PURPOSE OF REVIEW - Improved recognition of velocardiofacial syndrome (VCFS) has led to increasing awareness of VCFS by otolaryngologists. Understanding the developmental biologic processes affected in VCFS patients will help improve treatment and outcomes. Advanced application of molecular labeling techniques has better outlined the role of T-Box transcription factor 1 (TBX1) as the primary genetic anomaly leading to VCFS. TBX1 plays multiple roles during branchial, cardiac, and craniofacial development and increased understanding of how these systems are affected by TBX1 mutations will improve patient outcomes. Furthermore, additional modifiers of TBX1 expression have been identified that may explain the variability of VCFS phenotypes. The phenotypic spectrum of VCFS may include cardiac anomalies, velopharyngeal insufficiency, aberrant calcium metabolism, and immune dysfunction. Recent interest has focused on the cognitive and neuropsychiatric manifestations of VCFS. Improved understanding of the biology of VCFS associated mutations has the potential to improve therapeutic outcomes.
RECENT FINDINGS - This article will discuss recent developmental biologic understanding of the role of TBX1 and genetic modifiers generating the phenotypic variability seen in VCFS patients. Special attention is given to advances in the realms of immunodeficiency, hypocalcemia, cardiac and arterial patterning anomalies, velopharyngeal insufficiency, as well as cognitive and psychiatric problems.
SUMMARY - Enhanced understanding of the multiple systems affected by TBX1 mutations will result in improved patient outcomes and improved family education. Future research will lead to improved detection of potential targets for gene therapy and change the way physicians counsel families and treat patients.