Nevoid Basal Cell Carcinoma Syndrome Associated With Cleft Lip and Palate: A Case Report and Literature Review

Abstract

Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disorder characterized by multisystem anomalies. Although cleft lip and palate (CLP) have been reported in 5% to 8.5% of cases in patients with NBCCS, their pathogenesis and clinical significance remain unclear. The study reports a case of NBCCS with CLP and elucidates its clinical associations and molecular mechanisms through literature reviews. Cases of NBCCS with CLP were searched in PubMed, China National Knowledge Infrastructure (CNKI), and Web of Science databases. Clinical features, genetic data, and phenotypic patterns were retrospectively analyzed. A total of 14 cases were included in this study combined with a 16-year-old female patient we treated, who presented with unilateral CLP and multiple odontogenic keratocysts (OKCs). Among the 15 cases, the male-to-female ratio approaches 1:1. Skeletal anomalies were observed in 86.7% cases, hypertelorism in 53.3%, and nasal deformities in 46.7%. In contrast, classic NBCCS features such as OKCs (53.3%), basal cell carcinomas (BCCs) (20.0%), and palmar/plantar pits (13.3%) were less prevalent compared to classic NBCCS cohorts. All cases met the minor diagnostic criteria for NBCCS, while PTCH1 mutations were detected in 13.3% of patients. This study confirms CLP as an associated symptom of NBCCS and summarizes its molecular mechanisms. The comprehensive analysis of cases suggests that clinicians should consider NBCCS screening in patients with CLP with concomitant skeletal/craniofacial anomalies, even in the absence of typical OKC/BCC phenotypes.