Treacher Collins Syndrome Associated with Disproportionate Nervous System, Cardiovascular, Otologic Complications Among 1,114 Patients.

OBJECTIVE: To compare the rates of selected nervous system, cardiovascular, and otologic abnormalities in patients with and without Treacher Collins Syndrome (TCS).

DESIGN: Retrospective TriNetX platform cohort study.

SETTING: Aggregated and deidentified electronic health record (EHR) data from across the United States.

PATIENTS, PARTICIPANTS: Patients with TCS (n = 1,114) and a propensity matched control cohort without TCS (n = 1,114 matched from n = 110,368,585).

MAIN OUTCOME MEASURED: Prevalence and relative risk (RR) of selected diagnoses in a propensity-matched cohort.

RESULTS: The RR of congenital malformations of the circulatory system in patients with TCS was 8.5 (95% CI 4.44-16.28). Patients with TCS also had higher rates of otologic abnormalities including conductive hearing loss (RR 44, 95% CI 24-83) and nervous system disorders including movement disorders (RR 2.60, 95% CI 1.27-5.50) and recurrent seizures (RR 4.2, 95% CI 2.12-8.33).

CONCLUSIONS: We found a significantly elevated risk in TCS patients within all three systems. We postulate that the nervous system effects may be the result of one of the TCS-linked genes, for which a mutation has also been associated with progressive ataxia, cerebellar atrophy, hypomyelination, and seizures. As the previously-identified causal genes influence neural crest cells that form the head and face, these cells may also populate cardiac structures, resulting in cardiovascular abnormalities. Finally, the characteristic craniofacial abnormalities identified in TCS impair hearing and are associated with increased risk of otitis media. Our findings may help researchers to hypothesize the function of the genes underlying TCS, as well as to inform the care of affected individuals.