Congenital Hearing Deficit Research Articles

Abnormal sella turcica morphology in individuals with congenital innerear hearing deficits

Introduction: The present study focusses on the interrelationship between medically diagnosed congenital inner-ear hearing deficits and sella turcica morphology. Based on former prenatal studies it is hypothesized that the posterior wall and the floor of the sella turcica are malformed in patients with congenital inner-ear hearing deficits. Material and Methods:The study is based on profile radiographs from 7 patients (10-17 years of age) with congenital inner-ear hearing deficits and hearing aids. The sella turcica was identified and described in these profile radiographs. Results: The posterior walls and the floors of the sella turcicae are malformed in all 7 cases and the anterior wall appear close to normalin all cases. This observation proofs the involvement of the cranialoccipital field in congenital inner ear hearing deficits. Conclusion: The observation of posterior wall and sella floor malformation observed on profile radiographs from patients with congenital inner-ear deficits has seemingly not been published before. In future analyses of profile radiographs, the morphology of the anterior wall, the posterior wall, and the floor of sella turcica should receive specific attention. Absence or malformation of the posterior wall could be a sign of congenital hearing deficit.

Screening for neonatal hearing loss in the Eastern region of United Arab Emirates

The incidence of sensorineural hearing loss among infants in the neonatal intensive unit (NICU) is higher than in normal infants. This study determined the rate of hearing loss in healthy newborns and in NICU patients before hospital discharge at a single institution in the Eastern region of the United Arab Emirates; 96.5% of all eligible infants were screened. Hearing deficit was diagnosed in 25/13 854 healthy newborns (0.18%; 95% CI: 0.12%-0.27%) and 14/826 infants in the NICU (1.7%; 95% CI: 0.9%-2.8%). Although hearing impairment was significantly more common in those admitted to the NICU (RR = 9.4; 95% CI: 4.9-17.9), healthy newborns accounted for 25 of the 39 cases with hearing loss. The rate of congenital hearing deficit was comparable to international data. Universal screening is recommended since selective screening of high-risk infants missed two-thirds of newborns with hearing loss.

In Vivo Delivery of Recombinant Viruses to the Fetal Murine Cochlea: Transduction Characteristics and Long-Term Effects on Auditory Function

Congenital hearing deficits can be caused by a variety of genetic and acquired conditions. Complete reversal of deficits in the peripheral auditory system may require delivery of corrective genes to cochlear progenitor cells. We tested delivery of lentivirus and an array of recombinant adeno-associated viral (AAV) serotypes for efficiency and cellular specificity of transgene expression after in utero delivery to the developing mouse otocyst. Stability of expression and safety with respect to auditory function were then tested in those vectors that had the most favorable in utero cochlear transduction characteristics (AAV2/1, AAV2/8, and lentivirus). AAV2/1 was found to be the optimal vector for in utero cochlear gene transfer. It efficiently transduced progenitors giving rise to both inner and outer hair cells and supporting cells and had no adverse effect on cochlear cell differentiation. Further, it had no pathological effect on differentiated hair cells or the integrity of the auditory nerve or brain-stem nuclei as measured by auditory brain-stem response testing. AAV2/1 promises to be useful in further studies evaluating differentiation pathways of cochlear cells in health and disease and for developing gene-based therapies for congenital and acquired forms of peripheral hearing loss.

488. Adeno-Associated Viral Serotype 2/1 Is a Highly Efficient Vector for In Utero Gene Transfer to Hair Cell Precursors

Gene transfer during gestational development represents a promising gene therapy strategy for correction of congenital developmental anomalies. Congenital hearing deficits may one day be treated in this manner as gene transfer to precursor hair cells may prove to be a highly efficient means of generating transgene expression in a high percentage of mature hair cells. Through exo-utero and transuterine microsurgical approaches, we tested delivery of lentivirus and an array of recombinant adeno-associated viral serotypes (rAAV) expressing enhanced green fluorescent protein (eGFP) to the E11-12.5 developing mouse otocyst. We examined the ability of these viral vectors to successfully infect hair cell precursors and to express eGFP by post-natal day 0 (P0). We noted successful infection of hair cells and eGFP expression from lentivirus, AAV 2/1 and AAV 2/8. We then studied the longer term expression of these viral vectors and found AAV 2/1 to be a highly efficient vector for transduction of both inner and outer hair cells. The hearing thresholds of mice injected with these viral vectors were tested by ABR response and with the exception of the lentivirus injected group, were found to be unchanged from uninjected controls. Thus, in utero microinjection of rAAV, especially AAV 2/1, into the developing mouse otocyst represents an exciting and highly efficient new approach to gene delivery to murine hair cells.

Present Otologic Status of Subjects Implanted with Auditory Prostheses

Thirteen persons who had functioning cochlear prostheses underwent medical evaluation. The nine males and four females ranged in age from 26 to 67 years at the time of the evaluation. Their mean age was 48.1 years. The etiology of deafness had been determined prior to implant surgical procedures in 6 of the 13 subjects. Of the remaining seven subjects, four had acquired hearing losses of unknown causes and three had congenital hearing deficits of unknown cause. All subjects participating in the study gave histories or findings compatible with severe loss or absence of vestibular function. All subjects had well-healed postauricular scars. The implant hardware was physically well-tolerated by the subjects and did not disrupt middle ear function. The implanted subcutaneous coil appeared to be well-tolerated and firmly anchored to the skull in every patient. There was no evidence of irritation to the skin or surrounding tissue. The skin surrounding a percutaneous plus which had been in place for six years in one subject showed no evidence of rejection. However, one subject who had electrode leads implanted beneath external auditory canal skin exhibited chronic external otitis. With this exception, the implant devices were clinically well-tolerated.