios with CFM. The cohort was collected through a network of national and international collaborators in projects led by Drs. Luquetti and Heike. Detailed phenotype characterization, family and medical history were collected using the same, standardized data collection tools for the cohort.
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