Next-generation sequencing improves precision medicine in hearing loss.

Background: An early etiological diagnosis of hearing loss positively impacts children's quality of life including language and cognitive development. Even though hearing loss associates with extremely high genetic and allelic heterogeneity, several studies have proven that Next-Generation Sequencing (NGS)-based gene panel testing significantly reduces the time between onset and diagnosis. Methods: In order to assess the clinical utility of our custom NGS GHELP panel, the prevalence of pathogenic single nucleotide variants, indels or copy number variants was assessed by sequencing 171 nuclear and 8 mitochondrial genes in 155 Spanish individuals with hearing loss. Results: A genetic diagnosis of hearing loss was achieved in 34% (52/155) of the individuals (5 out of 52 were syndromic). Among the diagnosed cases, 87% (45/52) and 12% (6/52) associated with autosomal recessive and dominant inheritance patterns respectively; remarkably, 2% (1/52) associated with mitochondrial inheritance pattern. Although the most frequently mutated genes in this cohort were consistent with those described in the literature (GJB2, OTOF or MYO7A), causative variants in less frequent genes such as TMC1, FGF3 or mitCOX1 were also identified. Moreover, 5% of the diagnosed cases (3/52) were associated with pathogenic copy number variants. Conclusion: The clinical utility of NGS panels that allows identification of different types of pathogenic variants-not only single nucleotide variants/indels in both nuclear and mitochondrial genes but also copy number variants-has been demonstrated to reduce the clinical diagnostic odyssey in hearing loss. Thus, clinical implementation of genomic strategies within the regular clinical practice, and, more significantly, within the newborn screening protocols, is warranted.

Otosclerosis among patients with dizziness.

OBJECTIVE: The objective of this study was to identify patients with otosclerosis and to characterize its clinical presentation among patients examined at our hospital with vertigo as the primary and most distressing symptom. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary medical center. PATIENTS: This study involved 40 patients suffering from dizziness and diagnosed with otosclerosis. METHODS: At inclusion, the clinical status, as well as auditory (pure tone hearing level and speech audiometry, impedancemetry) and vestibular function (bedside, nystagmography, caloric test and rotator chair testing) were assessed. The results were analyzed using parametric and non-parametric tests, and the chi2 test. RESULTS: The clinical presentation was diverse: 12 patients with Menière's syndrome (30%); 11 patients with spontaneous recurrent vertigo without hearing fluctuation (27.5%); 13 patients with positional vertigo (32.5%); 3 patients with chronic unrelapsing imbalance (7.5%); and 1 patient with acute unilateral vestibulopathy (2.5%). There was a lag between the detection of hearing loss and the beginning of vertigo attacks or imbalance in all patients. When measured through bone conduction, hearing loss was significantly different in patients with Menière's disease, spontaneous recurrent vertigo and positional vertigo. CONCLUSIONS: Dizziness, although frequent in patients with otosclerosis is rarely a cause for specific clinical assessment. There is a lag between the patient's perception of hearing loss and the initiation of vestibular symptoms, and it is not associated with any specific clinical disorder Otosclerosis can be found as any one of the most common vestibular disorders and in general, vestibular function tests reveal a more severe vestibular dysfunction than in the idiopathic forms. LEVEL OF EVIDENCE: 2A.

[Surgery for Atresia auris. Retrospective study of our results and correlation with Jahrsdoerfer prognostic criterium]. / Cirugía de la Atresia auris. Estudio retrospectivo de nuestros resultados y correlación con los criterios pronósticos de Jahrsdoerfer.

OBJECTIVES: The study goal was to evaluate the hearing follow up results in patients who underwent surgery for congenital aural atresia. We studied hearing results and correlated them with Jahrsdoerfer prognostic classification. Protocols management of unilateral and bilateral atresia auris are written considering to our results and other authors. METHODS: We conducted a retrospective review of 12 ears who underwent surgery for congenital aural atresia between 1989 and 2002. CT scan was used to evaluate Jahrsdoerfer prognostic classification and the correlation with the hearing results. RESULTS: There are significant statistical differences (p = 0.003) in air-bone gap closure before and after surgery, also a lineal significant correlation (p = 0.016) between Jahrsdoerfer prognostic classification and air-bone gap closure. CONCLUSION: Atresiaplasty surgery in individuals with congenital aural atresia can yield good hearing results in selected cases.

Cirugía de la atresia auris. Estudio retrospectivo de nuestros resultados y correlación con los criterios pronósticos de Jahrsdoerfer / Surgery for atresia auris. Retrospective study of our results and correlation with Jahrsdoerfer prognostic criterium

Objetivos: Evaluar los resultados auditivos de una muestra de pacientes diagnosticados de atresia auris intervenidos de cirugía otológica. Estudiamos la correlación de los resultados auditivos con la clasificación pronóstica de Jahrsdoerfer. Con nuestros resultados y los de otros autores, proponemos un algoritmo terapéutico en la atresia auris unilateral y bilateral. Métodos: Realizamos una revisión retrospectiva de 12 oídos que hemos intervenido por atresia auris entre 1989 a 2002. Mediante estudio de la TC, valoramos los criterios pronósticos de Jahrsdoerfer correlacionándolos con los resultados obtenidos en el estudio audiométrico antes y después de la cirugía. Resultados: Existen diferencias estadísticamente significativas (p=0,003) en el cierre del umbral tonal diferencial (UTD) antes y después de la cirugía y una correlación lineal significativa (p=0,016) entre la puntuación obtenida en la clasificación de Jahrsdoerfer y el cierre del UTD. Conclusiones: La cirugía de la atresia auris proporciona buenos resultados auditivos en casos seleccionados (AU)

OBJECTIVES: The study goal was to evaluate the hearing follow up results in patients who underwent surgery for congenital aural atresia. We studied hearing results and correlated them with Jahrsdoerfer prognostic classification. Protocols management of unilateral and bilateral atresia auris are written considering to our results and other authors. METHODS: We conducted a retrospective review of 12 ears who underwent surgery for congenital aural atresia between 1989 and 2002. CT scan was used to evaluate Jahrsdoerfer prognostic classification and the correlation with the hearing results. RESULTS: There are significant statistical differences (p = 0.003) in air-bone gap closure before and after surgery, also a lineal significant correlation (p = 0.016) between Jahrsdoerfer prognostic classification and air-bone gap closure. CONCLUSION: Atresiaplasty surgery in individuals with congenital aural atresia can yield good hearing results in selected cases (AU)