Genetic and Clinical Predictors of Hearing Loss Among Patients with CHARGE Syndrome

Objective: CHARGE syndrome (CS) is a genetic disorder caused by pathogenic variants within chromodomain helicase DNA-binding protein 7 (CHD7). The classical presentation includes coloboma, congenital heart defects, atresia of the choanae, retardation of development, genital hypoplasia, and ear anomalies. Clinical presentation varies widely by type and severity. Structural anomalies of the ear cause hearing loss in 93 percent of individuals with CS. Factors to predict the type and degree of hearing loss among individual patients with CS have not been identified. Identifying factors would ensure patients receive early intervention and allow health care providers to accurately counsel on expectations. Research Design: To identify factors correlated with certain types and degrees of hearing loss, a retrospective chart review of 57 pediatric individuals with CHD7 disease-causing variants from the CHARGE Center at Cincinnati Children's Hospital Medical Center was conducted. All data were manually extracted from participants' medical records, as well as the CHARGE Clinic REDcap database. Type and degree of hearing loss were compared to the type of CHD7 variant and craniofacial anomalies. Results: Within our cohort, 97 percent of individuals experienced hearing loss (HL), with sensorineural (SNHL) being the most common type. Eighty-three percent experienced severe-to-profound HL in at least one ear, a higher prevalence than previously reported. Temporal bone scan results were available for 34 participants with HL, and structural anomalies were seen in 79 percent of individuals. Type of HL did correlate with CHD7 variant type (n = 100, p = 0.002). The most striking relationship is an increased risk of SNHL with CHD7 haploinsufficiency due to nonsense or frameshift variants. Conclusions: Regardless of the type or location of CHD7 variant, patients with CS are at risk for HL and should undergo temporal bone analysis as part of their initial workup. Such findings continue to expand providers' understanding of CS and will improve the management of patients.