OBJECTIVES/HYPOTHESIS: To estimate the risk of surgically treated middle ear cholesteatoma in individuals with a nonsyndromic orofacial cleft and in their siblings compared with the general population.

STUDY DESIGN: Historical cohort study.

METHODS: Using the unique civil registration number for linkage, data from three national registers were used for the Danish 1936-2009 birth cohorts. Hazard ratios (HRs) were estimated with Cox regression analyses using age as the underlying time variable. Individuals were followed from January 1, 1977 until time of surgically treated cholesteatoma, and censored at emigration, death, or end of follow-up (December 31, 2010).

RESULTS: A total of 8,593 individuals with nonsyndromic orofacial cleft and 6,989 siblings were identified, undergoing 201 and 21 first-time cholesteatoma surgeries, respectively. A 5% random sample of the Danish population comprising 249,708 persons without an orofacial cleft was created, and 175,724 siblings to these persons were identified. These controls underwent 485 and 332 first-time cholesteatoma surgeries, respectively. For individuals with cleft lip and palate the HR for cholesteatoma surgery was 14 (95% confidence interval [CI], 12-18) and for individuals with cleft palate the HR was 20 (95% CI, 16-24) when compared with the random sample. In siblings of individuals with cleft palate, the HR for cholesteatoma surgery was 2.1 (95% CI, 1.1-4.1) when compared with siblings of the random sample.

CONCLUSIONS: A 20-fold increase in the risk of cholesteatoma was found in individuals with cleft palate, whereas cleft lip did not pose a risk of cholesteatoma. Furthermore, the study indicates an increased risk of cholesteatoma in unaffected siblings of individuals with cleft palate.

LEVEL OF EVIDENCE: 2b Laryngoscope, 125:1225-1229, 2015.