Familial recurrence of tracheoesophageal fistula and associated malformations

Tracheoesophageal fistula (TEF) may occur as an isolated malformation or together with other malformations. To determine the recurrence risk of TEF or associated malformations in children and sibs, and to determine the frequency of associated malformations in index patients, we reviewed the Mayo Clinic records of 204 patients with TEF. Also, questionnaires were sent to patients or relatives. Questions were designed to determine whether the patient and relatives had TEF and/or related organ system (including VACTERL) malformations. The VACTERL association is a disorder characterized by 3 or more of the following: vertebral, anal, cardiac, renal, or radial anomalies, and TEF. One hundred twenty-eight families returned a completed questionnaire, and 140 index patients were ascertained based on complete medical records, questionnaire, and/or autopsy. Forty-one (29.3%) of 140 index patients had TEF with one other VACTERL malformation, and twenty-four (17.1%) of 140 index patients had TEF with at least two other VACTERL malformations. Of the 347 sibs of index patients, 5 (1.4%) had one VACTERL malformation each, including 1 sib with esophageal atresia (EA) without TEF. Of the 41 children of index patients, 1 (2.4%) had TEF plus two other VACTERL malformations; another had one non-TEF VACTERL malformation. From our study, the largest reported population of TEF patients to date, we conclude that: 1) nearly half (46%) of patients with tracheoesophageal fistula will exhibit other VACTERL malformations; 2) the recurrence risk for individuals with TEF to have affected children is 2-3%; and 3) there is an increased risk to relatives of TEF patients to exhibit other VACTERL malformations.