INTRODUCTION Studies suggest that nonsyndromic cleft lip and palate (NSCLP) is polygenic with variable penetrance, presenting a challenge in identifying all causal genetic variants. Despite relatively high prevalence of NSCLP among Amerindian populations, no large whole exome sequencing (WES) studies have been completed in this population. OBJECTIVE Identify candidate genes with rare genetic variants for NSCLP in a Honduran population using WES. METHODS WES was performed on two to four members of 27 multiplex Honduran families. Genetic variants with a minor allele frequency > 1% in reference databases were removed. Heterozygous variants consistent with dominant disease with incomplete penetrance were ascertained, and variants with predicted functional consequence were prioritized for analysis. Pedigree-specific p-values were calculated as the probability of all affected members in the pedigree being carriers, given that at least one is a carrier. RESULTS Preliminary results identified 3727 heterozygous rare variants; 1282 were predicted to be functionally consequential. Twenty-three genes had variants of interest in ≥3 families, where some genes had different variants in each family, giving a total of 50 variants. Variant validation via Sanger sequencing of the families and unrelated unaffected controls excluded variants that were sequencing errors or common variants not in databases, leaving four genes with candidate variants in ≥3 families. Of these, candidate variants in two genes consistently segregate with NSCLP as a dominant variant with incomplete penetrance: ACSS2 and PHYH. CONCLUSION Rare variants found at the same gene in all affected individuals in several families are likely directly related to NSCLP.

4 Laryngoscope, 126:1397-1403, 2016.

Clinical features may be used to predict the likelihood of a patient obtaining ML. Nomograms may be useful to counsel patients who would benefit from early definitive surgery.

Objective To examine the relationship among frailty index, hearing measures, and hearing-related quality of life (QOL) in older recipients of cochlear implants. Study Design Cross-sectional survey. Setting Academic medical center. Methods Adults aged ≥65 years at the time of receiving cochlear implants between July 13, 2000, and April 3, 2019, were asked to complete a questionnaire on hearing-related QOL. Chart review was performed to identify patients’ characteristics. Correlations were calculated between frailty index and audiologic outcome measures as well as between speech recognition scores and QOL scores. Linear regression models were developed to examine the impact of clinical characteristics, frailty index, and hearing measures on hearing-related QOL. Results Data for 143 respondents were included. The mean age was 80.7 years (SD, 7.1), with a mean 27.8 years of hearing loss (SD, 17.4) before implantation. The mean frailty index was 11.1 (SD, 10.6), indicating that patients had 1 or 2 of the measured comorbidities on average. No correlation was found between lower frailty index (better health) and hearing scores, including pure tone averages (PTAs) and speech recognition scores. Lower frailty index and larger improvement in PTA after cochlear implantation predicted better QOL scores on univariate analysis (respectively, P = .002, β = −0.42 [95% CI, −0.68 to −0.16]; P = .008, β = −0.15 [95% CI, −0.26 to −0.04]) and multivariate analysis ( P = .047, β = −0.28 [95% CI, −0.55 to −0.01]; P = .006, β = −0.16 [95% CI, −0.28 to −0.05]). No speech recognition scores correlated with QOL after cochlear implantation. Conclusions Frailty index does not correlate with hearing scores after cochlear implantation in older adults. Lower frailty index and more improvement in PTA predict better QOL scores after cochlear implantation in older adults.

OBJECTIVE: To estimate long-term prevalence of new dysphagia-related diagnoses in in a large cohort of head and neck cancer survivors. STUDY DESIGN: Retrospective cohort SETTING: Population-based SUBJECTS AND METHODS: 1901 adults diagnosed with head and neck cancer between 1997 and 2012 with at least 3 years of follow up were compared with 7,796 controls matched for age, sex and birth state. Prevalence of new dysphagia-related diagnoses and procedures and hazard ratio compared to controls were evaluated in patients 2–5 years and 5 years and beyond after diagnosis. Risk factors for the development of these diagnoses were analyzed. RESULTS: Prevalence of new diagnosis and hazard ratio compared to controls remained elevated for all diagnoses throughout the time periods investigated. The rate of aspiration pneumonia was 3.13% at 2–5 years increasing to 6.75% at 5 or more years, with hazard ratios of 9.53 (95% CI 5.08 −17.87) and 12.57 (7.17–22.04) respectively. Rate of gastrostomy tube placement increased from 2.82% to 3.32% with hazard ratio remaining elevated from 51.51 (13.45 – 197.33) to 35.2 (7.81–158.72) over the same time period. The rate of any dysphagia-related diagnosis or procedure increased from 14.9% to 26% with hazard ratio remaining elevated from 3.32 (2.50–4.42) to 2.12 (1.63–2.75). Treatment with radiation therapy and age over 65 were associated with increased hazard ratio for dysphagia-related diagnoses. CONCLUSION: Our data supports our hypothesis that new dysphagia-related diagnoses continue to occur at clinically meaningful levels in long-term head and neck cancer survivors beyond 5 years after diagnosis.