Учебники / Genetics and Auditory Disorders Keats 2002

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syndromic hearing loss have been determined by linkage analysis (Mueller, Van Camp, and Lench, Chapter 4). Testing for most of these genes is now available on a research basis and, for some, on a clinical basis.

Genetic testing may be appropriate in a variety of situations and for several reasons. When a syndromic form of deafness is suspected, genetic testing may be able to confirm or rule out a particular syndrome. Hearing parents with one or more deaf children may be interested in testing to identify the cause of deafness in these children. Subsequently, they may want to know about their options for carrier testing for their hearing children and prenatal diagnosis for future pregnancies. When both members of a couple have nonsyndromic autosomal-recessive deafness, they may desire testing to find out whether their chances to have deaf children are near 0% or 100%.

It is important for the genetic counselor to be aware of and be prepared to discuss appropriate clinical tests and research protocols with families. For clinical testing, genetic counselors should be able to explain what type of sample is needed and how much, the cost of the test, and the turn-around time for results. In evaluating a research protocol, genetic counselors should know the inclusion criteria for a study and be able to answer families’ questions, such as: “What does participation require of me?” “Is there any cost to me?” and “Will I get results from the study?” It is also critical that genetic counselors be involved in conveying the results of testing to the family. A person who receives the results of genetic testing may have many questions regarding carrier testing for other members of the family, reproductive options, and treatment. The identification of a specific form of hereditary deafness may also be a very emotional time for the person or the family. It is important that a genetic counselor be the primary point of contact or part of a team of individuals responsible for providing this information to the family.

3.7 Discussion of Diagnosis, Inheritance Pattern,

Prognosis, and Treatment Options

During a genetic counseling session or sessions following the genetic evaluation, the individual or family will be given complete information regarding the diagnosis, mode of inheritance, prognosis, reproductive implications, treatment options, options for prenatal diagnosis, and other recommended options for support or follow-up. Particular attention is paid to providing this information in a manner that is sensitive to the individual’s needs and the emotional state of the individual or family. The decision-making process regarding reproductive and treatment options for hereditary deafness may be strongly influenced by the cultural identification and psychosocial needs of hearing parents of a deaf child or deaf adults who identify with the Deaf community. In the non-directive and supportive atmosphere provided by a sensitive and responsive genetic counselor, individuals or families are

encouraged to absorb as much medical and genetic information as they can understand, consider possible courses of action, and begin the decisionmaking process for any choices that must be made. Arrangements for professional sign language or oral interpreters will be made for deaf and hard of hearing children or adults who require these services. It is important in genetic counseling situations that family members not be used as interpreters. Genetic counselors are also given training in providing information in a non-directive fashion that is sensitive to different reproductive preferences or cultural differences. This is an especially important consideration when providing counseling to deaf individuals (Arnos et al. 1991). In providing non-directive counseling for deaf couples, for example, genetic counselors must be aware that word choice can convey cultural bias. Use of the word “chance” instead of “risk” for having a deaf or hearing child is neutral terminology. The use of such terminology enhances openness and communication because it implies that assumptions are not being made about how the couple may feel about having deaf or hearing children. Other examples include the use of the terms “deaf,” “hard of hearing,” and “hearing” when referring to family members instead of the medicalized terms “affected” and “unaffected.”

The genetic counseling session may take place during one visit or may require several visits. Some families are seen for follow-up counseling to assess changing medical aspects, psychosocial concerns, or new advances in genetic screening and testing. Because of the differing needs of families, genetic counseling sessions are unique to every family in terms of content, approach, and types of support provided. Many families can benefit from referrals to support groups, communication specialists, or educators, particularly parents with a young deaf child who need guidance regarding communication and educational options and opportunities to network with other parents of deaf children. Genetic counselors often work together with audiologists, social workers, and psychologists to assist families in obtaining this type of information.

4. Recurrence Risks/Empirical Risk Estimates

The genetic counselor will often need to rely on empirical risk estimates when informing families about recurrence risks. For hearing parents whose first child is deaf due to an etiology that cannot be determined after genetic evaluation, and who otherwise have a negative family history, an empirical risk estimate of 9% would be given. A deaf couple would be given an empirical risk of 10% for their first child to be deaf, given that an etiology could not be determined in either of them. Empirical risks are also helpful in many other situations (Bieber and Nance, 1979). However, the ability to provide accurate information regarding recurrence risks to hearing parents of a single child with hearing loss and to adults with hearing loss

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has been greatly assisted by the availability of genetic tests for common forms of genetic deafness. In the future, there will be a decreasing need for genetic counselors to rely on empirical risks when providing information to families.

5. The Future is Now: Genetics Technology and the Genetic Counseling Process

As described in several of the preceding chapters, advances in the identification and characterization of genes for hearing loss are occurring very rapidly. These technologies are beginning to have a profound effect on the genetic counseling process. Because these advances are relatively new, many genetic counselors are only beginning to learn about the availability of clinical diagnostic tests and research-based tests available for hearing loss. For some conditions, carrier testing and prenatal diagnosis is now possible and is being offered by some programs.

It is important that geneticists, as well as other professionals involved in the health care of individuals with hearing loss, consider the ethical implications associated with the utilization of genetics technology. As pointed out by Nance (1993), the genetics/medical community, deaf and hard- of-hearing people, and parents of young deaf children may have widely divergent views regarding the appropriate use of genetics technology. While there are many benefits of the availability of genetic testing to diagnose both syndromic and nonsyndromic forms of deafness, there are many ethically challenging situations that can arise. At what point should the decision be made to offer genetic testing on a clinical basis rather than a research basis? At what point should carrier testing and prenatal diagnosis be offered? Should hearing parents at risk for a deaf child be given the option of prenatal diagnosis and termination of the pregnancy? Should these parents first be given detailed information about the effects (both negative and positive) of deafness upon the lives of children? Should deaf parents who desire to have deaf children be given this option through genetic testing, prenatal diagnosis, and selective termination of a hearing fetus? Although this situation may only rarely arise, it is within the realm of possibilities. Now that it has become evident that connexin 26 mutations are very common causes of congenital deafness, deaf people may seek testing for the purposes of avoiding having deaf children or, alternatively, improving their chances of having deaf children. Either of these goals could be accomplished simply by the deliberate choice of a marriage partner without or with mutations in the connexin 26 gene. How do we best encourage an open dialogue between the medical/genetics community and deaf and hearing consumers regarding these issues? Should we encourage this type of dialogue at all? These and other issues need to be considered by

a daughter with a high-frequency hearing loss. M.S.’s other nieces and nephews are hearing. M.S.’s mother is hearing, and her father has a highfrequency hearing loss. His paternal grandfather was said to be “very hard of hearing.” No audiometric information to document degree or progression of the hearing loss is available for these relatives.

D.S. is one of four deaf siblings and is the product of deaf parents (Fig. 9.1). One of his sisters married a deaf man from a deaf family and has two deaf sons. Another sister married a deaf man with a family history of deafness and has one deaf and one hearing child. The third sister married a hearing man of deaf parents and has one hearing son. D.S.’s parents each have a deaf brother and other hearing siblings. They were both born to hearing parents.

6.1.4 Physical Examination

M.S. is a petite woman who is said to be smaller than her siblings. Funduscopic examination revealed mottled coloration of her retinas. There was no audible heart murmur. The rest of the examination was within normal limits. D.S.’s physical examination was within normal limits with no evidence of a genetic syndrome.

6.1.5 Clinical Diagnosis and Recommendations

M.S. was diagnosed as having congenital rubella syndrome (Table 9.2). D.S. was diagnosed as having nonsyndromic, autosomal recessive, sensorineural hearing loss. It is also likely that an autosomal-dominant form of nonsyndromic sensorineural hearing loss is present in M.S.’s family.

6.1.6 Genetic Counseling Issues

Genetic counseling in this situation would include a discussion of congenital rubella syndrome (CRS) and why this is the likely cause of M.S.’s deafness. There is a 50% chance that M.S. has also inherited the gene for autosomal-dominant high-frequency hearing loss from her father, but that it is masked by the CRS. If she has inherited the gene, there is a 50/50 chance with each pregnancy that she will pass on that gene to her child.

TABLE 9.2. Congenital rubella syndrome

Fetal exposure to a maternal rubella infection may cause changes in several organ systems, most commonly the ear, heart, and eyes. Infants may have a sensorineural deafness. They may have a congenital heart defect, usually patent ductus arteriosus, pulmonary stenosis, ventricular septal defect, or atrial septal defect. Common eye findings in congenital rubella syndrome (CRS) are cataracts and congenital glaucoma. Other features associated with CRS include small stature, jaundice, enlarged liver and spleen, small head, learning disabilities or mental retardation, anemia, low platelet count, changes in the hardening of the long bones, and a rash.

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During the genetic counseling session, a detailed description of autoso- mal-recessive inheritance would be provided. All of D.S.’s future children will be carriers of the gene causing his deafness. Because D.S. and M.S. have different types of hearing loss, their chances of having congenitally deaf children appear to be low. However, D.S. has an apparently common form of hearing loss as is evident by the fact that his mother and father and one sister married someone with the same type of hearing loss. Therefore, it is possible that M.S. may be a carrier of the same type of deafness as D.S., in which case they would have a 50/50 chance of having deaf or hearing children with each pregnancy.

This couple’s perception of deafness and their desires for deaf or hearing children would be explored. They may have never considered the possibility of having a hard of hearing child and may be surprised to learn about this chance. In addition, they may have suspected that their chance to have deaf children was high because D.S. has a deaf family.

They would be referred to a genetics center performing molecular genetic studies of nonsyndromic deafness. Depending on whether the testing at that center is performed on a clinical or research basis and whether D.S. has a form of deafness for which there is currently a test, this testing may or may not aid this couple in decisions about family planning.

6.1.7 Overview of Case 1

This case demonstrates the complexity of counseling deaf couples and the potential ability of molecular testing to aid genetic counselors in providing the most accurate recurrence risk information possible. There are at least three different types of hearing loss in this family. Identifying the gene that caused D.S.’s deafness and testing M.S. to see whether she carries that gene will allow a genetic counselor to determine whether the couple’s chance to have a deaf child is the same as the general population’s chance of 1 in 1000, as suspected based on the clinical information, or whether that chance is actually 50%. In addition, without molecular testing, there is no way to know prior to M.S.’s having children whether she has inherited a gene from her father for high-frequency hearing loss. This case also addresses the issue of deaf people’s perceptions of their chance to have deaf children and their desires to have deaf or hearing children, which vary greatly from individual to individual.

6.2 Case 2

S.K. is a 23-year-old, profoundly deaf, white female who is self-referred to learn more about why she is deaf and why she has different colored eyes. She was born deaf and attended residential schools for the deaf for most of her life. S.K. currently is not married and does not plan to have children in the near future, although she is curious about her chance to have deaf or hearing children, should she decide to have children in the future.

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gray hair just above the forehead. Her left eye was blue and her right, brown. There was no dystopia canthorum. Her nose was well formed. Her skin was evenly pigmented.

6.2.5 Clinical Diagnosis and Recommendations

A diagnosis of Waardenburg syndrome type II was made. (see Table 9.3.) Because of the potential implications for family planning, genetic evaluation of other family members (especially S.K.’s aunt and uncle) would be recommended to confirm or rule out Waardenburg syndrome.

6.2.6 Genetic Counseling Issues

During this genetic counseling session, the features of Waardenburg syndrome (WS) would be discussed. A clear explanation would be given to S.K. to help her understand that WS has caused both her deafness and different colored eyes and has also caused other pigmentary changes in her family members (white forelock, skin hypopigmentation and early graying of the hair). A detailed explanation of autosomal-dominant inheritance with variable expression would take place. S.K., as well as anyone else in her family with Waardenburg syndrome, would have a 50% chance of having a child with WS. There is a 50% chance that a person with WS type II will be deaf. Therefore, S.K. has a 25% chance with each pregnancy to have a deaf child. S.K. would be advised to return for genetic counseling when she marries or is planning to have children. She has indicated that she prefers to marry another deaf person and would be interested in finding out about their chances of having a deaf child.

6.2.7 Overview of Case 2

This case demonstrates the importance of making an accurate diagnosis of a syndrome. The associated features of Waardenburg syndrome are rarely of medical significance and may be subtle; someone not trained in genetics

TABLE 9.3. Waardenburg syndrome

Waardenburg syndrome (WS) is characterized by sensorineural hearing loss that may be mild to profound and unilateral or bilateral, heterochromia (often one blue and one brown eye) or bright blue eyes, congenital white forelock or premature greying, and hypopigmented skin. In rare instances, individuals with Waardenburg syndrome have serious medical complications, such as Hirschsprung’s disease or spina bifida. There are two common forms of Waardenburg syndrome, types I and II, which are distinguished by the presence or absence of dystopia canthorum and by the frequency of hearing loss. Waardenburg syndrome type I is characterized by dystopia canthorum. About 20% of people with WS type I have a hearing loss. People with Waardenburg syndrome type II have normally spaced eyes, and about 50% have a hearing loss. All forms of Waardenburg syndrome are inherited as a dominant trait.