This study will try to identify and understand the genetic factors that can lead to inner ear malformations that cause 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 tests to see if balance functions of the inner ear are associated with the hearing loss - In one test the subject wears goggles and watches moving lights while cold or warm air is blown into the ears. A second test involves sitting in a spinning chair in a quiet, dark room.

- Photograph - A photograph may be taken as a record of eye shape and color, distance between the eyes, and hair color.

- 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. Also, ultrasound examination of the kidneys can detect malformations that may be inherited along with inner ear malformations associated with another genetic disorder called branchio-oto-renal (BOR) syndrome.

- 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.

- Perchlorate discharge test - Patients suspected of having Pendred syndrome will have this diagnostic test, which takes about 5 hours to complete. The patient swallows a capsule containing radioactive iodine, followed about 90 minutes later by three or four capsules of perchlorate, a type of salt. A monitor is then held over the neck and over the thigh for a few minutes once every 30 minutes.

Condition
Sensorineural Hearing Loss Cytomegalovirus Infection

Nonsyndromic hereditary hearing impairment is a genetically heterogeneous disorder that can be caused by mutations in any one of at least 60 different genes. Enlargement of the vestibular aqueduct (EVA) is a radiologic finding known to be associated with mutations in one of these genes, the Pendred syndrome gene (PDS). EVA may thus serve as a clinically useful marker to facilitate the diagnosis of hearing impairment. Recent data from our laboratory and others indicates that only a subset of individuals with EVA have PDS mutations, and therefore some EVA cases are likely to be caused by other genes, nongenetic factors, or a combination of these etiologies. One of these etiologies includes infectious teratogens such as cytomegalovirus (CMV), which is known to cause inner ear malformations such as EVA in children with severe congenital multisystemic CMV infections. Most congenital CMV infections are much less severe and are asymptomatic. Sensorineural hearing loss is a frequent sequel of congenital CMV infections, including asymptomatic CMV infections, and the resulting hearing phenotype is very similar to that associated with EVA. The temporal bone radiologic phenotype associated with asymptomatic CMV infection is unknown. Individuals with hearing impairment and EVA will be enrolled in this study in order to: (1) Prospectively determine the prevalence of PDS mutation in EVA patients; and (2) correlate phenotypic features with PDS genotype status. Furthermore, in order to identify a potential role of CMV in causing EVA, individuals with congenital CMV infection and hearing loss will also be enrolled in order to: (3) identify and characterize inner ear malformations in children with hearing loss caused by congenital CMV infection; and (4) determine if PDS mutation carrier status is a risk factor for hearing loss and/or inner ear malformations (e.g., EVA) in children with congenital CMV infection. Siblings and parents may also be enrolled in order to define inheritance and to perform molecular genetic analyses.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Patients with known or suspected nonsyndromic SNHL associated with inner ear malformations will be recruited.
Both sporadic and familial cases will be included.
Siblings and biological parents of study subjects with SNHL and inner ear malformations will also be eligible in order to identify subclinical phenotypes, determine the mode of inheritance, and facilitate the molecular genetic analyses.
Referral will be accepted from otolaryngologists, audiologists, medical geneticists, genetic counselors, other health care professional, as well as self-referrals from potiential study subjects and their family members. Given the rarity of these disorders, referrals will be accepted worldwide and subjects from all ethnic backgrounds will be recruited.
EXCLUSION CRITERIA:
Patients known to be exposed to physical or chemical teratogens in utero may be excluded because their inner ear malformations could be due to these nongenetic etiologies (e.g., thalidomide, radiation, etc.).
Hearing loss that is associated with previously described syndromes such as bronchio-oto-renal (BOR) syndrome.

Maryland
      National Institute on Deafness and Other Communication Disorders (NIDCD), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  010228; 01-DC-0228
Record last reviewed:  August 2, 2004
Last Updated:  August 2, 2004
Record first received:  August 21, 2001
ClinicalTrials.gov Identifier:  NCT00023036
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-11-08