90 - Treacher Collins Syndrome associated with disproportionate central nervous system, cardiovascular, otologic complications among 895 patients

Treacher Collins syndrome (TCS) is a rare condition that affects the development of the head and face. The syndrome is genetic and its phenotypic expression variable, with several causal variants having been identified. Recent efforts have suggested that TCS abnormalities may extend beyond craniofacial, such as the discovery of a TCS-linked gene also mutated in a hypomyelinating leukodystrophy. However, our ability to quantify these possible additional anomalies is limited by the rarity of TCS, resulting in small sample sizes in existing studies.


Objective:

To compare the rates of selected central nervous system (CNS), cardiovascular, and otologic abnormalities in patients with and without TCS.


 

Design/Methods:

Our retrospective cohort study utilized the TriNetx Analytics Research Network which aggregates deidentified electronic health record data from scores of healthcare systems across the United States. With access to the data of an unprecedented number of affected individuals, we compared the diagnoses of several CNS, cardiovascular, and otologic conditions between patients with (n=895) and without (n = 106,242,186) TCS.


Results:

We found a significantly elevated risk for TCS patients within all three categories (Tables 1-3). Among CNS conditions, dystonia was the most notable, with individuals with TCS over eleven times more likely than those in our unaffected cohort to receive this diagnosis, and over five times more likely to have recurrent seizures.  Those with TCS were at significantly increased risk of many congenital cardiovascular conditions, including atrioventricular septal defect (Relative Risk (RR) 63.1) and Tetralogy of Fallot (RR 49).  Regarding otologic complications, we found the prevalence of conductive hearing loss to be 71.6% within the TCS cohort, and the RR of otitis media infections to be 6.9.


Conclusion(s):

Individuals with TCS have an increased likelihood of central nervous system, cardiovascular, and otologic abnormalities. The craniofacial abnormalities in TCS impair hearing more commonly than previously identified and may put patients at risk for otitis media infections, also found to be notably increased. We postulate that the CNS complications in TCS may be linked to a causal gene also found to be mutated in a leukodystrophy associated with ataxia, cerebellar atrophy, and seizures. Our findings may help researchers to hypothesize the function of the syndrome’s underlying genes, as well as to inform the care of affected individuals.