Congenital Eyelid Anomalies as Temporal Manifestations Along a Developmental Continuum

PURPOSE: To describe a developmental concept for congenital eyelid anomalies by integrating embryologic evidence and recent molecular data with descriptive anatomy of some of the more common congenital eyelid anomalies. Attention is directed to the importance of developmental stages in which anomalies arise as stage-dependent disturbances along a continuous embryologic timeline, and where minor differences in molecular signaling timing result in graded phenotypic variations. METHODS: Embryologic literature was reviewed and combined with descriptive anatomic, molecular, and genetic studies of eyelid development. Phenotypic variations in congenital eyelid anomalies were evaluated to identify relationships to gestational stages and to identify transitional and overlapping anatomic features. RESULTS: Molecular data show that disruptions in specific genetic regulators and signaling pathways acting at defined eyelid developmental stages can cause phenotypic anomalies. Minor temporal, spatial, and environmental differences in these disruptions result in graded phenotypic expressions within clinically defined anomalies, resulting in transitional and overlapping variants. CONCLUSION: The concept of stage-specific disturbances along the eyelid developmental continuum resulting in graded phenotypic variations helps to clarify the etiology of, and phenotypic relationships among, congenital eyelid abnormalities.