NIDCD Recent Research Hereditary Deafness

What Is Hereditary Deafness?

Hereditary deafness is hearing loss that is inherited or passed down from parents to their children. This type of hearing loss may be inherited from one or both parents who may or may not have a loss of hearing themselves.

Hereditary material or genes are located on chromosomes which are found in each cell of the body. Genes provide instructions for specific traits or characteristics such as hair color or blood type. Defective genes can also pass along traits such as hearing loss or speech and language disorders.

The hereditary hearing loss that results from defective genes may be syndromic or nonsyndromic, dominant or recessive. Syndromic hearing loss is associated with specific traits additional to hearing impairment. For example, hearing, balance and visual problems occur in Usher syndrome. Nonsyndromic hearing impairment has hearing loss as its only characteristic. Dominant transmission of deafness requires only one faulty gene, from either the mother or father to cause the hearing loss, whereas recessive transmission of deafness requires a faulty gene from both the mother and father.

Of the more than 4,000 infants born deaf each year, more than half have a hereditary disorder. However, not all hereditary hearing loss is present at birth. Some infants may inherit the tendency to acquire hearing loss later in life.

Scientists supported by the National Institute on Deafness and Other Communication Disorders (NIDCD) are on the forefront of research on the molecular bases of hearing and deafness, continuing to explore the genetics of hearing loss in a variety of disorders, including Waardenburg syndrome, Usher syndrome, nonsyndromic hereditary deafness, otosclerosis, adult-onset hearing loss and presbycusis and the hereditary predisposition to noise-induced hearing loss and otitis media. This research should lead to a better understanding of how hearing impairment or deafness is transmitted from parent to child, making it possible to identify and characterize the genes in which changes or mutations cause hearing impairment. Through these efforts it may be possible to discover how genes work, what proteins they manufacture and the role they play in the development and maintenance of normal hearing. These discoveries should lead to early diagnosis, prevention and treatment, such as gene transfer therapy.

RESEARCH ON HEREDITARY DEAFNESS SYNDROMIC HEARING IMPAIRMENT

There are more than 200 forms of syndromic hereditary hearing impairment. NIDCD-supported scientists have been able to map or locate the abnormal genes on their chromosomes for three of these hereditary syndromic forms of hearing loss: Waardenburg syndrome (WS) type 1 and Usher syndrome types 1 and 2. WS type 1, which accounts for two to three percent of all cases of congenital deafness, has been mapped to a narrow band on the long arm of chromosome 2. Usher syndrome type 2 has been mapped to chromosome 1 and type 1 has been mapped to chromosome 11. These two types account for approximately ten percent of all cases of congenital deafness.

Both Usher syndrome types 1 and 2 are recessive disorders which cause congenital hearing loss and late-onset blindness due to retinitis pigmentosa. Usher syndrome type 1 is characterized by severe hearing loss, complete loss of balance and blindness. Usher syndrome type 2 is characterized by moderate hearing loss, normal balance function and blindness. More than half of the approximately 16,000 deaf and blind people in the United States are believed to have Usher syndrome.

WS types 1 and 2 are dominant disorders which are often characterized by hearing impairment and changes in skin and hair pigmentation. Hearing impairment is present in approximately 20 percent of those with WS type 1. In addition, individuals with WS type 1 have an unusually wide space between the inner corners of their eyes. In contrast, approximately 50 percent of individuals with WS type 2 have hearing impairment but they do not have the wide spacing between the inner corners of their eyes.

To accelerate research on WS, an international consortium was formed by the NIDCD in September 1990. The consortium consists of the following six research teams: Boston University Medical School Center for Human Genetics, Boston Massachusetts; Michigan State University Department of Zoology, East Lansing, Michigan; Laboratory of Molecular Biology, NIH-NIDCD, Bethesda, Maryland; Department of Manchester, United Kingdom; Molecular Genetics Laboratory, Virginia Commonwealth University, Richmond, Virginia; and Department of Human Genetics, University of Cape Town Medical School, Cape Town, South Africa.

One team from the consortium recently studied 60 members from six generations of a Brazilian family, 26 of whom were diagnosed with WS type 1. This team discovered that each affected family member had a defect in the gene called PAX 3 on chromosome 2. This defect was due to one amino acid substitution in the gene that was not found in 17 other WS type 1 families unrelated to the Brazilian family, indicating that other mutations may cause the syndrome in other families. Seventy-eight percent of members of this Brazilian family had noticeable hearing loss which is well above the 20 percent found in most WS type 1 cases placing additional importance on the significance of this gene in the development of hearing loss in WS.

A group of scientists has discovered a defective gene in disordered mice referred to as Pax-3 (lower case to distinguish it from the human symbol PAX 3). These mice have hearing loss, pigmentary disturbances and facial changes. The Pax-3 gene, which regulates early development of the mice in the womb, is comparable to the PAX 3 gene found on chromosome 2 in humans. Another team from mutation in the PAX 3 gene in several families with WS type 1.

Non Syndromic Recessive Hearing Impairment

Approximately 80 percent of the nonsyndromic hereditary hearing disorders are recessive. Another international collaboration will provide NIDCD scientists with a rare opportunity to study nonsyndromic recessive hearing impairment in a large segment of the population in southern India where scientists report that 40 to 50 percent of the children in schools for the deaf have this type of hearing impairment. This type of hearing loss has been difficult to study in the United States because of the difficulty in making a definitive diagnosis.

Non Syndromic Dominant Hearing Impairment

A team of NIDCD-supported scientists has located the gene responsible for a nonsyndromic dominant form of hearing impairment in a large family from Costa Rica who develop hearing impairment In late childhood. Hearing loss for the affected members of this family becomes severe between 30 and 40 years of age. These scientists were able to analyze the genetic material of 86 descendents of Felix Monge, an 18th century ancestor who had a hearing loss similar to his 20th century descendents. The gene is located on a specific portion of chromosome 5. Since hearing loss in this family begins later in childhood, rather than at birth, it is possible that this gene is responsible for the maintenance of auditory hair cells during early life.

About The NIDCD

The NIDCD is one of the institutes of the National Institutes of Health (NIH). The NIDCD conducts and supports biomedical and behavioral research and research training on normal and disordered mechanisms of hearing, balance, smell, taste, voice, speech and language.

About The Recent Research Series

This series is intended to inform health professionals, patients, and the public about progress in understanding the normal and disordered processes of human communication through recent advances made by NIDCD supported scientists in each of the Institute's seven program areas of hearing, balance, smell, taste, voice, speech and language.

For additional information on hereditary deafness, write to:

National Institute on Deafness and
Other Communication Disorders
NIDCD Clearinghouse
PO Box 37777
Washington, DC 20013-7777

August 1992

National Institute On Deafness And Other Communication Disorders