Clinical and Ethical Implications of Deafness Research
Nance, Walter, Dodson, Kelley, Volta Voices
In the past two decades, three important advances - the development of advanced hearing technology, the initiation of newborn hearing screening and the successful sequencing of the human genome - have had a dramatic impact on our knowledge of hearing loss.
Now, more than ever, identifying what causes deafness can be just as important as detecting hearing loss, an idea that has helped genetic testing earn recognition as an important complement to newborn hearing screening. However, continued collaboration between health care professionals and scientists is needed to further expand the rapidly growing body of knowledge.
Incidence of Deafness
Clinically significant congenital hearing loss, generally defined as a sensorineural loss of 35 dB or more in either ear, occurs about every 1.86 per 1,000 births in the United States. This number continues to rise throughout life, affecting 3.5 per 1,000 children during adolescence and 40 to 50 percent of adults by age 70.
Although genes related to hearing loss are present at the time of conception, all forms of genetic deafness may not be expressed at birth. For example, at least one in five cases of prelinguistic hearing loss is not expressed at birth, making it undetectable by newborn hearing screening methods that do not include molecular and genetic testing.
Common Genetic Causes of Deafness
In the United States, genetic factors account for nearly 70 percent of infants with congenital hearing loss and slightly more than half of children who develop hearing loss by age 4. Yet, most newborn hearing screening programs do not include supplementary genetic and molecular testing as part of standard care (Morton and Nance, 2006).
Molecular tests are available to detect three of the most common forms of genetic deafness: Connexin, Pendred syndrome and mt A1555G substitution. If testing for these three genes and the nongenetic cytomegalovirus infection were added to screening protocols for all newborns, at least 50 percent of infants who develop late-onset prelinguistic hearing loss could be identified at birth (Morton and Nance, 2006).
Mutations involving the connexin 26 gene, also known as DFNB1 and GJB2, account for 30 to 40 percent of all genetic deafness in many, but not all, populations. DFNB1 refers to the chromosomal region where the gene was initially localized or "mapped" before its identity was discovered. This region carries several genes, including two neighboring genes that can cause deafness and code for the proteins GJB2 and GJB6. These proteins form the subunits of intracellular gap junction channels, pathways that allow small molecules including potassium ions, to move between adjacent cells. In fact, the inner ear recycles potassium through these channels, a process that plays a critical role in the perception of sound. Auditory signals that emanate from inner ear hair cells depend on the recycling of potassium, which is thought to be disrupted in the presence of connexin mutations.
In most cases, connexin 26-related deafness is expressed at birth and the hearing loss, but not the cause, can be detected through newborn hearing screening. However, in up to 4 percent of cases, the deafness is not expressed until later in infancy (Norris et al., 2006). These infants would also benefit from early detection and intervention but cannot be identified at birth without molecular testing.
Pendred syndrome is a recessive trait accounting for up to 5-10 percent of genetic deafness. It is associated with a specific type of goiter, or enlargement of the thyroid gland, that may not become apparent until the second decade of life. More recently, inner ear abnormalities including Mondini malformation and enlargement of the vestibular aqueduct (EVA) have also been documented in Pendred syndrome, as well as in cases of hearing loss that are not associated with goiter. …