This study will try to identify and understand the genetic factors that lead to inner ear malformation called "enlarged vestibular aqueducts", that can lead to 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.

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. 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; (2) correlate phenotypic features with PDS genotype status; 3) identify other genetic factors that cause EVA. Siblings and parents may also be enrolled in order to define inheritance and to perform molecular genetic analyses.

• Sensorineural Hearing Loss
• Cytomegalovirus Infection

• 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.
• 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.
• 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.

• INCLUSION CRITERIA:

Patients with known or suspected nonsyndromic SNHL associated with inner ear malformations will be recruited.

Eligibility requires two or more participating affected family members since they are needed for genetic mapping approaches to identify genes in which mutations cause EVA, with the exception of sporadic cases with distinctive phenotypic features that may provide insight in to novel etiologies of EVA.

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.

Referrals will be accepted from otolaryngologists, audiologists, medical geneticists, genetic counselors, other health care professionals, as well as self-referrals from potential 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.