Ectodermal dysplasias, a diverse group of disorders affecting ectodermal structures, represent challenges in diagnosis and management due to their varied clinical presentations.This article presents an exceptional case of Cleft Lip and Palate-Ectrodactyly and Ectodermal Dysplasia syndrome, highlighting a previously unreported chromosomal alteration (deletion on chromosome 21) in the absence of hereditary genetic backgrounds up to the third generation.The main syndrome, EEC, manifests with characteristic features such as ectrodactyly, cleft lip, and varied ectodermal anomalies.Genetic counseling addressed autosomal dominant inheritance, incomplete penetrance, and variable expression, emphasizing the importance of multidisciplinary follow-up for tailored medical care.A systematic literature review and comparison with the presented case underscored the significance of timely diagnosis and the necessity of genetic studies to inform parents about potential risks.The confirmed deletion on chromosome 21 adds a unique dimension to the case, reinforcing the need for a comprehensive approach involving a multidisciplinary healthcare team for optimal patient outcomes.