Pam, a pediatric audiologist at a small hospital in California, has just confirmed severe to profound sensorineural hearing loss in 3-month-old Santiago, who failed his newborn hearing screening. Now she brings in his parents to discuss amplification and the importance of pinpointing the cause of Santiago's hearing loss.
Pam asks Santiago's parents about their family history and learns that Santiago's two older siblings are healthy and have normal hearing. No other family members have hearing loss. Santiago's parents are concerned about the cause of his hearing loss, and cannot believe this has happened to them because they have no other family members with hearing loss. Pam explains some basics about causes of hearing loss. They are surprised to learn that more than half of severe to profound hearing loss occurring at birth or in the first few years of life has a genetic cause. Pam also explains that hearing loss can be hereditary—that is, genetic—even when the child is the only person in the family who has a hearing loss.
Santiago's parents want to learn more, so Pam encourages them to participate in genetic evaluation to help determine the best treatment options. As part of the referral to genetic evaluation and counseling services, she provides a parent brochure on genetics and hearing loss. Armed with this information—and following a discussion with Pam about the benefits—the family feels empowered to make a decision about whether to pursue genetic evaluation.
As this vignette demonstrates, audiologists not only serve as referral sources, but they also provide basic information to families to help them become comfortable with the genetic evaluation, counseling, and testing process. An audiologist also can assess how well the family understands the information they may learn through genetic evaluation and testing.
Do the parents clearly understand any diagnosis received? If the information refers to genetics, can they accurately recall what they were told about the inheritance pattern? Do they understand the implications of the diagnosis for other family members, including their own future children and grandchildren?
If the parents seem confused or unclear about any of this information, the audiologist can re-refer to the genetics physician or counselor as necessary.
Genetic factors account for nearly 60% of childhood hearing loss, so the parents of every child with hearing loss should have the option of participating in genetic evaluation and counseling provided by a clinical geneticist—that is, a genetics physician—and a genetics counselor. The genetic evaluation includes the collection of a three-generation family history, medical and birth history, and a physical examination to look for clues of a possible environmental or syndromic cause.
Genetic testing is most efficient and cost-effective when other diagnostic information about the individual—family history, ethnicity, and evidence of syndromic or nonsyndromic hearing loss—guides the testing strategy. Genetic testing is available for several dozen of the hundreds of genes known to cause hearing loss. It is standard practice to offer GJB2/GJB6 (connexin 26/connexin 30) testing for all children who are identified as having nonsyndromic hearing loss, because mutations in this gene are a common cause of hearing loss in many populations. In those individuals for whom GJB2/GJB6 mutations are not the cause of hearing loss, follow-up medical testing/screening—for example, imaging studies of the inner ear or vision screening—and/or other genetic testing may be done, guided by information about the family history, ethnicity, and audiologic characteristics.
If evaluators determine that a child has characteristics of a syndrome—the cause of a third of all genetic hearing loss—the genetic testing strategy is more focused. For example, if Santiago had physical features of Waardenburg syndrome—a pigmentary syndrome that occurs commonly in those with severe to profound congenital hearing loss—genetic testing would focus on a few genes, mutations of which are known to cause Waardenburg syndrome type I or type II.
Many types of genetic testing are based on DNA sequencing, which identifies the order of each of the chemical subunits of DNA in a particular gene or a portion of the gene (Welch, 2006). Sequencing allows the identification of "mutations" or changes in one or more subunits of DNA that may affect the function of the gene and cause hearing loss. However, sequencing more than a few of the hundreds of genes that can cause hearing loss using traditional techniques is very expensive and labor intensive.
In the past few years, new technologies that allow the simultaneous sequencing of dozens of genes have been developed. Known as "next-generation sequencing" or massively parallel sequencing, these technologies are helping to overcome some previous testing limitations.
Several genetic testing laboratories have used these technologies—which focus on sequencing dozens of genes at the same time—to develop tests designed specifically for hereditary deafness. These products are now clinically available and are used with increasing frequency in pediatric and adult patients (Brownstein et al., 2011; Kathiyal et al., 2010; Shearer, Hildebrand, Sloan, & Smith, 2010). As these technologies are perfected and their costs reduced, they will largely replace the sequential sequencing strategies used to test for genetic forms of hearing loss.
Ultimately, clinical geneticists—with a single blood test—will be able make an exact molecular diagnosis in a far greater percentage of patients with hearing loss. Children who have syndromes such as Usher, Pendred, or Jervell and Lange-Nielsen may receive an accurate diagnosis before the onset of symptoms, improving patient care and treatment.
Genetic counseling is an important component of the genetic evaluation process, even when the client doesn't need or want genetic testing. Genetic testing is ideally accompanied by pre- and post-test counseling. The genetics team determines if genetic testing will be beneficial in determining the exact diagnosis, and informs parents about different types and costs of testing available at different laboratories. Pre-test counseling addresses the options, risks, benefits, and limitations of genetic testing.
Any discussion about limitations of testing should emphasize that only a small portion of the genes that cause hearing loss have been identified, and testing is available for only some of those. Even if genetic testing does not identify the involvement of a specific gene, the hearing loss can still be genetic. On the other hand, the identification of the exact cause on the molecular level can provide families with valuable information for treatment and family planning.
Post-test counseling from a qualified geneticist or genetics counselor involves a thorough explanation of test results, along with their implications for the family and future family planning. The counselor helps the family explore what the test results mean, and how the family will use them. The information provided to a family during genetic evaluation and counseling can be difficult to process, both emotionally and intellectually. A skilled geneticist or genetics counselor can convey information in an atmosphere that is supportive of the cultural differences and psychosocial needs of the family.
The audiologist plays an important role in assessing the family's understanding and monitoring their reaction to the information they receive. It's helpful to pose specific questions to the family: What did you learn about the cause of the hearing loss? What does this mean for your other children or other relatives? How are you coping with this diagnosis? The audiologist might also recommend the family return to the genetics counselor if there is confusion, frustration with indefinite results, unresolved feelings of guilt or anxiety, or other issues (Pandya & Arnos, 2006).
Santiago and his parents return to see Pam in the audiology clinic after Santiago's genetics evaluation is complete. They are relieved that Santiago's physical examination gave no indication of a syndromic cause of hearing loss. The family chose the option of genetic testing through a laboratory that screens for multiple genes for deafness with one test. Santiago's results were negative—he did not have a mutation in any of the genes included in the test.
Pam talks to the family about their reaction to the information they have learned so far. The parents are comfortable with this "negative" result. They clearly understand that it is possible Santiago has a form of genetic hearing loss for which a test is not yet available, or that he may have an environmental cause of hearing loss that could not be identified. Santiago's parents clearly explain to Pam their awareness that any future children they have may also have a hearing loss.
When Santiago is older—and certainly by the time he is planning his own family—they understand that a re-evaluation may bring new answers. Pam reassures the parents that they are always welcome to bring her any new questions, and that she is prepared and willing to help them re-contact the genetics counselor if necessary. For this family, the audiologist's interest and involvement has helped them better understand the cause of their child's hearing loss.