The purpose of this investigation is to gain additional knowledge about what causes type 1
and type 2 Usher syndrome-inherited diseases that can cause balance problems and impaired
hearing and vision-and to develop better diagnostic tests. 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. All patients
develop eye problems that cause difficulty seeing in the dark.
The development of newer and more sophisticated diagnostic tests may detect subtle
differences in signs and symptoms that allow more accurate distinction between the two types
of Usher syndrome. This study will use these tests to classify these syndromes and
eventually identify the genes responsible for them.
Study participants will have a medical and family history taken and a family tree
constructed. They will undergo a thorough eye examination, including special tests of color
vision, field of vision, and ability to see in the dark. An electroretinogram will be done
to measure the function of cells in the retina, and a procedure called fluorescein
angiography will be done to look at and photograph the blood vessels in the retina. Special
hearing and balance tests will also done. Hearing tests include physical examination of the
ears and wearing earphones while listening to tones. Balance and coordination tests require
tasks such as walking in a straight line and standing in the dark with eyes closed. A
caloric stimulation test will also be done, in which a small amount of water is irrigated
into the ear canal. For gene studies, blood samples will be collected from patients and all
available family members.
The Usher Syndromes (USH), characterized by autosomal recessive inheritance, are
genotypically distinct diseases which share specific phenotypic characteristics. Affected
individuals have congenital neurosensory hearing impairment of variable severity and a
progressive pigmentary retinal degeneration commonly referred to as retinitis pigmentosa.
Interfamilial differences in USH patients are greater than intrafamilial differences and
investigators have proposed at least two distinct phenotype types; Usher Syndrome type 1
(USH 1) and Usher Syndrome type 2 (USH 2) (Fishman 1983). Patients with USH 1 are
profoundly deaf from birth, have unintelligible speech and absent vestibular function.
Nightblindness is apparent in the 1st or 2nd decade accompanied by an extinguished
electroretinogram (ERG) and profound loss of visual field. Patients with USH 2 can have
moderate to severe hearing loss and normal vestibular function. Nightblindness occurs in
the 2nd or 3rd decade, there is variable field loss and variable response by the ERG
Heterogeneity has been verified by linkage studies and at least three USH 1 loci and two USH
2 loci are known (Kimberling et al 1990; Lewis et al 1990; Kaplan et al 1992; Smith et al
With increasingly sophisticated clinical testing, subtle differences may permit a more
accurate distinction between the two USH phenotypes. The purpose of this study is to
classify as accurately as possible these patients' clinical features by careful audiologic,
vestibular, psychophysical and electrodiagnostic testing and correlate these with the
genetic mutations identified through linkage studies and eventually to the genes (genetic
mutations) as they become identified.
- Patients must have documentation of neurosensory hearing loss and retinitis
pigmentosa and fulfill the clinical characteristics (Table) as accepted for USH 1 and
- The minimal test battery will identify all patients with USH 1 and USH 2 as well as
- Candidates will be recruited from lists of patients willing to participate in
research studies compiled by the R.P. Foundation, and by referral from their private
- On occasion additional family members will be studied after an initial individual is
ascertained as above.
- No patients with intrauterine and childhood infections, and intrauterine and birth
complications can result in trauma to both the auditory or visual system and a
positive history for these conditions will necessitate exclusion from the study.