Hearing Status of Children and Adolescents With Familial Adenomatous Polyposis

Patients and Methods

Participants. This research was completed with Institutional Review Board approval. Potential genotype positive subjects were recruited through the clinical polyposis registry of Nationwide Children’s hospital. A screening health questionnaire was administered to assess patient eligibility. Genotype data as well as socioeconomic status indicators, such as maternal education and family income, were gathered through reviewing patient medical charts. Inclusion criteria included children between the ages of 6 and 19 years who had documented mutation in the APC gene but were otherwise healthy and their siblings. Exclusion criteria included children with known hearing loss with known etiology, abnormality of the external ear canal or tympanic membrane, patients with acute illness that may compromise hearing and patients with established autoimmune disease. Four patients were excluded from the study due to known hearing loss due to ototoxicity from previous chemotherapy. Patients who met study criteria were briefed on the study procedures and consented/assented prior to data collection.

A total of 29 children were enrolled in the study and completed the hearing evaluation: 20 FAP children/adolescents [13 male, average age=12.8 years (SD=4.0), age range=6.1-16.9 years] and 9 siblings to serve as controls [4 male, average age=12.2 years (SD=3.3), age range=7.3-16.3 years]. None of the participants reported history of known hearing loss. Children with FAP were divided into three main categories based on genotype as previously described (attenuated, classic and severe) (15). Subject demographics are found in Table I.

Procedures. Hearing evaluations followed nationally established clinical standards for ototoxic monitoring (16). Hearing evaluations included the following standard procedures performed by licensed audiologists: otoscopy, tympanometry, ipsilateral and contralateral acoustic reflex threshold testing, pure-tone audiometry including the extended high-frequency range (250-20,000 Hz), speech perception audiometry, and distortion product otoacoustic emission testing.

Otoscopic examination was completed to evaluate the health of the outer ear and tympanic membrane, and to ensure cerumen occlusion would not negatively affect results of remaining testing procedures. If cerumen was identified as more than partially occluding, brief attempts were made to clear the ear manually. Tympanometry was performed to measure peak compensated static acoustic admittance measures using a 226 Hz probe tone (Grason-Stadler Instruments Middle Ear Analyzer Models TympStar and TympStar Pro, Eden Prairie, MN, USA) calibrated annually to ANSI standard 3.39-R2002. Tympanometry metrics of peak static compliance and middle ear pressure were compared to normative data to evaluate the status of the middle ear (17). Ipsilateral and contralateral acoustic reflex testing was completed via standard clinical protocol using a 226 Hz probe tone and stimulation tones of 500 Hz, 1,000 Hz, and 2,000 Hz. Reflexes were considered present when elicited at 95 dB or less, elevated when elicited at 100 dB or more, and absent if not elicited at the limits of the equipment.

Pure tone audiometry was performed in a double walled sound booth (Industrial Acoustics Company, North Aurora, IL, USA) calibrated re: ANSI S3.1-R2003. Pure tone thresholds were assessed with an audiometer (Grason-Stadler Instruments Clinical Audiometers 61 and AudioStar Pro) calibrated annually re: ANSI S3.6-R2004. Insert earphones (Etymotic Research ER 3A, Elk Grove Village, IL, USA) were used for air conduction pure tone threshold testing from 250-8000 Hz. Supra-aural headphones (Sennheiser HDA 200, Wedemark, Germany) were used for air conduction pure tones above 8000 Hz. A Radioear (B71 or B81, New Eagle, PA, USA) transducer was used for bone conduction pure tones testing. Following clinical standards, threshold search was completed using a Carhart-Jerger Modified Hughson-Westlake procedure (18). Participants responded to pure tone presentations by pushing the patient response button or raising their hand each time they heard a tone. Standard pure-tone average (PTA) was calculated using the mean of 500 Hz, 1000 Hz, and 2000 Hz responses for each ear. High-frequency pure-tone average (HFPTA) was calculated for each participant using the mean of 10,000 Hz, 12,000 Hz, 14,000 Hz, and 16,000 Hz per previous literature (19).

Speech Audiometry followed pure-tone testing and included both speech reception thresholds and speech perception testing. Speech thresholds were obtained with a simple bracketing procedure until three of five words were identified correctly denoting threshold. Speech perception testing was completed using recorded Central Institute for the Deaf (CID-W22) word lists (Auditec, St. Louis, MO, USA) presented at 40 dB SL re: standard PTA via the audiometer. Lastly, distortion product otoacoustic emissions (DPOAE) were recorded using the Biologic Scout clinical otoacoustic emissions machine (Natus, San Carlos, CA, USA) using an ototoxic monitoring protocol measuring emissions between 1500 Hz and 10,000 Hz. DPOAEs at specific frequencies were deemed present when absolute response amplitude was greater than -6 dB and DPOAE-to-noise ratio was at least 6.0 dB.

For statistical analysis, two-sample unpaired t-tests with unequal variances were performed to test for differences between individuals with FAP and those without FAP in PTA and HFPTA. All statistical tests were two-sided and results are reported at their nominal levels. p-values <0.05 were considered statistically significant. All analyses were performed in R version 4.0.