This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Blepharo-Cheilo-Dontic Syndrome (BCDS) is a rare, autosomal dominant syndrome with a set of seemingly unrelated phenotypic features in multiple organ systems. There are three cardinal features: ectropion of the eyelids, bilateral cleft lip and palate, and missing or conical teeth. An additional set of variably penetrant features involving ectodermal/endodermal inductions have also been reported. While there are fewer than a dozen reports of the syndrome in almost one hundred years, the high proportion of patients with bilateral cleft lip and palate make this a particularly important syndrome to study. This is a rare and severe disorder that has resisted traditional mapping efforts. The purpose of the study is two-fold. First, detailed medical and dental re-examinations will be performed on a cohort of cases previously treated at Children's Hospital Boston, displaying cardinal features of BCDS, in order to better describe this syndrome. Second, we are searching for causative mutations using a variety of methods in the hope of understanding the genetic theme that unites these different pathologies. A set of candidate genes identified from comparison of BCDS to similar syndromes in humans and to developmental processes found in specific mouse knockouts, will be sequenced. Comparative Genome Hybridization (CGH) protocols will be used to look for aneuploides that might identify the locus of a pathological translocation. Fluorescence In Situ Hybridization (FISH) will be used to look for smaller deletions at candidate gene loci. Thyroid function will be examined, as recent reports suggest hypothyroidism or even thyroid agenesis in some patients. Chart review of nine patients suggests several new phenotypes that are found in different families. The candidate gene sequencing (CGH) and FISH protocols, and the thyroid function tests, are ongoing as patients are enrolled in the study. We hope to better describe the Blepharo-Cheilo-Dontic Syndrome and find its causative mutations in the near future.
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