Orofacial Cleft Characteristics in Van der Woude Syndrome: A Retrospective Study in Japan

Van der Woude syndrome (VWS) is a common syndromic cause of orofacial clefting, yet comprehensive phenotypic data in Asian populations remain limited. This retrospective study delineated the clinical characteristics and anatomical severity of VWS patients managed at Aichi Gakuin University Dental Hospital, Japan (April 1989-September 2026). Among 5528 cleft patients, 22 VWS cases were identified. The cohort demonstrated a female predilection (59.1%) and a high proportion of patients without a documented family history of orofacial clefts or lip pits (59.1%). Pathognomonic lower lip pits were highly prevalent (86.4%) and predominantly bilateral (59.1%). Cleft lip and palate (CLP) was the most frequent phenotype (59.1%), followed by cleft lip and alveolus (22.7%), submucous cleft palate (SMCP) (13.6%), and cleft lip (4.5%). All 19 overt clefts were complete. Notably, Lip-Alveolar-Palate (L-A-P) anatomical mapping revealed eight distinct morphological patterns, with bilateral complete CLP emerging as the most prevalent structural model (22.7%). This study highlights the phenotypic variability and anatomical severity of VWS among Japanese patients treated for orofacial clefts, marked by a skew toward complete CLP and an absence of overt cleft palate. Recognizing this spectrum, including subtle manifestations such as SMCP, is important for accurate diagnosis and genetic counseling, and multicenter studies with genetic testing are needed to define the full range of VWS phenotypes in Asian populations.