Cleft Lip: Aetiology, Genetic Basis and Pathological Anatomy

Abstract

Background: Cleft lip, with or without cleft palate, is a common congenital craniofacial anomaly arising during early embryological development. Its etiology is complex and multifactorial, involving interactions between genetic susceptibility and environmental exposures. Genetic abnormalities may affect essential processes of midfacial development, including cellular patterning, proliferation, extracellular communication, and differentiation, with several genes implicated in syndromic and non-syndromic forms of clefting. Environmental factors, including certain medications, maternal smoking, alcohol exposure, and folate deficiency, may further increase the risk, particularly in genetically susceptible fetuses. The resulting deformity involves complex alterations of the lip, nose, maxillary skeleton, and associated musculature. In unilateral cleft lip, abnormal insertion and discontinuity of the orbicularis oris muscle produce asymmetric forces that contribute to displacement of the columella, nasal septum, and alar base. The clinical presentation varies considerably in severity, ranging from subtle microform defects to complete clefts involving the lip, alveolus, and palate. A comprehensive understanding of the etiological factors, genetic basis, pathological anatomy, and classification of cleft lip is therefore essential for accurate assessment and appropriate surgical planning.