Van der woude syndrome with associated scaphocephaly: a rare case report

The purpose of this case is to provide a descriptive report of a rare combination of Van der Woude syndrome, recurrent in three generations of the same family, in a female patient with bilateral cleft lip and palate associated with a sagittal craniosynostosis (scaphocephaly).

Rare and Multiple Hypodontia in Van der Woude Syndrome: Case Report

Van der Woude syndrome (VWS) is a rare syndrome of genetic etiology, commonly occasioned by mutations in the IRF6 gene and that causes disorders in craniofacial development. VWS is characterized by the presence of paramedian fistulas in the lower lip and cleft lip and / or cleft palate. Although some dental phenotypes have been reported in this syndrome, multiple and rare hypodontias were not described. Through this case report, we present a case of Van der Woude Syndrome (VWS) with rare and multiple hypodontia in which clinical data and radiographic exams were evaluated. The patient presented hypodontia of eight permanent teeth (lateral incisors, second premolars and second molars). So, when the dentist recognizes multiple and/or rare hypodontias, for an accurate diagnosis, detailed examination of the lower lip is indicated, as well as a survey of the family history and referral for genetic counseling, since the syndrome presents high penetrance. The patient is expected to be rehabilitated to have a good quality of life. Rehabilitation in these cases requires alveolar bone graft, orthodontics and prosthesis to replace missing teeth.

“VAN DER WOUDE SYNDROME: REPORT OF TWO CASES”

Van Der Woude syndrome is a rare autosomal dominant condition which is associated with developmental malformations involving lips, palate. This syndrome can be a genetic origin due to Microdeletion of chromosome bands 1q32-q41 and also mutation of Interferon regulatory factor 6 (IRF-6) can be a pathogenic cause. We report two interesting cases of Van Der Woude syndrome with lip pits and orofacial features.

A Novel IRF6 Frameshift Mutation in a Large Chinese Pedigree With Van der Woude syndrome

Aims: Van der Woude syndrome (VWS) is one of the most common craniofacial anomalies, causing significant functional and psychological burden to the patients. This study aimed to identify the genetic cause of VWS in a Chinese family. Methods: Whole genome sequencing (WGS) was performed to screen for pathogenic mutations. Various Bioinformatics tools were used to assess the pathogenicity of the variants. Cosegregation analysis of the candidate variant was carried out. Interpretation of variants was performed according to the American College of Medical Genetics and Genomics guidelines. Results: A novel frameshift duplication c.373_374dupAA (p.Asn125Lys fs*43) was identified in exon 4 of the interferon regulatory factor 6 (IRF6) gene in all 3 affected members, which were not found in unaffected family members. The novel mutation leads to a frameshift and a premature stop codon which caused putative truncated protein. Protein alignment indicated high evolutionary conservation of the p.N125 residue, and this mutation was predicted by online tools to be damaging and deleterious. Conclusions: This study demonstrates that the novel mutation c.373_374dupAA (p.Asn125Lysfs*43) in the IRF6 gene corresponds to the VWS in this family. The discovery of this pathogenic variant enriches the genotypic spectrum of IRF6 gene and contributes to genetic diagnosis and counseling of families with VWS.