Usher syndrome is a genetic condition that in most cases is characterized by congenital hearing loss, followed by progressive vision loss that begins a decade or so later.
Usher syndrome is the most common single cause of combined deafness and blindness and affects at least 20,000 people in the US alone. Affected individuals experience communication barriers, educational difficulties, stress, social isolation, depression, fear of blindness and a staggering unemployment rate: greater than 80%. Most affected individuals rely upon Social Security Disability and Medicaid.
16,000 unemployed Americans cost the US government at least $160 million per year. Of course, the human costs and the costs of lost productivity associated with of Usher syndrome are many-fold greater than this.
Usher syndrome can be divided clinically into three types depending on the onset and severity of the hearing loss, and whether or not an individual’s sense of balance is affected.
Type I (about 35% of patients in the US) is associated with profound hearing loss at birth and abnormal balance. These children often learn to walk many months later than their peers. Many of these children would not develop normal speech without receiving a cochlear implant in early childhood.
Type II (about 65% of patients in the US) is associated with stable, milder hearing loss that is present at birth and normal balance. These children often develop near normal speech using conventional hearing aids.
Type III (less than 5% of patients in the US) is characterized by progressive hearing loss that begins after the development of speech and variable balance issues.
All three types of Usher syndrome are associated with a progressive retinal condition known as retinitis pigmentosa, which begins with abnormal night vision and peripheral vision and progresses over years to a small “tunnel” of vision, and in some cases, even complete loss of vision. A comprehensive discussion of Usher Syndrome symptoms and progression can be found at the Usher Syndrome Coalition (Type 1; Type 2; Type 3).
Usher syndrome is inherited in an autosomal recessive fashion, meaning that most patients inherited one abnormal copy of an Usher-causing gene from each parent. Males and females are equally likely to be affected. Over 95% of all currently known Usher-causing mutations lie in one of eight genes. The two most common Usher-causing genes are USH2A (59% of molecularly confirmed cases) and MYO7A (24% of molecularly confirmed Usher cases).
Genetic tests for Usher syndrome vary widely in cost and complexity. The most sensitive tests can now find the disease-causing mutations in more than 75% of Usher patients. The least expensive approach is to use a “tiered” test in which the more common mutations are looked for first. Such an approach can achieve a sensitivity of nearly 50% for less than $575. Further cost reductions (less than $400 per patient) can be achieved if large numbers of patients are screened in groups (for example in a research study or a state program designed to follow-up abnormal newborn hearing tests with molecular screening).
Treatments for Usher syndrome can be divided into family planning, cochlear implants, hearing aids, gene therapy, stem cell therapy, and assistive devices. Newborn hearing testing coupled with genetic testing makes it possible to diagnose Usher syndrome much earlier than ever before. As a result, many of these treatment modalities are now more effective than they were in the past.
Family Planning – Couples who are carriers of the same Usher syndrome gene are at 25% risk (with each pregnancy) of having a child with Usher syndrome. Early diagnosis of the first child with associated genetic counseling makes it possible for a family to avoid having another affected child by various means ranging from adoption to pre-implantation genetic testing. The latter method involves in vitro fertilization and allows couples to have additional biological children while dramatically reducing the risk of having a second affected child.
Hearing Aids and Cochlear Implants – Conventional hearing aids, provided at a very young age to a child with type 2 Usher syndrome, can dramatically improve the child’s speech and educational development. Cochlear implants are surgically implanted devices that stimulate the nerves of the inner ear with electrical signals derived from a microphone. These devices often allow children with profound hearing loss (as seen with type 1 Usher syndrome) to develop quite normal speech.
Gene Therapy – Usher patients with early stage disease may benefit from viral-mediated replacement of the dysfunctional gene. Such a treatment has already been devised for USH1B (MYO7A) and is now in human clinical trials. USH2A is a much larger gene and effective treatment for this Usher subtype will require larger vectors (such as helper-dependent adenovirus) or genome editing strategies such as CRISPR-Cas9. Rarer forms of Usher Syndrome (e.g., USH1F and USH1C) may eventually benefit from non-profit, philanthropically-funded development of gene therapy reagents.
Stem Cell Therapy – Usher patients who have already lost the majority of their photoreceptors require some means of stimulating the bipolar cells and ganglion cells of the inner retina in response to light. A breakthrough in stem cell biology in 2007 made it possible to create embryonic-like stem cells (known as induced pluripotent stem cells) from a small biopsy taken from a patient’s skin. Photoreceptor-precursor cells made from such cells have been successfully transplanted into animals and it is hoped that such a strategy will eventually result in the restoration of vision for patients with late stage retinitis pigmentosa.
Assistive Devices -- The functional abilities of individuals with vision loss from Usher’s Syndrome can be enhanced using a variety of adaptive devices prescribed based on the individual’s needs for distance, intermediate and near vision enhancement. Adaptive devices include reading spectacles, hand and stand magnifiers, hand held and spectacle mounted telescopes, absorptive lenses, electronic magnification devices, tablets, and computer adaptations including voice recognition and text to speech software.