RESUMO
Autosomal dominant non-syndromic hearing loss (ADNSHL) displays gene-specific progression of hearing loss, which is amenable to sequential audioprofiling. We sought to refine the natural history of ADNSHL by examining audiometric data in 5-year increments. 2175 audiograms were included from four genetic causes of ADNSHL-KCNQ4 (DFNA2), GSDME (DFNA5), WFS1 (DFNA6/14/38), and COCH (DFNA9). Annual threshold deterioration (ATD) was calculated for each gene: for the speech-frequency pure tone average, the ATD, respectively, was 0.72 dB/year, 0.94 dB/year, 0.53 dB/year, and 1.41 dB/year, with the largest drops occurring from ages 45-50 (0.89 dB/year; KCNQ4), 5-10 (1.42 dB/year; GSDME), 40-45 (0.83 dB/year; WFS1), and 50-55 (2.09 dB/year; COCH). 5-year interval analysis of audiograms reveals the gene specific natural history of KCNQ4, GSDME, WFS1 and COCH-related progressive hearing loss. Identifying ages at which hearing loss is most rapid informs clinical care and patient expectations. Natural history data are also essential to define outcomes of clinical trials that test novel therapies designed to correct or ameliorate these genetic forms of hearing loss.
Assuntos
Surdez , Perda Auditiva Neurossensorial , Perda Auditiva , Audiometria , Surdez/genética , Proteínas da Matriz Extracelular/genética , Perda Auditiva/genética , Perda Auditiva Neurossensorial/genética , Humanos , Canais de Potássio KCNQ/genética , Pessoa de Meia-Idade , LinhagemRESUMO
Pathogenic variations in the OTOF gene are a common cause of hearing loss. To refine the natural history and genotype-phenotype correlations of OTOF-related auditory neuropathy spectrum disorders (ANSD), audiograms and distortion product otoacoustic emissions (DPOAEs) were collected from a diverse cohort of individuals diagnosed with OTOF-related ANSD by comprehensive genetic testing and also reported in the literature. Comparative analysis was undertaken to define genotype-phenotype relationships using a Monte Carlo algorithm. 67 audiograms and 25 DPOAEs from 49 unique individuals positive for OTOF-related ANSD were collected. 51 unique OTOF pathogenic variants were identified of which 21 were missense and 30 were loss of function (LoF; nonsense, splice-site, copy number variants, and indels). There was a statistically significant difference in low, middle, and high frequency hearing thresholds between missense/missense and LoF/missense genotypes as compared to LoF/LoF genotypes (average hearing threshold for low, middle and high frequencies 70.9, 76.0, and 73.4 dB vs 88.5, 95.6, and 94.7 dB) via Tukey's test with age as a co-variate (P = 0.0180, 0.0327, and 0.0347, respectively). Hearing declined during adolescence with missense/missense and LoF/missense genotypes, with an annual mid-frequency threshold deterioration of 0.87 dB/year and 1.87 dB/year, respectively. 8.5% of frequencies measured via DPOAE were lost per year in individuals with serial tests. Audioprofiling of OTOF-related ANSD suggests significantly worse hearing with LoF/LoF genotypes. The unique pattern of variably progressive OTOF-related autosomal recessive ANSD may be amenable to gene therapy in selected clinical scenarios.
Assuntos
Surdez , Perda Auditiva Central , Perda Auditiva Central/diagnóstico , Perda Auditiva Central/genética , Humanos , Proteínas de Membrana/genética , MutaçãoRESUMO
Objectives: The presence of a catheter required for contrast infusion during sialography obscures imaging of the distal duct. Static imaging via cone beam computed tomography and magnetic resonance sialography fails to address changes that occur dynamically to the anatomy of the flexible salivary ductal system. We aim to identify dynamic changes to the parotid gland by introducing a novel approach to analyze the full extent of Stensen's duct based on dynamic infusion digital sialography. Methods: Retrospective chart review of a single-center consecutive series of 409 parotid sialograms performed between April 2008 and June 2023 permitted selection of a contemporary series including seven normal sialograms and seven sialograms with stricture(s). Dynamic (fluoroscopic) infusion (iopamidol/gadolinium) sialograms were assessed through blinded review by two radiologists employing the institution's picture archiving and communication (PACS) system (©2023 Koninklijke Philips N.V., Amsterdam, Netherlands). Measurements determined changes, in two dimensions, to the angle of the masseteric bend and duct length while the catheter was in place (repose), during catheter withdrawal (stretch), and during recoil after withdrawal. Differences in median lengths and angles of Stensen's duct between the three time points were compared using Wilcoxon matched-pairs signed rank and Mann-Whitney tests. Results: Fourteen patients [median age (IQR), 55 years (24.7); 10 women] were evaluated. The median angle of the masseteric bend was 117.7° in repose versus 155.4° during catheter withdrawal (P < .001, n = 14). The median distance measured from the Stensen's duct orifice to the first major ductal bifurcation was 81.5 mm (IQR = 12.3) in repose. The median percent increase in length from repose to stretch was 6.3% (P < .001, n = 14). Conclusions: Dynamic infusion digital sialography with fluoroscopic recording during catheter removal permits assessment of the distal duct unobstructed by the presence of a catheter. The technique also identifies the dynamic nature and varying length and angulation of Stensen's duct.
RESUMO
OBJECTIVES/HYPOTHESIS: To apply a novel sialography classification system to identify parotid and submandibular ductal findings following I-131 therapy and to assess correlates to dose and duration of symptoms. STUDY DESIGN: Retrospective single-center case series. METHODS: Patients who underwent sialography between February 2008 and February 2019 after previously receiving I-131 treatment were identified via a retrospective chart review. Their sialograms were systematically evaluated and scored by applying the Iowa parotid sialogram scale to also include submandibular gland analysis. RESULTS: From 337 sialograms, 30 (five submandibular, 25 parotid) underwent analysis. Ductal stenosis was identified in all sialograms and was graded as moderate (>50%-75%) in 7/30 cases and severe (>75%) in 15/30 cases. The distal (main) duct was narrowed in 23/30 cases. No association was identified between degree of ductal stenosis and I-131 dose (P = .39), age (P = .81), or time from I-131 therapy to sialogram (P = .97). CONCLUSIONS: The Iowa parotid sialogram scale was successfully applied to report abnormalities of the parotid and submandibular ductal system. The most common manifestation of I-131-associated sialadenitis was a severe stenosis within the distal salivary duct. No statistically significant association was found between degree of ductal stenosis and dose of I-131, age, or duration of symptoms. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1450-E1456, 2021.
Assuntos
Radioisótopos do Iodo/efeitos adversos , Doenças Parotídeas/diagnóstico , Lesões por Radiação/diagnóstico , Sialadenite/diagnóstico , Sialografia/estatística & dados numéricos , Doenças da Glândula Submandibular/diagnóstico , Adulto , Idoso , Relação Dose-Resposta à Radiação , Feminino , Humanos , Radioisótopos do Iodo/administração & dosagem , Masculino , Pessoa de Meia-Idade , Doenças Parotídeas/etiologia , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/efeitos da radiação , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Ductos Salivares/diagnóstico por imagem , Ductos Salivares/efeitos da radiação , Sialadenite/etiologia , Glândula Submandibular/diagnóstico por imagem , Glândula Submandibular/efeitos da radiação , Doenças da Glândula Submandibular/etiologia , Doenças da Glândula Tireoide/radioterapia , Adulto JovemRESUMO
Hearing loss is the most common neurosensory deficit. It results from a variety of heritable and acquired causes and is linked to multiple deleterious effects on a child's development that can be ameliorated by prompt identification and individualized therapies. Diagnosing hearing loss in newborns is challenging, especially in mild or progressive cases, and its management requires a multidisciplinary team of healthcare providers comprising audiologists, pediatricians, otolaryngologists, and genetic counselors. While physiologic newborn hearing screening has resulted in earlier diagnosis of hearing loss than ever before, a growing body of knowledge supports the concurrent implementation of genetic and cytomegalovirus testing to offset the limitations inherent to a singular screening modality. In this review, we discuss the contemporary role of screening for hearing loss in newborns as well as future directions in its diagnosis and treatment.