CFM involves the asymmetric underdevelopment of facial skeletal bones and soft tissue and occurs in over 1 in 3500 births. Typically affecting the jaw and ear, CFM impairs basic functions such as hearing, speech, respiration, and chewing, in addition to its aesthetic effects. It can be life-threatening due to airway compromise. Multiple complex surgical procedures are often necessary to restore craniofacial form and function. Being male or a multiple birth, having a mother with diabetes, Hispanic ethnicity, and in utero exposure to isotretinoin or thalidomide are the only known risk factors for CFM. A genetic basis for CFM is supported by: case reports with chromosomal anomalies;familial cases suggesting autosomal recessive or dominant inheritance;evidence of genomewide linkage to 14q32 in one pedigree;fourfold familial relative risks;and CFM phenocopies induced through genetic mutations in animals. To our knowledge, there have been no studies of large cohorts of children with CFM in which their phenotypes, treatments, and possible in utero exposures have been systematically characterized. Put simply, there has been very little research about CFM. We propose to address these gaps by recruiting such a cohort of CFM cases as well as parents and unrelated controls for comparison purposes. We are responding to NIH RFA-OD- 09-003, the challenge area 08, Genomics, topic 08-DE-101: """"""""Planning Grants for Genome-wide Studies of Understudied Oral and Craniofacial Diseases and Disorders."""""""" We propose a planning grant that will lead, in two years, to an R01 proposal to fund a multi-center genome-wide association study (GWAS) of CFM to include 500-1000 individuals with CFM.
Our specific aims for the current planning grant are to: 1) recruit 100 children with CFM, along with their parents and unrelated controls, across five study sites, and perform extensive phenotyping of cases;2) develop a data infrastructure to manage all aspects of data collection and participant tracking, training personnel at each site to use this database;3) conduct multi-center reliability studies regarding each data collection component, including CFM case definition and participant questionnaires;4) recruit an additional 10- 25 large craniofacial centers to participate in the GWAS;5) incorporate information from this planning phase to finalize the GWAS study design, select a genotyping platform, and perform sample size estimation. There are approximately 15,000-30,000 children and 35,000-50,000 adults living with CFM in the United States;they and their families could eventually benefit from the results of our research. This work will also elucidate the biology of normal and abnormal jaw and ear development. Our specific goals of developing a rigorous case definition and recruiting a very large number of case participants will jump-start the currently scanty research into this relatively common craniofacial condition. In addition to the planned GWAS, the cohort will enable research into nongenetic etiologies, natural history of CFM, and treatment outcomes. We propose to develop a research collaboration with five craniofacial centers to standardize phenotypic and genetic data collection in 100 children with craniofacial microsomia. The research infrastructure that we develop during this two-year planning grant will lay the foundation required to enable researchers to collect data on a large number of individuals with craniofacial microsomia. It will also enable further research on the etiology and health care outcomes in patients with craniofacial disorders.
We propose to develop a research collaboration with five craniofacial centers to standardize phenotypic and genetic data collection in 100 children with craniofacial microsomia. The research infrastructure that we develop during this two-year planning grant will lay the foundation required to enable researchers to collect data on a large number of individuals with craniofacial microsomia. It will also enable further research on the etiology and health care outcomes in patients with craniofacial disorders.
| Luquetti, Daniela V; Saltzman, Babette S; Vivaldi, Daniela et al. (2012) Evaluation of ICD-9-CM codes for craniofacial microsomia. Birth Defects Res A Clin Mol Teratol 94:990-5 |
| Heike, Carrie L; Stueckle, Laura P; Stuhaug, Erik T et al. (2011) Photographic protocol for image acquisition in craniofacial microsomia. Head Face Med 7:25 |
