Some Answers and More Questions
In the last ten years, medical knowledge of genetic information has multiplied exponentially. As is typical of science, testing has outrun our ability to assimilate knowledge into cultural ethics and values. Should we and our children have genetic testing? What is the purpose and what are the outcomes? Scientific and ethical questions describe the voyage of the Human Genome Project, a conglomeration of governmental and private (mostly pharmaceutical) parties who are boldly going where no one has been before.
When we heard our daughter's diagnosis for the first time back in the dark ages of 1998, the prevailing opinion of the time was that "90% of the time, there is no identifiable reason for hearing loss." Now that she has learned to ride a bike, current research indicates that 50% of all childhood deafness is due to heredity or genetics. Even if the family has no relative in their scrapbooks who had a hearing loss.
However, in about 50% of children with severe to profound hearing loss, the cause is identifiable through genetic testing
Why test? One Colorado mother, pondering the sticky issues of genetic testing, jokingly said, "Should I test just so I can point the finger at his family?"
There are more harmonious reasons. Some genetic links to deafness are associated with medical conditions that can benefit from identification and treatment. Some genetic links are associated with progressive hearing loss, and at least one associated condition is life threatening. (see sidebar on Long QT Syndrome). Also, parents might want to know about familial deafness for information about future pregnancies in their own family and extended families. So there are other reasons to test than just to see what might have occurred when her 23 chromosomes met his .
Certainly, there are nongenetic causes to hearing loss. Infection, illness, injury to the mother or baby, and a number of medications can cause hearing loss. 90% of babies who are born with hearing loss are born to hearing parents and often a cause is not identifiable through the medical history. However, in about 50% of children with severe to profound hearing loss, the cause is identifiable through genetic testing.
There are many different types of genetic conditions. They may be "syndromic", involving other medical or physical findings in addition to the hearing loss, or "non-syndromic", meaning that there are no other significant features besides the hearing loss. There are several ways in which hearing loss can be inherited: autosomal dominant, autosomal recessive, X-linked (dominant or recessive), multifactorial, or chromosomal. Genetic hearing loss may be present at birth ("congenital") or it may start later in life. It may be stable or progressive; it may be conductive, sensorineural, or mixed.
Within the 50% of children with a genetically based hearing loss, 30% have hearing loss related to a syndrome, meaning that these babies have other medical problems. More than 400 syndromes have now been identified which can cause hearing loss (see chart below for some examples.)
What Happens in a Genetic Evaluation
Physical Examination: The genetic evaluation is usually done by a team made up of a geneticist, a physician specially trained to recognize signs of genetic conditions, and a counselor who either has a master's degree or Ph.D. in genetics. The medical history (including records from the audiologist and ENT physician) and family history are reviewed and a specialized physical examination is performed. The medical history may identify a medical cause of hearing loss, or it may point out an important symptom of a genetic condition, such as kidney infections or difficulty seeing in the dark. A careful physical examination is done to look for subtle characteristics that can relate to specific genetic conditions. These characteristics by themselves may not be noticeable, and they may appear to be unrelated to hearing loss. For example, small pits in front of the ears could indicate Branchio-oto-renal syndrome, which also involves kidney problems; a white forelock could be part of Waardenburg syndrome; nightblindness or tunnel vision could indicate Usher syndrome, or severe nearsightedness could be a sign of Stickler syndrome.
Family History: The counselor goes over the family history and draws a "family tree", usually covering about three generations. For example, in a consultation for a child, the family history information would cover the child's brothers and sisters, parents and grandparents, and aunts, uncles, and cousins. Any relative with hearing loss is noted, along with any other physical or learning problems they may have had. In addition, there are a number of specific conditions that should be asked about in any relative, whether or not they have hearing loss. This is because syndromes include one or more additional findings in addition to the hearing loss. A person with a syndrome does not necessarily have all of the findings. Thus, the counselor will ask about such things as kidney problems, ear pits, white forelocks, nightblindness, nearsightedness, and so on.
Medical Testing: Typically, both parents and any brothers and sisters are asked to have audiological testing, and medical reports or tests may be needed from other family members as well. In addition, the geneticist may recommend specific medical tests such as ultrasound of the kidneys, an X-ray, or a blood or urine test. An examination by an ophthalmologist is often recommended (if it has not been done already), and an ERG (electroretinogram) may be done to screen for Usher syndrome, which also involves progressive visual problems due to retinitis pigmentosa. An EKG (electrocardiogram) may be done to look for a specific abnormality in the heartbeat that is seen in the Long QT Syndrome (also known as Jervell and Lange-Nielsen syndrome). This would be done especially if there is any history of fainting.
Many of the other recommended tests would have been already done in the process of diagnosing the hearing loss: including a CT scan in order to look at the structure of the middle ear, cochlea, and vestibular system, or an ABR (auditory brainstem response; sometimes called a BER, or brainstem evoked response) to detect a hearing loss in a baby or a person who cannot perform a regular behavioral audiological evaluation. The ABR can also locate where a sensorineural hearing loss has occurred: in the cochlea, the auditory nerve, or in the part of the brain that first receives the sound information. Vestibular testing can show if the balance system of the inner ear has been affected as well. In some genetic forms of hearing loss, the vestibular system may not have developed, and meningitis can also damage the vestibular system. In a very young child, tests for viral infections may show that the child had a congenital infection (that is, an infection before birth) such as CMV (cytomegalovirus) or rubella which could have caused the hearing loss. Blood and urine tests that look at kidney function are also important because of the genetic conditions that involve both the ears and kidneys. A blood test for thyroid function may be done to screen for Pendred syndrome, which is associated with goiter.
Genetic Testing: Chromosome tests may be done in some cases when a person has other physical or developmental problems. The chromosomes can be examined under the microscope to see if a chromosome or part of a chromosome is missing or duplicated. However, in order for an abnormality to be seen under the microscope, it must be fairly large and involve many genes. At this time, geneticists cannot see individual genes, such as the gene for Waardenburg syndrome, so this test cannot be used to diagnose a hearing loss caused by a single gene.
The Results of the Evaluation
If It's Genetic: When the whole evaluation process has been completed, the results are shared with the family. If the hearing loss is genetic, the way it is inherited will be discussed. If a syndrome is identified, the geneticist describes the medical or physical features, and if there are any, concerns for future medical issues and how they can be managed. The geneticist can assist in finding resources and further information. Sometimes genetic testing uncovers milder symptoms of syndromes not previously diagnosed, such as hearing loss related to osteogenesis imperfecta or Down's Syndrome.
If It's Still Unknown: Unfortunately, the cause of the hearing loss may still be unknown even after an extensive medical genetic evaluation.. The most common genetic cause would be autosomal recessive inheritance, in which the person with the hearing loss has two genes for hearing loss. Each of the parents would have only one gene for hearing loss, which would not affect their hearing. They would have inherited that gene from one of their parents, and so on back through generations. Only when both parents have the gene, and both pass it on to a child would the hearing loss be evident. There would be a 25% chance with each pregnancy that they could have a child with hearing loss. A person with autosomal recessive hearing loss would have a very small chance of having a child with hearing loss, unless they married someone with exactly the same genes for hearing loss or with a dominant form of hearing loss.
It would also be possible that a person with hearing loss could have a dominant gene that is new to him or her and which arose through the process of mutation. No one else in the family, including the parents, would have the gene, but the person with the new hearing loss gene would have a 50% chance of passing it on to a child. Finally, if the person with the hearing loss is a male, it is possible that the hearing loss is X-linked, or passed on through the female. The mother could "carry" the gene, or it could have appeared for the first time in the boy with hearing loss.
What Is the Chance of Hearing Loss in Future Children? These estimated risks are based on studies of many families with similar family histories. For example, if the family is a hearing couple who has had one child who is profoundly deaf, the chance that the next child would be deaf is about 10% [F.R. Bieber & W.E. Nance. 1978. L.G. Jackson, R.N. Schimke, (Eds) Clinical Genetics: A source book for Physicians. NY; Wiley.] If both parents are deaf, and the cause of their deafness is unknown, the chance that their first child would be deaf would also be about 10%. Genetics professionals in the United States support the idea of "non-directive" counseling, which means that genetic counseling is meant to be informative and supportive. It is not meant to tell people what to do or whether or not to have children. These principles have been adopted by the major professional societies for genetics professionals.
Different Perspectives: Particularly in the case of hearing loss, people may have quite different attitudes about deafness in their family. For example, some hearing parents might be concerned about having another child who is deaf, while others may feel that the hearing loss would not pose a problem, but would want to know if any other medical problems might be involved. Similarly, deaf parents may feel comfortable about their own abilities, but would prefer not to have a deaf child, whereas other deaf parents may be more concerned about the challenges of raising a hearing child.
Common Forms of Syndromic Deafness
Recent discoveries about the genetics of hearing loss have substantially increased the information available through genetic testing. For example, recent discoveries about mutations in the Connexin 26 gene have shown that this gene may be responsible for 20-30% of all congenital, nonsyndromic hearing loss. There are several different types of mutations in this gene which can contribute to hearing loss. One gene mutation called is found in 2-3% of Caucasians of European descent. Another mutation of the Connexin 26 gene referred to is found in almost 5% of the Ashkenazi Jewish population. Usually, mutations in the Connexin 26 gene are recessive, meaning that both the mother and the father of the baby need to have the mutation for it to cause a hearing loss in the baby. Hearing loss due to mutations of the Connexin 26 gene is almost always congenital, severe to profound, not progressive, and occurs without any other medical problems (nonsyndromic).
"The NDCS does not support the genetic screening of whole populations for genetic conditions, with the consequent risk of moving towards a society in which difference is no longer accepted or tolerated."
The Joint Committee on Infant Hearing recommends that families of all babies with hearing loss for whom there is not a clear-cut etiology should be given the option of genetic evaluation and counseling by a medical geneticist. Making sure that all these infants with hearing loss receive competent genetic evaluation and counseling can have many benefits for the baby and family. Such procedures can help the family avoid unnecessary and often costly clinical tests necessary to rule out conditions associated with syndromic deafness, determine the cause of hearing loss which can dispel misinformation and allay parental guilt, (i.e. "was it that fever I had before I knew I was pregnant?", and develop an individualized treatment strategy to ameliorate the complications of various syndromes (e.g., Vitamin A therapy may be beneficial to persons with Usher syndrome in slowing retinal degeneration, or treatment of children with Long QT Syndrome can minimize cardiac complications).
The benefits of making sure genetic testing and evaluation is offered to parents of children with hearing loss are substantial. However, appropriate explanations of the genetics of hearing loss can be complicated and difficult to understand. An excellent pamphlet is available from the Harvard Medical School Center for Hereditary Deafness and can be viewed or downloaded at www.infanthearing .org/ehdi/index.html . Finding a place to do genetic testing can also be difficult for families who do not live near major population centers.
The Ethics of Genetics and Deafness
Certainly, the question of ethics arises in relation to genetic testing. A recent article in the Journal of Medical Genetics (2002; 39: 449-453) entitled "Attitudes of deaf and hard of hearing subjects towards genetic testing and prenatal diagnosis of hearing loss" raises some of these questions, including preferences for hearing or deaf/hard of hearing children, abortion, and suspected effects of genetic testing on deaf culture
I like the position statement of the National Deaf Children's Society on this subject, which states that: "The NDCS does not support the genetic screening of whole populations for genetic conditions, with the consequent risk of moving towards a society in which difference is no longer accepted or tolerated."
Will I pursue testing for our daughter? While the chances are 50/50 to find anything helpful for her, (she is far past infancy), testing may contribute to the overall body of knowledge in hearing loss, so we probably will.
Resources for Genetic Testing:
Gallaudet University is looking for volunteers for genetic testing (blood test only) in collaboration with Virginia Commonwealth University . As part of a research project, this testing is free of charge. Right researchers are testing for Connexin 26, a common gene for deafness. Please contact the Project Coordinator, Ms. Ginger Norris at email@example.com or at 800 451-8834, ext 5258 by phone. Ms. Norris will explain the goals of the study and all the details. She then sends consent forms to the family to sign and return. Once the family returns the forms, we send them a kit to bring to their doctor that includes everything they will need to have their blood drawn. We also arrange to have the blood shipped overnight (FedEx) to the lab at Virginia Commonwealth . Results are generally available within 6 months.
The Boys Town Research Registry for Hereditary Hearing Loss - was a previous source of testing but no answer was received from queries at the center before publication. The toll free line listed on the website has been disconnected.
Testing sites throughout the USA : http://www.kumc.edu/gec/prof/genecntr.html .
More information: www.babyhearing.org