Diagnostic Yield in Childhood-Onset Hearing Loss: A Meta-Analysis and Systematic Review

Area of Science:

• Genetics and Genomics
• Otolaryngology
• Pediatrics

Background:

• Hearing loss is a common congenital condition with a significant genetic component.
• Genetic testing, including whole-exome sequencing (WES) and targeted gene panels, is increasingly used to diagnose the cause of hearing loss in children.
• Understanding the diagnostic yield of these genetic tests is crucial for clinical decision-making and healthcare policy.

Purpose of the Study:

• To systematically review and meta-analyze the diagnostic yield of WES and targeted-panel sequencing in pediatric hearing loss.
• To compare the diagnostic yield between bilateral and unilateral hearing loss.
• To contextualize the diagnostic yield of hearing loss genetic testing against other common pediatric genetic conditions.

Main Methods:

• Systematic literature search of PubMed, Google Scholar, and Cochrane Library for relevant studies.
• Inclusion criteria: cohorts >50 families, WES or targeted-panel sequencing, data on diagnostic yield.
• Exclusion criteria: pre-screening for common genes without final analysis, syndromic hearing loss focus, lack of yield data.
• Meta-analysis using a random-effects model of single proportions to pool diagnostic yield.

Main Results:

• The pooled diagnostic yield for bilateral hearing loss was approximately 47% across both WES and targeted-panel sequencing.
• The diagnostic yield for unilateral hearing loss was significantly lower, around 5%.
• The diagnostic yield for bilateral hearing loss surpasses that of conditions like epilepsy and intellectual disability.

Conclusions:

• Whole-exome and targeted-panel sequencing are effective diagnostic tools for bilateral pediatric hearing loss, with a substantial diagnostic yield.
• The diagnostic yield for unilateral hearing loss is considerably lower, suggesting different genetic underpinnings or testing limitations.
• Findings support the integration of genetic testing for bilateral hearing loss into clinical guidelines and inform healthcare policy and funding decisions.