Exome Sequencing Studies in Syndromic Patients With Cleft Lip and/or Palate: Systematic Review

Objective: The etiology of syndromic cleft lip and/or cleft palate (CL/P) is multifactorial and polygenic. This study aims to identify genetic variants diagnosed by exome sequencing and present in this type of patients. Design: Systematic review. Methods: A systematic review was performed according to the PRISMA guidelines in the PubMed database including the terms “cleft palate,” “cleft lip,” “cleft lip and palate,” “syndromic,” “sequencing,” and “exome.” Patients and participants: Patients with syndromic CL/P were included. Main outcome measures: Genetic variants present in patients diagnosed by exome sequencing. Results: A total of 19 articles were included, of which a total of 62 variants were identified in 41 patients. Patients were mainly from Brazil (38.7%, 24/62), the United States (11.3%, 7/62), China (11.3%, 7/62), the United Kingdom (9.7%, 6/62), and Asia (6.5%, 4/62). Regarding variants, 54 variants were identified only once and 4 variants were found twice in different patients. The genes most affected by the variants are: CHD7 (4.8%, 3/62), TP63 (4.8%, 3/62), MEIS2 (6.5%, 4/62), and SATB2 (6.5%, 4/62). Conclusion: Syndromic CL/P presents a great phenotypic variability, which makes it difficult to associate it with a single genetic cause or known syndrome. Although variants have been identified in some key genes, their impact on embryonic development is still not fully understood. The implementation of advanced genomic sequencing techniques is key to improving diagnosis and clinical care of patients.