SA3 - Cleft Palate Outcomes in Patients With 22q11-Related Genetic Syndromes: A Matched Cohort Study From Two Decades of Practice

Abstract: Background: Cleft palate in patients with 22q11-related genetic syndromes, including 22q11.2 deletion/duplication syndromes and related phenotypes, presents unique perioperative and longitudinal management challenges. Although speech and velopharyngeal outcomes are known to differ in this population, comparative surgical outcome data relative to nonsyndromic peers remain limited. This study compared cleft palate timing and outcomes between patients with 22q11-related syndromes and a matched nonsyndromic cohort.

Methods: A retrospective matched-cohort study was performed at a tertiary children's hospital from 2005 to 2025. Patients with 22q11-related genetic syndromes and cleft phenotypes involving the palate (including cleft lip and palate, isolated cleft palate, and submucosal cleft palate) were matched in a 1:3 fashion without replacement to nonsyndromic controls using cleft phenotype, sex, Veau class, cleft palate laterality, and age proximity. Cleft palate outcomes assessed included age at palatoplasty, readmission, velopharyngeal insufficiency (VPI) surgery, orthognathic surgery, and neighborhood-level deprivation using the State-Specific Percentile of Area Deprivation Index (ADI) score from zip code. Intraoperative and postoperative cleft palate complications were analyzed as derived binary outcomes, with any nonblank free-text entry other than "None" counted as a complication. Among patients with cleft lip and palate, cleft lip intraoperative and postoperative complications were analyzed similarly. Continuous variables were compared with nonparametric testing and categorical variables with chi-square or Fisher's exact tests.

Results: Thirty-six patients with 22q11-related syndromes were matched to up to 100 nonsyndromic controls, depending on outcome-specific data availability. Patients with 22q11-related syndromes underwent palatoplasty at an older age than controls (median 2.4 years [IQR 1.43-7.48] vs 1.23 years [IQR 0.923-4.93], P = .021). Rates of readmission after cleft palate repair did not differ, with no readmissions observed in either cohort among patients with available data (0/33 vs 0/12, P = 1.00). However, patients with 22q11-related syndromes more frequently required secondary VPI surgery (30.6% vs 11.0%, RR 2.78, OR 3.56, P = .007). Orthognathic surgery rates were not significantly different between groups (5.6% vs 2.5%, P = .59). Cleft palate intraoperative complications were more common in the 22q11 cohort (8.3% vs 0%, P = .017), as were postoperative cleft palate complications (11.1% vs 0%, P = .004). In the cleft lip and palate subgroup, cleft lip intraoperative and postoperative complication rates were not significantly different. Neighborhood deprivation did not differ between cohorts based on state-specific ADI percentile (median 5.7 [IQR 4.56-7.04] vs 5.21 [IQR 4.33-7.83], P = .80).

Conclusions: Patients with 22q11-related genetic syndromes and cleft palate undergo palatoplasty later and are more likely to require secondary VPI surgery than matched nonsyndromic peers. They also experience higher rates of intraoperative and postoperative complications after cleft palate repair, while orthognathic surgery rates and neighborhood-level deprivation appear similar. These findings support the need for individualized perioperative planning and close longitudinal speech-focused follow-up in this medically complex population.