Clinical and Genetic Analysis of Enlarged Vestibular Aqueducts

NCT00023036 | Completed

• 2 other identifiers: 01022801-DC-0228
• Study Type: observational
• Target: 324
• Locations: 1 country
• Sites: 1

Brief Summary

This study will try to identify and understand the genetic factors that lead to an inner ear malformation called "enlarged vestibular aqueducts", that can be associated with hearing loss. Patients with sensorineural hearing loss with or without inner ear malformations and their parents and siblings may be eligible for this study. Participants and their immediate family members, may undergo some or all of the following tests and procedures:

• Medical and family history, including questions about hearing, balance and other ear-related issues, and review of medical records.
• Routine physical examination.
• Blood draw or buccal swab (brushing inside the cheek to collect cells) - Tissue is collected for DNA analysis to look for changes in genes that may be related to hearing loss.
• Hearing tests - The subject listens for tones emitted through a small earphone.
• Balance test (VEMP) to see if balance functions of the inner ear are associated with the hearing loss Electrodes will be placed behind your ear and at the base of your neck. From a reclining position, you will be asked to raise your head while clicking sounds are played into your ears. - Ultrasound tests - An inner ear malformation called EVA (enlargement of the vestibular aqueduct) indicates that a genetic disorder called Pendred syndrome may be the cause. Because thyroid abnormalities are also associated with Pendred syndrome, an ultrasound examination of the thyroid gland may be done.
• Computed tomography (CT) and magnetic resonance imaging (MRI) scans - These tests show the structure of the inner ear. For CT, the subject lies still for a short time while X-ray images are obtained. For MRI, the patient lies on a stretcher that is moved into a cylindrical machine with a strong magnetic field. The magnetic field and radio waves produce images of the inner ear. The radio waves cause loud thumping noises that can be muffled by the use of earplugs.

Conditions

Sensorineural Hearing Loss; Cytomegalovirus Infection

Keywords

Genetics; Deafness; Genetic Markers; Genetic Analysis; GENETIC LINKAGE; Natural History; Hearing Impairment; Nonsyndromic Hereditary Hearing Impairment; SNHL; Inner Ear; Enlarged Vestibular Aqueducts; EVA

Outcome Measures

Primary Outcomes (1)

• By using genetic linkage, identify and map possible additional mutant alleles of SLC26A4 or other genes causing nonsyndromic EVA in patients with one or no detectable mutant allele of SLC26A4

  Identify genes other than SLC26A4 that cause EVA.

  ongoing

Study Arms (4)

1

Patients with known or suspected nonsyndromic SNHL associated with EVA

2

Patients with nonsyndromic EVA

3

unaffected siblings and parents of affected family members

4

Other unaffected relatives; included if there is more than one sibship with affected family

Eligibility Criteria

• Age: Up to 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Affected and non-affected family members and affected single sporadic subjects with sensorineural hearing loss and enlarged vestibular aqueducts.

You may qualify if:

• Subjects must have or be a family member of a participant with known or non-syndromic SNHL associated with EVA or have evidence of other findings that suggest that EVA might be part of a novel phenotype
• There must be at least two participating affected family members with one exception: if there is only one participating affected family member, there must be genetic test results identifying only one pathogenic mutant allele of SLC26A4
• Adults must be able to provide informed consent
• Minors must have a parent or guardian able to provide consent
• Age between 0-99.

You may not qualify if:

• Subjects with known exposure to physical or chemical teratogens in utero that could account for their inner ear malformations such as thalidomide or radiation
• Any hearing loss that is associated with symptoms which meet the criteria of already known syndromes, such as, branchio-oto-renal (BOR) syndrome, which comprises system malformations and branchial cleft abnormalities and is caused by heterozygous mutations in the EYA1 gene.
• Previous genetic testing identifying two pathogenic mutant alleles of SLC26A4.
• Prospective study subjects who are cognitively impaired and lack consent capacity, will not be enrolled.

Sponsors & Collaborators

• National Institute on Deafness and Other Communication Disorders (NIDCD): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Bauman NM, Kirby-Keyser LJ, Dolan KD, Wexler D, Gantz BJ, McCabe BF, Bale JF Jr. Mondini dysplasia and congenital cytomegalovirus infection. J Pediatr. 1994 Jan;124(1):71-8. doi: 10.1016/s0022-3476(94)70256-x.

  PMID: 8283378 BACKGROUND

• Dahle AJ, Fowler KB, Wright JD, Boppana SB, Britt WJ, Pass RF. Longitudinal investigation of hearing disorders in children with congenital cytomegalovirus. J Am Acad Audiol. 2000 May;11(5):283-90.

  PMID: 10821506 BACKGROUND

• Everett LA, Glaser B, Beck JC, Idol JR, Buchs A, Heyman M, Adawi F, Hazani E, Nassir E, Baxevanis AD, Sheffield VC, Green ED. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet. 1997 Dec;17(4):411-22. doi: 10.1038/ng1297-411.

  PMID: 9398842 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hearing Loss, Sensorineural; Cytomegalovirus Infections; Deafness; Hearing Loss; Nonsyndromic sensorineural hearing loss

Condition Hierarchy (Ancestors)

Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Thomas B Friedman, Ph.D.

  National Institute on Deafness and Other Communication Disorders (NIDCD)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 21, 2001
• First Posted: August 22, 2001
• Study Start: September 4, 2001
• Last Updated: May 1, 2026

Record last verified: 2026-02-02

Locations

US (1)