Molecular Genetic Advances in Semicircular Canal Abnormalities and Sensorineural Hearing Loss: A Report of 16 Cases

Abstract

The study goals were (1) to determine if the degree and pattern of semicircular canal dysmorphology and the presence or absence of a cochlea in patients with congenital sensorineural hearing loss predict audiologic outcome, severity, or the frequencies involved and (2) to review the recent advances in molecular genetics of the semicircular canals and correlate this information with audiologic and anatomic patterns seen in our series of patients. We conducted a retrospective study at a tertiary care center with a large otologic and cochlear implant service. The study population consisted of 16 patients with congenital sensorineural hearing loss in 28 congenitally malformed inner ears consisting of semicircular canal dysplasia or aplasia, with or without cochlear malformation. History, physical examination, computed tomography scans, and serial audiograms were reviewed. Factors analyzed included other phenotypic dysmorphology characteristic of syndromes, audiometric configuration, severity and type of hearing loss, and the presence of associated inner ear anomalies other than the vestibular system. An extensive review of the literature regarding molecular genetic factors in semicircular canal anomalies, with or without cochlear abnormalities, was performed. Sixteen patients (31 ears) were identified with profound sensorineural hearing loss and semicircular canal abnormalities. Only 3 patients had known syndromes, although 4 patients had other congenital anomalies. Most radiographic detectable abnormalities were bilateral. Audiograms of the patients demonstrated pure tone averages between 90 and 100 dB in the affected ears with few exceptions. No correlation was found between type and severity of malformation of either the cochlea or semicircular canals with the severity of hearing loss. There was no stepwise progression of hearing loss increasing malformation severity. Seven of the 16 patients received cochlear implants. Of these 7, 3 patients had cochlear hypoplasia and 1 patient had a common cavity deformity. Audiologic follow-up on all 7 patients revealed improvement in both speech assessment threshold and pure tone average. Presence or absence of the cochlea was not a factor in outcome after cochlear implantation. We have assembled the largest series of patients with semicircular canal dysmorphology, with or without various cochlear abnormalities. Our study failed to correlate the type and severity of semicircular canal malformation with any specific audiologic outcome. The variation in hearing loss severity and pattern even in patients with similar bony radiographic findings must be explained by other non-radiologically detectable defects, likely abnormalities in membranous labyrinthine development. New molecular genetic discoveries have linked specific genes to the development of certain inner ear structures in mice studies. The independent development of the individual semicircular canals in relation to the cochlea and vestibule and the variability in hearing loss suggest a more complex embryologic process than merely an arrest in development as previously thought. As genetic studies are extended into humans, we will likely be able to stratify these patients by molecular defect and severity of hearing loss.