Guest Blogger Danio, one last time:
The current standard of pediatric care mandating that all newborns undergo hearing screenings has been applied successfully throughout much of the industrialized world. Early identification of hearing impairments gives valuable lead-time to parents and health care providers during which they can plan medical and educational interventions to improve the child’s development, acquisition of language skills, and general quality of life.
Up to 12% of children born with hearing loss have Usher syndrome. However, diagnosing Usher syndrome as distinct from various forms of congenital hearing impairment is often impossible until the onset of retinal degeneration years later. The considerable number and size of the genes involved makes genetic screening impractical with the current methods, unless there is a family or community history that can shorten the list of targets by implicating a particular Usher gene or subtype.
The educational and medical interventions undertaken to improve a deaf or hearing-impaired child’s cognitive and social development can vary extensively, based in part on whether the child in question is expected to lose his or her vision later in life. Thus an earlier diagnosis of Usher syndrome is an immediate and critical research goal. The most imminent hope for such a diagnostic advance lies in gene chip screening. With this technology, the patient’s DNA can be screened against a microarray of human genes known to cause deafness (and/or Usher syndrome) when mutated, and variances in the DNA sequence of any screened gene would be detected and analyzed. One such chip is already available for commercial use, and another appears to be approaching clinical availability. The rapid and affordable analysis these microarrays offer will be of tremendous benefit in the early diagnosis and management of Usher syndrome.
In spite of the considerable amount of information about the pathophysiology of Usher syndrome obtained over the past 10 years, there are, as of yet, no clinically applicable treatments targeting the molecular underpinnings of the disease. Following the diagnosis of hearing impairment in a child, the parents may consider hearing aids or, in cases of profound hearing loss, a cochlear implant. The timing of the installation of these devices is critical, as speech development can be significantly impacted if the child does not begin to hear and reproduce spoken sounds in the first few years of life.
Hearing aids, which amplify sound, are appropriate in cases of moderate hearing loss, where hair cell function is only partially impaired, or where more severe hearing loss is restricted to a certain frequency range. In cases of severe to profound sensorineural deafness, as is the case in type 1 Usher syndrome, traditional hearing aids are ineffective. Cochlear implants are surgically placed devices that can substitute to some degree for defective hair cells. An externally worn processor converts the sound signals it receives into electrical impulses and transmits them to the auditory nerve, via electrodes threaded through the cochlea. Here’s a short video of the placement and mechanism of action of this device:
And here is a link that contains several MP3 files simulating how different types of auditory stimuli–speech and music–might sound through a cochlear implant.
The technology of cochlear implants has steadily improved since their introduction, but the device was not initially met with unmitigated approval. Some members of the deaf community have expressed reservations about cochlear implants, as many believe that deafness, and the subsequent requirement for non-verbal forms of communication, are not defects in need of repair. Although this opposition has lessened somewhat in recent years, parents facing these choices can still sometimes receive conflicting advice about cochlear implants. Clearly, the cultural identify of the deaf community is important to consider, but the knowledge that a hearing impaired child will suffer from progressive vision loss later in life could have a considerable impact on the decision to initiate education in a highly visual form of communication rather than undergo the cochlear implantation. Communication options for Usher patients without cochlear implants include tactile signing, in which ASL signs are executed while touching hands, or traditional ASL conducted in close proximity to the deaf-blind individual, within his or her narrow field of vision, with consideration for contrasting background colors so that the signer’s hands are easily visible against his or her clothing.
There is no treatment for the progressive vision loss in Usher patients. The first sign of a vision problem usually occurs when patients report difficulty seeing at night–a symptom that rod photoreceptor loss in the periphery of the eye is already underway. Further degeneration occurs from the periphery inward, resulting in an increasingly restricted visual field. The rate of retinal cell loss is monitored through regular ophthalmological examinations, and although supplementing the diet with DHA, the well known Omega-3 fatty acid, appears to slow the progression of photoreceptor degeneration in a number of retinal diseases, including Usher syndrome, there are no preventative or curative therapies available.
Currently, the most tractable research toward finding a treatment for the retinal disorder focuses on gene replacement therapy. There have been encouraging results using viral vectors to deliver functional copies of the myo7a gene into retinal cells of myo7a mutant mice, and the use of nanoparticles as a delivery system should provide another fruitful avenue of research. The progressive nature of the retinal degeneration in Usher patients lends itself to the application of such treatments. In principle, an effective therapy initiated early enough could begin rescuing photoreceptors from dysfunction and eventual death prior to the onset significant vision loss, further underscoring the importance of developing methods for early diagnosis.
Discovering more about where and how the Usher proteins function in the eye will be important in determining the optimal target for gene replacement therapy, and animal models of the disease will continue to be indispensible both for basic study of the molecular and cellular physiology of Usher syndrome as well as for the testing of new therapies in preparation for clinical trials.