Natural History and Genetic Studies of Usher Syndrome

This study will explore clinical and genetic aspects of Usher syndrome, an inherited disease
causing deafness or impaired hearing, visual problems, and, in some cases, unsteadiness or
balance problems. Patients with type 1 Usher syndrome usually are deaf from birth and have
speech and balance problems. Patients with type 2 disease generally are hearing impaired but
have no balance problems. Patients with type 3 disease have progressive hearing loss and
balance problems. All patients develop retinitis pigmentosa, an eye disease that causes poor
night vision and eventually, blindness.

Patients of any age with Usher syndrome may be eligible for this study. Patients who have had
eye and hearing evaluations are asked to send their medical records to the research team at
the National Eye Institute (NEI) for review. They are also asked to have a blood sample drawn
by a medical professional and sent to NEI for genetic analysis. Finally, they are interviewed
about their family histories, particularly about other relative with eye disease. Patients
who have not been evaluated previously have the following tests and procedures at NIH:

- Family medical history, especially regarding eye disease. A family tree is drawn.

- Blood draw for genetic studies of Usher syndrome.

- Eye examination to assess visual acuity and eye pressure, and to examine pupils, lens,
retina, and eye movements.

- Electroretinogram (ERG) to test the function of visual cells. Wearing eye patches, the
patient sits in a dark room for 30 minutes. Electrodes are taped to the forehead and the
eye patches are removed. The surface of the eye is numbed with eye drops and contact
lenses are placed on the eyes. The patient looks inside a hollow, dark globe and sees a
series of light flashes. Then a light is turned on inside the globe and more flashes
appear. The contact lenses sense small electrical signals generated by the retina when
the light flashes.

- Fluorescein angiography to evaluate the eye's blood vessels. A yellow dye is injected
into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina
are taken using a camera that flashes a blue light into the eye. The pictures show if
any dye has leaked from the vessels into the retina, indicating possible blood vessel
abnormality.

- Hearing tests to help determine the patient's type of Usher syndrome. Tests to evaluate
hearing include examination of both ears with an otoscope, evaluation of the middle ear
and inner ear, and hearing tests using earphones that deliver tones and words the
subject listens and responds to.

- Vestibular testing for balance function. Balance testing involves three procedures:

Videonystagmography: This test records eye movements with little cameras. First the patient
follows the movements of some small lights. Next, while wearing goggles, the patient lies on
an exam table and turns to the right and left. Lastly, a soft stream of air is blown into the
patient's ears four times, once in each ear with cool air and once in each ear with warm air.

Rotary chair test: With electrodes placed on the forehead, the patient sits in a rotary chair
in a dark room. Several red lights appear on the wall of the room and the patient follows the
lights as they move back and forth. Then the chair turns at several speeds, all slower than a
merry-go-round.

Vestibular evoked potential: Electrodes are placed behind the patient's ear and at the base
of the neck. Seated in a reclining chair and wearing earphones, the patient hears a brief
series of loud clicking sounds. When the sounds are on, the patient is asked to lift his or
her head up a few inches from the chair. The electrodes record information from the muscles
in the neck as the sounds enter the ear.