Natural History and Genetic Studies of Usher Syndrome

NCT00106743 | Completed

• 2 other identifiers: 05009605-EI-0096
• Study Type: observational
• Target: 249
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Retinitis Pigmentosa Syndromic; Congenital Deafness; Usher Syndrome; Retinitis Pigmentosa and Deafness; Retinitis Pigmentosa

Keywords

Usher Syndrome; Retinitis Pigmentosa; Congenital Deafness

Outcome Measures

Primary Outcomes (1)

• The primary outcomes of interest are the probands genotype and phenotype.

  1 year

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible participants must:
• have documented neurosensory hearing loss and retinitis pigmentosa and fulfill the clinical characteristics for USH1, USH2 and USH3 as defined by the Usher syndrome consortium. ; OR
• be unaffected family members of a proband with Usher s syndrome, primarily parents and siblings. Family members will be considered unaffected by history if they have had previous normal ophthalmologic and hearing examinations and if they don't have decreased night or peripheral vision.

You may not qualify if:

• Patients will be ineligible if they:
• had an intrauterine infection, perinatal/congenital infections, or intrauterine and birth complications. These conditions can result in damage to both the auditory or visual system.
• have concurrent inherited or acquired conditions that affect the visual and/or auditory system and significantly alter the phenotype.
• Both affected and unaffected individuals will be ineligible if they:
• Are unwilling or unable to provide a blood sample or unable to undergo the study procedures.
• Are younger than 2 years old.

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Queens College of the City University of New York

New York, New York, United States

Location

Related Publications (3)

• Smith RJ, Berlin CI, Hejtmancik JF, Keats BJ, Kimberling WJ, Lewis RA, Moller CG, Pelias MZ, Tranebjaerg L. Clinical diagnosis of the Usher syndromes. Usher Syndrome Consortium. Am J Med Genet. 1994 Mar 1;50(1):32-8. doi: 10.1002/ajmg.1320500107.

  PMID: 8160750 BACKGROUND

• Keats BJ, Corey DP. The usher syndromes. Am J Med Genet. 1999 Sep 24;89(3):158-66.

  PMID: 10704190 BACKGROUND

• Fishman GA, Kumar A, Joseph ME, Torok N, Anderson RJ. Usher's syndrome. Ophthalmic and neuro-otologic findings suggesting genetic heterogeneity. Arch Ophthalmol. 1983 Sep;101(9):1367-74. doi: 10.1001/archopht.1983.01040020369005.

  PMID: 6604514 BACKGROUND

MeSH Terms

Conditions

Usher Syndromes; Retinitis Pigmentosa; Deafness

Condition Hierarchy (Ancestors)

Deaf-Blind Disorders; Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Hearing Loss, Sensorineural; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Blindness; Vision Disorders; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Eye Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Wadih Zein, M.D.

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2005
• First Posted: March 30, 2005
• Study Start: March 21, 2005
• Study Completion: April 30, 2019
• Last Updated: December 12, 2019

Record last verified: 2019-04-30

Locations

US (2)