Study of Usher Syndromes, Type 1 and Type 2
Study of Usher Syndromes, Type 1 and Type 2
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 (Fishman 1983).

 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
 1992a.)

 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.
Inclusion Criteria:

 -  Patients must have documentation of neurosensory hearing loss and retinitis pigmentosa
 and fulfill the clinical characteristics (Table) as accepted for USH 1 and USH 2.

 -  The minimal test battery will identify all patients with USH 1 and USH 2 as well as
 possible subtypes.

 -  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
 physicians.

 -  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.