Clinical Impact of Genetic Diagnosis of Sensorineural Hearing Loss in Adults

Autores de IDIVAL

• Patricia Corriols Noval

  Autor

• Eugenia Lopez Simon

  Autor

• 

  Rocío González Aguado

  Autor

• Carmelo Morales Ángulo

  Autor

Autores ajenos al IDIVAL

• Cadiñanos J
• Diñeiro M
• Capín R
• Costales Marcos M
• Cabanillas Farpón R

Unidades

• CICLO CELULAR, CÉLULAS MADRE Y CÁNCER

  

  Investigador Responsable

  Alberto Gandarillas Solinis

Abstract

Hypothesis: Adult genetic sensorineural hearing loss (SNHL) may be underestimated. Background: The diagnosis of genetic hearing loss is challenging, given its extreme genetic and phenotypic heterogeneity, particularly in adulthood. This study evaluated the utility of next-generation sequencing (NGS) in the etiological diagnosis of adult-onset SNHL. Materials and Methods: Adults (>16 yr old) with SNHL were recruited at the Otolaryngology Department at Marques de Valdecilla University Hospital (Spain). Environmental factors, acoustic trauma, endolymphatic hydrops, and age-related hearing loss were excluding criteria. An NGS gene panel was used, including 196 genes (OTOgenics v3) or 229 genes (OTOgenics v4) related to syndromic and nonsyndromic hearing loss.ResultsSixty-five patients were included in the study (average age at the onset of SNHL, 41 yr). Fifteen pathogenic/likely pathogenic variants considered to be causative were found in 15 patients (23% diagnostic yield) in TECTA (4), KCNQ4 (3), GJB2 (2), ACTG1 (1), COL2A1 (1), COCH (1), COCH/COL2A1 (1), STRC (1), and ABHD12 (1). Three patients had syndromic associations (20% of patients with genetic diagnosis) that had not been previously diagnosed (two Stickler type I and one polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, cataract syndrome). Seven variants of unknown significance were found in COL11A1 (1), GSMDE (2), DNTM1 (1), SOX10 (1), EYA4 (1), and TECTA (1). Conclusion: NGS gene panels can provide diagnostic yields greater than 20% for adult SNHL, with a significant proportion of variant of unknown significance that could potentially contribute to increasing diagnostic output. Identifying a genetic cause enables genetic counseling, provides prognostic information and can reveal unrecognized syndromes contributing to an accurate management of their associated manifestations.

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