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Updated: Aug 6, 2026
Neuro-rehabilitation Approach for Sudden Sensorineural Hearing Loss
Published on: January 25, 2016
Connexin 26 studies in patients with sensorineural hearing loss
M A Kenna1, B L Wu, D A Cotanche
1Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USA. margaret.kenna@tch.harvard.edu
Insights
Connexin 26 (Cx26) mutations are a common cause of sensorineural hearing loss (SNHL) and mixed hearing loss (MHL) in children. Early genetic testing for Cx26 mutations is recommended for accurate diagnosis and management.
Area of Science:
- Genetics
- Otolaryngology
- Pediatrics
Background:
- Sensorineural hearing loss (SNHL) and mixed hearing loss (MHL) are significant causes of disability in children.
- Connexin 26 (Cx26) gene mutations are known to be associated with hearing loss, but their spectrum and phenotypic impact require further elucidation.
- Identifying the genetic basis of hearing loss is crucial for diagnosis, prognosis, and potential therapeutic strategies.
Purpose of the Study:
- To investigate the prevalence and types of connexin 26 (Cx26) gene mutations in children diagnosed with SNHL or MHL.
- To correlate specific Cx26 mutations with the clinical phenotypes of hearing loss observed in pediatric patients.
- To assess the diagnostic utility of Cx26 mutation screening in children with unexplained hearing loss.
Main Methods:
- Prospective genetic analysis of the entire coding region of the Cx26 gene in children with SNHL or MHL.
- Enrollment of 107 patients from 99 families with hearing loss of unknown etiology.
- Mutation screening included identification of previously reported and novel Cx26 mutations, differentiating between biallelic and single mutations.
Main Results:
- Cx26 mutations were identified in 30% of probands, with 18 cases showing biallelic mutations (homozygous or compound heterozygous) and 12 cases with single mutations.
- Twelve known and three novel Cx26 mutations were detected, including 35delG, 167delT, and E129K.
- Hearing loss severity in patients with biallelic Cx26 mutations varied from unilateral high-frequency to bilateral profound, with a notable incidence of milder hearing loss compared to prior studies. Temporal bone abnormalities were observed in four children.
Conclusions:
- Connexin 26 (Cx26) mutations are a frequent genetic cause of SNHL and MHL in the pediatric population.
- Biallelic Cx26 mutations are strongly implicated in causing SNHL, while the pathogenicity of single mutations remains less certain.
- Early screening for Cx26 mutations is recommended for children presenting with SNHL or MHL to facilitate timely diagnosis and management.
Objective:
To determine the spectrum of connexin 26 (Cx26) mutations and their phenotypes in children with sensorineural hearing loss (SNHL) or mixed hearing loss (MHL).
Design:
Children with SNHL or MHL were prospectively tested for mutations in the entire coding region of the Cx26 gene.
Patients:
Children with SNHL or MHL with no obvious etiology for the hearing loss.
Results:
Between December 1, 1998, and July 1, 2000, 107 patients with SNHL or MHL from 99 families underwent Cx26 testing. Most patients were aged 1 week to 16 years (61 boys and 46 girls). Thirty (30%) of 99 probands had Cx26 mutations: biallelic mutations were detected in 18 (9 homozygous and 9 compound heterozygous) and single mutations were detected in 12. Twelve previously reported mutations (35delG, 167delT, E47X, L90P, M34T, G12V, V37I, R143W, V84L, V153I, V27I, and 310del14) and 3 novel mutations (E129K, T8M, and N206S) were found. Hearing loss in patients with biallelic Cx26 mutations ranged from unilateral high frequency to bilateral profound. Four children, 2 with biallelic mutations, had temporal bone abnormalities.
Conclusions:
Connexin 26 mutations are common in children with SNHL, and it is likely that the homozygous and compound heterozygous mutations cause the SNHL. However, pathogenicity is less certain when only a single Cx26 mutation is present. Patients with biallelic Cx26 mutations had a slightly higher incidence of milder hearing loss than in previous studies. Children with SNHL or MHL should be tested for Cx26 mutations early in their evaluation.
