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Purpose: Cleft lip and/or palate (CLP) is one of the most frequent craniofacial defects that could happen in 1/500 to 1/1000 live birth depending on different racial background. Among different patterns of facial cleft, complete bilateral cleft lip and palate (BCLP) is one of the most challenging cases for orthodontic and surgeons because of their deformed maxillary dental arch and severe skeletal discrepancy. It is also well known that CLP could occur as part of the phenotype in certain congenital diseases. However, from its extremely diversified phenotypic combination, some of the cases that we encounter remains difficult to diagnose. From these reasons, it is important to continuously report the outcome of orthodontic treatment in such cases which exhibit syndromic phenotypes with CLP. Material and Methods: In the present case report, an 18-year-old man with complete bilateral cleft lip and palate, skeletal Class III and open-bite with maxillary constriction, in addition to hypospadias, bubonocele, opisthotonus, and hypertonia was treated with edgewise appliance therapy combined with orthognathic surgery. The treatment began with surgically assisted rapid palatal expansion (SARPE) in anteroposterior and transverse dimensions with a three-way expander to increase the maxillary anteroposterior length and width. After the expansion, the patient underwent Le Fort I osteotomy and bilateral sagittal split osteotomy to correct skeletal Class III and open bite. Results and Conclusion: At the end of the surgical and orthodontic treatments, functional occlusion and an improved facial profile were achieved. We also discuss his diverse general phenotype due to his congenital disease. [ABSTRACT FROM AUTHOR]