Genetic Counseling: Genetic Testing, Family History and Psychosocial Evaluation

When Sven meets with Anya and David to talk about their three-year-old boy's diagnosis of DMD, he learns that they also have a 10-year-old son and a seven-year-old daughter, and that they hope to have another child in the near future. Sven explains to the couple that DMD is caused by a mutation in the dystrophin gene, which is located on the X chromosome. He reminds them that there is nothing either of them did to cause their son to inherit this disorder. He then explains X-linked recessive disorders, and why, except in rare cases, such disorders only manifest in boys.

Next, Sven tells Anya and David about the patterns of inheritance associated with DMD. He notes that females, who have two X chromosomes, are said to be carriers when they have one X chromosome with the normal gene and one X chromosome with the mutant gene. Because of the presence of the normal copy, female carriers typically do not develop the disease. On the other hand, because males have only one X chromosome and they inherit this chromosome from their mother, any male children of a female carrier of a DMD mutation have a 50% chance of being affected with DMD. Sven makes sure the couple understands that if Anya is a carrier of a DMD mutation, for any future pregnancies, her risk for having a child with DMD is 25%, or 1 in 4 overall. Sven also points out that if Anya is a carrier, then their daughter may also carry the faulty dystrophin gene on one of her two X chromosomes, and may pass it along to her future children.

Sven helps Anya and David sort through many questions related to their situation: What is the prognosis for their son? Will they need help caring for the boy? What treatment and support resources are available for DMD families? Should they have their daughter's carrier status determined now, or let her decide whether to be tested when she is an adult? Do they want Anya to undergo genetic carrier testing so they can better predict their risk of having another affected son? (Note that approximately one-third of women who have a son with DMD but no family history of the disease are not carriers of a DMD mutation. Their sons are therefore considered to have a de novo or "new" mutation, and the woman's chance of having another affected child is no greater than that of the general population.) If Anya is found to be a carrier and the couple decides to have more children, would they consider using in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD) to select an unaffected embryo for implantation? Might they instead use some other form of medical technology to increase their chances for having a girl? Would they test an ongoing pregnancy for the dystrophin mutation? These questions are ultimately theirs to answer, but Sven must provide any information necessary to help Anya and David reach a decision in a client-centered, nondirective way.

Sven's session with Carla is very different. Carla is a 37-year-old mother of three young daughters who has been diagnosed with breast cancer. She is worried about her daughters and wants to know whether they are at risk for developing the same disease. Sven knows that genetic counseling for cancer risk assessment requires many steps. While the inheritance patterns of mutations that are associated with cancer are straightforward and usually autosomal dominant, the actual risk for the individual to develop cancer, even if the mutations are present, is more complex. This is because development of the disease is almost always due to a combination of genetic and environmental factors, many of which are not yet known.

To determine whether Carla's daughters are at an increased risk for breast cancer, Sven must first gather personal medical and family history data to look for evidence of an inherited risk for cancer. Using that information, Sven must then assess the likelihood that Carla has a mutation in one of the breast cancer susceptibility genes, BRCA1 and BRCA2, making sure that she understands that this risk assessment is based on her family history, the age at which she was diagnosed with cancer, her ethnic background, and various other factors.

If Sven determines that Carla's situation meets the criteria to be offered testing, he will obtain her informed consent to be evaluated for mutations in BRCA1 and BRCA2. Sven must feel confident that Carla fully understands the risks, benefits, and limitations of the knowledge that the testing may bring, including matters related to insurability and discrimination. Because of the potentially powerful information obtained from such genetic testing, Sven and Carla must also "contract" about how the results of the testing will be disclosed and to whom. Should Carla share this information with her daughters to prepare them for what might develop, and so they know more about their own cancer risk? What other family members might also be at risk for having the mutation? How will Carla communicate this information to them accurately without alarming them? Carla will also need to make lifestyle and medical decisions about her own health, such as considering prophylactic mastectomy to reduce her risk for developing another tumor in her breast. Finally, Sven must be sure Carla knows about prevention strategies and is aware of environmental factors and lifestyle choices that may increase her or her daughters' cancer risk.

Bali is 25 and pregnant with her first child. The results of her triple screen test, a blood test that measures certain fetal protein levels, shows an elevated risk for having a baby with Down syndrome. Because of this elevated risk, Bali's doctor wants her to undergo amniocentesis, which will allow a definitive diagnosis of Down syndrome. The cut-off for calling a woman's risk "elevated" and offering amniocentesis is anything at or above the risk of fetal loss due to the amniocentesis procedure (generally 1 in 200). This is also the age-related risk that any 35-year-old woman has of having a baby with Down syndrome. Therefore, in many places, woman over the age of 35 are routinely offered amniocentesis for every pregnancy.

Bali tells Sven that she knows that babies with Down syndrome are usually born to older mothers, and she therefore believes amniocentesis is unnecessary. During their session, Sven tells Bali her age-related risk for having a baby with Down syndrome, which is approximately 1 in 1,300. Sven then tells Bali about the limitations of the triple screen test and how her increased risk was calculated. Next, they talk about the risks of the amniocentesis procedure. Sven describes the chromosomal basis of Down syndrome and what Bali might expect in caring for a special needs child, putting all of this in the context that her estimated risk is still low.

Finally, Sven tries to assess Bali's personal emotions about, perceptions of, and experiences with Down syndrome, to help her decide whether further testing is right for her. The availability of testing during pregnancy is discussed without persuasion, and the choices Bali has for this pregnancy based on the information from the amniocentesis are discussed.