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Colm Madden, FRCSI; Mark Halsted, MD; Jareen Meinzen-Derr, PhD, MPH; Dianna Bardo, MD; Mark Boston, MD; Ellis Arjmand, MD; Carla Nishimura, BS; Tao Yang, PhD; Corning Benton, MD; Vijay Das, MD; Richard Smith, MD; Daniel Choo, MD; John Greinwald, MD

Arch Otolaryngol Head Neck Surg. 2007;133(2):162-168.

Objective  To correlate genetic and audiometric findings with a detailed radiologic analysis of the temporal bone in patients with enlarged vestibular aqueduct (EVA) to ascertain the contribution of SLC26A4 gene mutations to this phenotype.

Design  A retrospective review of patients with EVA identified in a database of pediatric hearing-impaired patients.

Setting  A tertiary care pediatric referral center.

Patients  Seventy-one children with EVA and screening results for SLC26A4 mutations.

Main Outcome Measures  Genetic screening results, audiometric thresholds, and radiographic temporal bone measurements.

Results  Seventy-one children with EVA were screened for SLC26A4 mutations. Mutations were found in 27% of children overall, while only 8% had biallelic mutations. The mean initial pure-tone average (PTA) was 59 dB; the mean final PTA was 67 dB. A bilateral EVA was found in 48 (67%) of the children; a unilateral EVA was found in 23 (33%). Progressive hearing loss (in at least 1 ear) was seen in 29 (41%) of the patients. The strongest genotype-phenotype interaction was seen in children with a bilateral EVA. Among children with SLC26A4 mutations, there was a significantly wider vestibular aqueduct at the midpoint and a wider vestibule width (P<.05) than in children without the mutation. Among patients with a bilateral EVA, children with any SLC26A4 mutation were more likely to have a more severe final PTA (64 dB vs 32 dB), larger midpoint measurement (2.1 vs 1.1 mm), and larger operculum measurement (3.0 vs 2.0 mm) than those without the mutation in their better-hearing ear (P<.05).

Conclusions  In a population of pediatric patients with an EVA and hearing loss, SLC26A4 mutations are a contributor to the phenotype. Our data suggest that other genetic factors also have important contributions to this phenotype. The presence of an abnormal SLC26A4 allele, even in the heterozygous state, was associated with greater enlargement of the vestibular aqueduct, abnormal development of the vestibule, and possibly a stable hearing outcome.

Author Affiliations: Department of Audiovestibular Medicine, Manchester Royal Infirmary, Manchester, England (Drs Madden and Das); Neuroradiology Section, Division of Radiology (Drs Halsted and Benton), Center for Hearing and Deafness Research, Division of Pediatric Otolaryngology (Drs Meinzen-Derr, Boston, Arjmand, Choo, and Greinwald), and Center for Epidemiology and Biostatistics (Dr Meinzen-Derr), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Otolaryngology, Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati (Drs Halsted, Arjmand, Benton, Choo, and Greinwald); Department of Radiology, University of Chicago, Chicago, Ill (Dr Bardo); and Molecular Otolaryngology Research Laboratories, Department of Otolaryngology, University of Iowa, Iowa City (Ms Nishimura and Drs Yang and Smith).

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