Objective: To determine the incidence and most frequent anatomical locations of residual oronasal fistulas in children with different types of clefts who were treated at the University Department of Maxillofacial and Oral Surgery in Ljubljana. Design: Retrospective analysis of 857 consecutive patients with cleft born between 1984 and 2003. Results: After primary surgical repair, 33 out of 857 (3.9%) children had residual oronasal fistulas. The incidence of clinically significant fistulas that required surgical repair was 17 of 857 (2.0%). In children with unilateral cleft lip and palate (UCLP), bilateral cleft lip and palate (BCLP), or isolated cleft palate (CP), the incidence of palatal fistulas was 23 of 644 (3.6%). Of these palatal fistulas, 12 (1.9%) were clinically significant. Oronasal fistulas were most frequently found in children with BCLP (9 of 88, 10.2%), followed by UCLP (12 of 215, 5.6%) and CP (12 of 341, 3.5%). No fistulas were found in children with unilateral cleft lip and alveolar ridge. In 10 cases (30.3%), the oronasal fistula remained in the alveolar ridge, in 11 cases (33.3%) in the anterior part of the hard palate, and in 11 cases (33.3%) at the junction of the hard and soft palates. In one case (3%), the records were lost. Conclusion: The low incidence of oronasal fistulas is the result of a surgical technique and tensionless suturing, followed by a two-layer closure, two-stage palate repair in BCLP and UCLP patients, and preoperative orthopedics in UCLP cases.

Although the aetiology of non-syndromic orofacial clefts (nsOFCs) is usually multifactorial, syndromic OFCs (syOFCs) are often caused by single mutations in known genes. Some syndromes, e.g., Van der Woude syndrome (VWS1; VWS2) and X-linked cleft palate with or without ankyloglossia (CPX), show only minor clinical signs in addition to OFC and are sometimes difficult to differentiate from nsOFCs. We recruited 34 Slovenian multi-case families with apparent nsOFCs (isolated OFCs or OFCs with minor additional facial signs). First, we examined IRF6, GRHL3, and TBX22 by Sanger or whole exome sequencing to identify VWS and CPX families. Next, we examined 72 additional nsOFC genes in the remaining families. Variant validation and co-segregation analysis were performed for each identified variant using Sanger sequencing, real-time quantitative PCR and microarray-based comparative genomic hybridization. We identified six disease-causing variants (three novel) in IRF6, GRHL3, and TBX22 in 21% of families with apparent nsOFCs, suggesting that our sequencing approach is useful for distinguishing syOFCs from nsOFCs. The novel variants, a frameshift variant in exon 7 of IRF6, a splice-altering variant in GRHL3, and a deletion of the coding exons of TBX22, indicate VWS1, VWS2, and CPX, respectively. We also identified five rare variants in nsOFC genes in families without VWS or CPX, but they could not be conclusively linked to nsOFC.