Background: The Usher syndromes are a group of clinically variable and genetically heterogeneous autosomal recessive syndromes. On the basis of clinical findings, at least three types exist. Patients with Usher type I are born deaf, in the abscence of cochlear implant do not develop intelligible speech, have vestibular problems, and are thought to perceive night blindness in early childhood. Patients with Usher type II are born with a hearing deficit but are able to develop intelligible speech, do not have balance problems; night vision problems, and visual field changes are noted later. Patients with Usher type III are born with relatively good hearing that deteriorates over a decade or more; they can have progressive balance problems and they report night blindness in childhood or teens. Seven genes have been mapped so far for Usher type I while five of these genes have been identified. For Usher type II, three genes have been mapped and two of these have been identified while there is one cloned gene for Usher type III.

It is apparent that there is quite a lot of information still unknown regarding the genetic nature of this syndrome. The clinical picture of the three different types of Usher syndrome has also not been well studied up to this point and cross sectional studies seem to be the only source of the information available so far, regarding the natural history of the disease.

Aims: The aim of this protocol is two-fold:

1) To better study the natural history of the disease

2) To make specific genotype-phenotype correlations.

Methods: Usher patients who want to participate will provide a copy of their medical records if available. The records will be reviewed by one of the investigators. Patients will have one of three options:

1) If their previous audiologic and ophthalmologic evaluations are complete, an examination at NIH is not necessary. After signing the informed consent the patients will be asked to answer a questionairre and to provide a blood sample. Their clinical data will be entered in an Usher database which will be created by the primary investigator and her collaborators. Only patients with complete ophthalmic and auditory evaluations will have this option.

2) If there is no previous complete ophthalmologic and audiologic evaluation, patients can come to NIH for a complete ophthalmologic and auditory evaluation after signing an informed consent. They will also provide a blood sample.

3) If a previous evaluation does not exist or is incomplete but the patient is unable to travel to NIH, the patient will be examined by outside clinicians and audiologists and forward records to NIH. After signing the offsite informed consent he/she will answer a questionnaire and provide a blood sample.

Condition
Retinitis Pigmentosa Syndromic Congenital Deafness Usher Syndrome Retinitis Pigmentosa and Deafness Progressive Hearing Loss

Further Study Details: 

Expected Total Enrollment:  200

Background: The Usher syndromes are a group of clinically variable and genetically heterogeneous autosomal recessive syndromes. On the basis of clinical findings, at least three types exist. Patients with Usher type I are born deaf, in the abscence of cochlear implant do not develop intelligible speech, have vestibular problems, and are thought to perceive night blindness in early childhood. Patients with Usher type II are born with a hearing deficit but are able to develop intelligible speech, do not have balance problems; night vision problems, and visual field changes are noted later. Patients with Usher type III are born with relatively good hearing that deteriorates over a decade or more; they can have progressive balance problems and they report night blindness in childhood or teens. Seven genes have been mapped so far for Usher type I while five of these genes have been identified. For Usher type II, three genes have been mapped and two of these have been identified while there is one cloned gene for Usher type III.

It is apparent that there is quite a lot of information still unknown regarding the genetic nature of this syndrome. The clinical picture of the three different types of Usher syndrome has also not been well studied up to this point and cross sectional studies seem to be the only source of the information available so far, regarding the natural history of the disease.

Aims: The aim of this protocol is two-fold:

1) To better study the natural history of the disease

2) To make specific genotype-phenotype correlations.

Methods: Usher patients who want to participate will provide a copy of their medical records if available. The records will be reviewed by one of the investigators. Patients will have one of three options:

1) If their previous audiologic and ophthalmologic evaluations are complete, an examination at NIH is not necessary. After signing the informed consent the patients will be asked to answer a questionairre and to provide a blood sample. Their clinical data will be entered in an Usher database which will be created by the primary investigator and her collaborators. Only patients with complete ophthalmic and auditory evaluations will have this option.

2) If there is no previous complete ophthalmologic and audiologic evaluation, patients can come to NIH for a complete ophthalmologic and auditory evaluation after signing an informed consent. They will also provide a blood sample.

3) If a previous evaluation does not exist or is incomplete but the patient is unable to travel to NIH, the patient will be examined by outside clinicians and audiologists and forward records to NIH. After signing the offsite informed consent he/she will answer a questionnaire and provide a blood sample.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
The patients must have documentation of neurosensory hearing loss and retinitis pigmentosa and fulfill the clinical characteristics for USH1, USH2 as defined by the Usher syndrome consortium (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). Patients with documented presence of retinitis pigmentosa, severe to profound hearing loss and absent vestibular responses will be categorized as Usher type I. Patients with documented presence of retinitis pigmentosa, moderate to severe hearing loss and normal vestibular responses will be categorized as Usher type II. Patients with documented presence of retinitis pigmentosa, progressive hearing loss and variable vestibular responses will be categorized as Usher type III.
EXCLUSION CRITERIA:
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. Also patients unwilling to provide a blood sample will be excluded from the study.

Maryland
      National Eye Institute (NEI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  050096; 05-EI-0096
Record last reviewed:  January 24, 2005
Last Updated:  March 29, 2005
Record first received:  March 29, 2005
ClinicalTrials.gov Identifier:  NCT00106743
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08