Cleft Palates Predict Higher Risk for Surgically Treated Cholesteatoma

What risk of surgically treated middle ear cholesteatoma do individuals with a nonsyndromic orofacial cleft and their siblings face compared with the general population?

Background: Individuals with an orofacial cleft have a predisposition to middle ear disease. Impaired Eustachian tube function with negative middle ear pressure may cause a retraction pocket, generally considered a main component in cholesteatoma development. In unaffected relatives of cleft lip (CL) cases, ultrasonography has demonstrated orbicularis oris muscle defects that have been suggested as an expanded CL phenotype. Due to the rarity of orofacial clefts and cholesteatomas, epidemiologic studies require large study populations and long observation periods to analyze possible correlations.

Study design: Historical cohort study of 8,593 nonsyndromic individuals from Jan. 1, 1977, until time of surgically treated cholesteatoma—and censored at emigration, death, or end of follow-up (Dec. 31, 2010)—plus a total of 6,989 siblings.

Setting: Three national registers for the Danish 1936–2009 birth cohorts.

Synopsis: Kaplan-Meier plots showed a considerably increased risk of first surgically treated middle ear cholesteatoma (STMEC1) in the cleft lip and palate (CLP) and cleft palate (CP) groups, but not in the CL group. Cox regression analysis demonstrated a 20-fold increased risk of STMEC1 in the CP group and a 14-fold increased risk in the CLP group, but no increased risk in the CL group. There was a decreasing risk of STMEC1 with increasing birth decade that was only significant for the earliest birth decades. Kaplan-Meier plots showed an increased STMEC1 risk in siblings of CP cases. Cox regression analysis demonstrated a 2.1-fold increased risk of STMEC1 in siblings of CP cases, but no increased risk in siblings of CL or CLP cases. There was strong evidence of an almost 20-fold increased risk of STMEC1 for the CP group but not for the CL group. Limitations included a risk of register study misclassification, the possible incorrect inclusion of patients operated on before 1977 as new STMEC1 cases, a limitation of the National Patient Register’s data content to outpatients from 1995 onward, and possible discrepancies in the criteria used for making a cholesteatoma diagnosis between surgeons.

Bottom line: A 20-fold increase in cholesteatoma risk was found in CP individuals, while CL did not pose this risk; furthermore, there was an increased risk of cholesteatoma in unaffected siblings of CP individuals.

Citation: Djurhuus BD, Skytthe A, Faber CE, Christensen K. Cholesteatoma risk in 8,593 orofacial cleft cases and 6,989 siblings: a nationwide study. Laryngoscope. 2015;125:1225-1229.