Cracking the DNA Code: Genetic Testing Case Examples of Interest to Elder Law and Special Needs Planning Attorneys

Transcription

1 Fall Cracking the DNA Code: Genetic Testing Case Examples of Interest to Elder Law and Special Needs Planning Attorneys By Kelli Swan, MS, and Jaellah S. Thalberg, MS I. Introduction II. Newborn Screening A. Case: Steve and Molly Genetics of PKU Newborn Screening for PKU Reproductive Decisions B. Case: Mike and Tanya Genetics of Hearing Loss Newborn Screening for Hearing Loss Is Deafness a Disability? III. Noninvasive Prenatal Screening A. Case: Altan The Technology of Noninvasive Prenatal Screening Prenatal Testing for Down Syndrome Standardization of Testing for Down Syndrome During Pregnancy Noninvasive Prenatal Screening and Down Syndrome IV. Hereditary Cancers A. Case: Susan Genetics of Hereditary Breast and Ovarian Cancer Syndrome Previvor Concept Affordable Care Act and BRCA Testing V. Alzheimer s Disease A. Case: Shira Brief Genetic Background of Alzheimer s Disease The Right Test for the Right History Informed Consent Genetic Information Nondiscrimination Act and Insurance VI. Conclusion Endnotes Kelli Swan, MS, is a diplomat of the American Board of Genetic Counseling and a board certified genetic counselor. She received an M.S. in Genetic Counseling from Northwestern University in 2009 and an M.A. in Medical Humanities and Bioethics from Northwestern University in She specializes in cancer genetics and works for Myriad Genetics, Inc., in Salt Lake City, as a Regional Medical Specialist. She is also a member of the National Society of Genetic Counselors Ethics Advisory Group. Jaellah S. Thalberg, MS, is a diplomat of the American Board of Genetic Counseling and a board certified genetic counselor. She received an M.S. in Genetic Counseling from Northwestern University in 2012 and an M.A. in Medical Humanities and Bioethics from Northwestern University in She specializes in prenatal genetics and works for the Legacy Health system in Portland, Oregon.

2 104 NAELA Journal Volume 11, Number 2 I. Introduction Gregory Wilcox and Rachel Koff aptly note in their article in this issue of NAELA Journal, Genetics is no longer only a topic for biology courses and science magazines; it can be used to great effect in individuals. Genetic testing has evolved from being the subject of science fiction novels into a standard of care in American health care. Routine genetic testing begins at birth, when nearly all babies are screened for a variety of genetic conditions. Continuing throughout adulthood, an increasing number of individuals are being exposed to genetics and genetic testing. One s genetic information can help direct his or her medical care and management throughout all stages of life. Evidence that genetic testing is becoming a standard of care is illustrated by many professional society guidelines. The American College of Medical Genetics and Genomics (ACMG) advocates that individuals with a cognitive impairment or individuals diagnosed on the autism spectrum undergo a genetic evaluation [1-3].* The American College of Obstetricians and Gynecologists (ACOG) recommends that all pregnant women be offered genetic testing for conditions such as Down syndrome or cystic fibrosis [4, 5]. The National Comprehensive Cancer Network (NCCN) recommends that women diagnosed with breast cancer at or under the age of 45 and women diagnosed with ovarian cancer be offered testing for the breast cancer genes, BRCA1 and BRCA2, which can help guide surgery and treatment options [6]. While professional societies guidelines have cemented genetic testing s role in the medical community, mainstream media coverage of genetic conditions has increased genetic testing awareness in the general public. Growing awareness of and technological advances in genetic testing make it very likely that Elder Law attorneys will work with clients who have experienced genetic testing and/or genetic conditions in some way. The authors hope that this article will help Elder Law attorneys better understand the uses, benefits, and limitations of genetic testing to help them support such clients. Developing this understanding will become even more important as genetic technologies evolve. In this article, which is intended to supplement the article in this issue written by Wilcox and Koff, five fictional case examples illustrate the value of genetic information in our lives and highlight certain issues that may be of interest to Elder Law attorneys. Our dive into genetic testing begins with an explanation of newborn screening, which is designed to identify newborns with specific diseases or disabilities and thus enable prompt treatment. Next, we consider how newborn screening has expanded to include conditions such as hearing loss and deafness, which raises the question of how one defines disability. We then explore cultural views on disability by considering prenatal genetic testing recommendations for Down syndrome using the newly available noninvasive prenatal screening (NIPS) and how this technology might impact Down syndrome in the future. Finally, we consider the utility of genetic testing for adult-onset conditions, such as breast and ovarian cancer and Alzheimer s disease. II. Newborn Screening More than 50 years ago, screening of newborn babies for select medical conditions * Note about the citations in this article: The authors use end notes consistent with the Annotated EndNote X7 style rather than the Association of Legal Writing Directors Guide to Legal Citation used in NAELA Journal.

3 Cracking the DNA Code: Genetic Testing Case Examples of Interest Fall 2015 to Elder Law and Special Needs Planning Attorneys 105 began to make its way into routine medical care. Beginning with just one disorder, phenylketonuria (PKU), newborn screening has expanded to include more than 50 conditions, with the specific panel of newborn disorders screened for varying from state to state [7]. This routine testing involves analyzing the newborn s blood, which is collected from a heel stick shortly after birth (typically around 24 hours of age). Newborn screening is not used for diagnosing these genetic conditions. When a newborn receives a positive screen, the family is contacted to coordinate follow-up testing to confirm or rule out the disorder. If a diagnosis is confirmed, prompt treatment is started. Newborn screening strives to achieve the fundamental goal of reduced mortality, morbidity, and disability in the screened infant by fostering early detection, diagnosis, and treatment of certain disorders [7, 8]. Newborn screening has been praised as being a victory of medicine. As we attempt to show the value of newborn screening, we also hope to illustrate some of the more complex issues of newborn screening that challenge the perception of what constitutes a disability and what disorders require prompt treatment. A. Case: Steve and Molly Steve and Molly are proud new parents of their first child, Emma. When Emma is 8 days old, they receive a phone call from the local hospital informing them that Emma s newborn screen came back positive for the genetic condition PKU. They are referred to a local genetics clinic, and additional testing confirms that Emma has PKU. Emma is started on a special formula and diet that will prevent her from developing mental retardation, which can result from PKU. 1. Genetics of PKU PKU is a rare inherited disorder affecting approximately 1 in 15,000 people. In the United States, approximately 275 infants will be born with the disease per year [9]. In the human body, proteins perform most of the work in our cells and are required for the structure, function, and regulation of the body s tissues and organs. Amino acids, usually obtained from the food we eat, are the building blocks of protein. PKU is a metabolic disorder that results in the inability of the body to use the amino acid phenylalanine (Phe). Normally, the body uses an enzyme called phenylalanine hydroxylase (PAH) to convert Phe to another amino acid, tyrosine. Someone with PKU lacks the PAH enzyme, which results in Phe accumulating in the blood and tissues because it cannot be converted tyrosine. High Phe levels are toxic to the central nervous system and can cause severe complications. If left untreated, PKU can cause irreversible mental retardation, hyperactivity, autistic-like features, and seizures [10, 11]. Newborns such as Emma who are diagnosed with PKU are immediately started on a specific lifelong diet. Although some Phe is needed for normal growth, the diet consists of foods low in Phe, and Phe levels are measured periodically. High-protein foods are avoided, and special Phe-free formulas are available for all age groups [11]. The goal of this diet is to maintain normal Phe levels in the body. Until 2007, a low-phe diet was the only treatment for PKU. In 2007, the U.S. Food and Drug Administration (FDA) approved Kuvan, a prescription medication that works to stimulate PAH enzyme activity and thus lowers Phe levels in the body. This medication may not be effective in all patients with PKU, but it provides another option for maintaining normal Phe levels in conjunction with the low-phe diet [12].

4 106 NAELA Journal Volume 11, Number 2 When treatment is started early and strictly maintained, children with PKU can be expected to achieve normal development and live a normal lifespan. Mutations in the PAH gene cause PKU, an autosomal recessive condition. Individuals who have PKU have two PAH mutations, one inherited from the mother and one inherited from the father. Thus, when a baby such as Emma is diagnosed with PKU, we also learn that both parents are carriers of PKU. This means that each parent has one PAH mutation. Carriers such as Steve and Molly do not have PKU but are at risk for having children with this condition. It is estimated that approximately 1 in 50 people are carriers of PKU. Because Steve and Molly are PKU carriers, they have a 25 percent chance of having another child with PKU with each future pregnancy. 2. Newborn Screening for PKU Newborn screening for PKU is performed by determining the Phe levels in the newborn s blood, which is obtained during a heel stick. Virtually 100 percent of PKU cases can be detected by newborn screening [13]. Newborn screening for PKU is widely viewed as a victory for scientific medicine [9]. If PKU is detected in the newborn, treatment with a low-phe diet successfully averts the complications and cognitive impairment caused by PKU. All 50 states currently require newborn screening for PKU. Outside the United States, newborn screening for PKU has become routine in nearly every industrialized nation and has extended into many poorer countries [7, 9]. Because newborns with PKU appear normal, routine screening of all newborns enables early identification of the disorder and prevention of disability. Children such as Emma can now experience normal development and become productive adults[14]. 3. Reproductive Decisions Steve and Molly learned that they are PKU carriers when Emma was diagnosed and have a 25 percent chance of having another child with PKU with each pregnancy. Because they want more children, Steve and Molly decided to pursue testing of the PAH gene, which enables the identification of the specific mutations in the gene they carry. Being able to identify these specific mutations gives Steve and Molly the information they need to make informed reproductive decisions. Stuart Lavery, at IVF Hammersmith Hospital in London, and colleagues describe the decisions such families face when considering starting or enlarging their families [15]. Some couples are willing to accept a 1 in 4 chance of having an affected pregnancy. Others choose to conceive naturally and then undergo more conventional invasive prenatal testing such as chorionic villus sampling [16] near weeks of pregnancy or amniocentesis [17] near weeks of pregnancy. These procedures carry an approximately 1 percent risk of pregnancy loss. If a pregnancy is diagnosed as affected by PKU, couples face the option of either terminating the pregnancy or continuing the pregnancy knowing that their child will need lifelong medical management. Preimplantation genetic diagnosis (PGD) is another reproductive option for these couples. Embryos are produced by the in vitro fertilization (IVF) process and are analyzed for the presence of the affected genes. Embryos free of the disease can then be transplanted into the uterus. This reassures couples from the very beginning of a pregnancy that the child will be unaffected by PKU and enables them to avoid invasive prenatal diagnosis [15].

5 Cracking the DNA Code: Genetic Testing Case Examples of Interest Fall 2015 to Elder Law and Special Needs Planning Attorneys 107 The first successful live birth took place in the United Kingdom following PGD, which detected two mutations in the PAH gene [15]. In general, PGD is more commonly used for diagnosing lethal disorders, and there remains some debate about the appropriate and ethical use of this technology to screen for more chronic, treatable disorders for which effective management is available, such as PKU. B. Case: Mike and Tanya Mike and Tanya, who both have normal hearing, are proud parents of a baby boy, Jack. Before they leave the hospital, they are informed that Jack failed the hearing test that was part of newborn screening. Because of this positive screen, they are referred for more detailed and diagnostic hearing tests. When Jack is 3 months old, these tests confirm that Jack has bilateral permanent hearing loss resulting in deafness. Genetic testing reveals two connexin 26 (GJB2) mutations as the cause of Jack s deafness. At 6 months of age, Jack begins early intervention services and his parents consider pursuing a cochlear implant when he is older. 1. Genetics of Hearing Loss Profound congenital hearing loss is estimated to occur in about 1 in 1,000 births. Forty percent of cases are thought to be due to environmental factors (e.g., trauma to the ear, drug exposure, bacteria) and 60 percent are thought to be due to genetic causes [18]. Genetic causes can be further broken down into nonsyndromic (the deafness is not associated with other clinical findings that constitute a known syndrome) and syndromic (the hearing loss is associated with a known syndrome). Causes of syndromic hearing loss are extensive and include more than 400 etiologies [8]. More commonly, hearing loss caused by a genetic reason is nonsyndromic. Nonsyndromic hearing loss can be further classified by various inheritance patterns within the family. When a baby such as Jack is born with deafness to two parents with normal hearing, an autosomal recessive inheritance pattern is suggested. This is the same inheritance pattern as described previously with PKU. Interestingly, mutations within a single gene, GJB2, give rise to more than half of the genetic causes of profound deafness in the United States [8]. As described in the case example, Jack s deafness was caused by inheriting two GJB2 mutations (one from each parent), and thus we also discover that both Mike and Tanya are GJB2 mutation carriers. For each future pregnancy, there is a 25 percent chance that their baby will inherit both GJB2 mutations and be born deaf. 2. Newborn Screening for Hearing Loss The National Institutes of Health in 1993 recommended that all newborns undergo hearing screening shortly after birth. Numerous professional societies, including the American Academy of Pediatrics and ACMG, and the U.S. Preventive Services Task Force followed in supporting this recommendation [8, 19 21]. As of November 2014, newborn hearing screening is required in 35 states, with another nine states offering screening to all newborns [7]. Underlying these recommendations is a consensus that untreated hearing loss can result in lifelong speech and language deficits. Therefore, early identification of hearing loss and prompt follow-up for those who fail the initial screening is critical in fostering communica-

6 108 NAELA Journal Volume 11, Number 2 tion development [18]. Newborns who fail the initial screening are referred for more extensive hearing loss evaluations and for consultation with a genetic specialist [18]. 3. Is Deafness a Disability? In 2002, the ACMG Genetic Evaluation of Congenital Hearing Loss Expert Panel published a statement on genetics evaluation guidelines for congenital hearing loss [8]. In this statement, the panel asserts that the fundamental goal of well-coordinated newborn screening programs is to reduce mortality, morbidity, and disability in the screened infant [8]. For conditions such as PKU, the benefit of newborn screening seems clear. There is virtually no debate that newborn screening for PKU does indeed reduce mortality, morbidity, and disability in infants with PKU. Hearing loss, specifically deafness, introduces some shades of gray into the benefit of newborn screening in reducing disability in the screened infant. The ACMG panel s statement cites several studies that provide outcome data showing that early detection of hearing loss, accompanied by the introduction of intervention strategies within the first few months of life, results in an infant s subsequent development of language skills that approach the skill levels of their peers who do not have a hearing loss [22, 23]. Many deaf people, however, do not consider themselves as having a disability. Instead, many deaf people consider themselves to be part of a distinct cultural group with its own language, customs, and beliefs. Harlan Lane, professor of psychology with expertise in the culture of the deaf world, shares his perspective that labeling deafness as a disability brings with it needless medical and surgical risks for the Deaf child and endangers the future of the Deaf-World [24]. Lane asserts that labeling a deaf child as having a disability places the child at risk for controversial interventions such as cochlear implant surgery. Cochlear implants are small electronic devices that can help provide a sense of sound to a person who is profoundly deaf or severely hard of hearing. The implant consists of a portion that sits behind the ear and another portion that is surgically placed under the skin [25]. The implant does not restore normal hearing but instead can give a deaf person a useful representation of sounds in the environment and help them understand speech [25]. Since 2002, cochlear implants have been FDA approved for use in children beginning at 12 months. As of December 2014, more than 320,000 people have received implants [25]. In 2000, the National Association of the Deaf (NAD) published a position statement on cochlear implants. An excerpt of its statement follows: The NAD recognizes the rights of parents to make informed choices for their deaf and hard of hearing children, respects their choice to use cochlear implants and all other assistive devices, and strongly supports the development of the whole child and of language and literacy. Parents have the right to know about and understand the various options available, including all factors that might impact development. While there are some successes with implants, success stories should not be over-generalized to every individual [26].

7 Cracking the DNA Code: Genetic Testing Case Examples of Interest Fall 2015 to Elder Law and Special Needs Planning Attorneys 109 The position statement also highlights different perspectives on disability between the medical and deaf communities. Many within the medical profession continue to view deafness essentially as a disability and an abnormality and believe that deaf and hard of hearing individuals need to be fixed by cochlear implants. This pathological view must be challenged and corrected by greater exposure to and interaction with well-adjusted and successful deaf and hard of hearing individuals [26]. These differing perspectives on what constitutes a disability raises some interesting questions about conditions selected to be part of newborn screening and the urgency and proper course of treatment for infants who screen positive for these conditions. It also reinforces the need for culturally sensitive genetic counseling surrounding discussions of disability, prenatal testing, and reproductive technologies related to deafness. A. Case: Altan III. Noninvasive Prenatal Screening Altan is a 37-year-old woman who is 12 weeks pregnant. At her most recent doctor s appointment, she was offered a new type of screening, called noninvasive prenatal screening (NIPS), in which her blood would be tested to determine whether her baby has a high likelihood to be born with Down syndrome. Altan s doctor told her that this testing is routine during pregnancy and, because there is no risk to the baby, it would be a good idea to proceed because she is older than 35. Altan is not sure if she wants prenatal screening for Down syndrome but agrees to the blood test because her doctor recommended it. 1. The Technology of Noninvasive Prenatal Screening Prenatal screening for genetic conditions has long focused on identifying pregnancies with the greatest chance of being affected by Down syndrome. Historically, diagnostic testing, such as amniocentesis, was offered to women 35 years of age and older because the chance of Down syndrome affecting a pregnancy increases with maternal age. When the mother is 35 years old, the chance of a fetus having Down syndrome is approximately 0.5 percent; when she is 40, approximately 1 percent; and when she is 45, approximately 3 percent. Amniocentesis was the first option that was available to test a fetus for Down syndrome. Amniocentesis is an invasive procedure in which a needle is used to withdraw some of the amniotic fluid that surrounds the fetus in order to analyze the chromosomes. Because this procedure is invasive, there is a chance of miscarriage (less than 1 percent). Amniocentesis is a diagnostic test, and diagnostic tests are more accurate than screening tests. Since the development of amniocentesis, other blood-based screening options have become available that screen for Down syndrome and other conditions. These blood-based screening options, however, are not as accurate as the invasive diagnostic options. NIPS is a screening test that became clinically available in 2011 in which small fragments of placental DNA in maternal blood are analyzed. NIPS can be conducted as early as

8 110 NAELA Journal Volume 11, Number 2 the 9th or 10th week of pregnancy. NIPS can screen for Down syndrome with no risk to the fetus, with a level of accuracy previously unseen with blood-based screening options. Down syndrome is caused by having three, instead of two, 21st chromosomes. When a fetus has an extra 21st chromosome, the representation of DNA fragments from the 21st chromosome in the maternal blood is usually higher. Complex statistical analysis determines whether the amount of DNA fragments is significantly higher. If it is, the fetus is highly likely, but not certain, to have Down syndrome. In a woman considered high risk [27], a screen positive NIPS result usually indicates there is a greater than 90 percent chance her baby will be born with Down syndrome. It is recommended that all women considering NIPS receive prescreen and postscreen genetic counseling and that positive results be confirmed with diagnostic testing, such as amniocentesis. This is because NIPS can produce false positive as well as false negative results. The technology behind NIPS is still in its infancy, but it is predicted that one day it will be powerful enough to screen for hundreds of genetic conditions. 2. Prenatal Testing for Down Syndrome Although other genetic conditions can be identified through prenatal testing, Down syndrome is arguably the most recognizable condition associated with these technologies. Down syndrome is the most common known cause of intellectual disability, and roughly 1 in 700 children are born each year with this condition [28]. More than 400,000 individuals with Down syndrome live in the United States [28]. Down syndrome is a condition characterized by mild to severe cognitive impairment, common physical characteristics, and an increased risk for specific health complications. Most individuals with Down syndrome are mainstreamed into schools and live fulfilling lives [28]. Down syndrome is one of the few causes of intellectual disability that is recommended to be routinely screened and tested for during pregnancy, yet it is just one of many genetic conditions that can cause cognitive impairment [4, 29]. Other genetic conditions, such as fragile X syndrome, could be screened for prenatally yet universal screening during pregnancy is not recommended, as it is with Down syndrome [30]. Prenatal screening has focused on the identification of Down syndrome due to a number of factors, including the relatively common frequency of Down syndrome, the fact it is an easy condition to recognize because of the common physical characteristics, and the widespread cultural stereotypes surrounding the condition. When prenatal testing options for Down syndrome were being developed, there was a largely negative societal attitude toward having a child with Down syndrome. According to historian David Wright, research studies conducted in the 1950s 1980s concluded that individuals with Down syndrome would negatively impact the family unit and the development of normal children [31]. The medical community, the government, and many families often viewed Down syndrome as a preventable tragedy [31]. While Down syndrome has been historically targeted for prenatal testing, societal attitudes and acceptance have shifted toward greater acceptance of individuals with Down syndrome in the last generation or so. Down syndrome advocacy helped foster a medical community that shifted its views from a largely negative to a more neutral outlook for those with Down syndrome. Even as attitudes toward Down syndrome are changing, the medical recommendation that all women be offered testing for Down syndrome during pregnancy remains.

9 Cracking the DNA Code: Genetic Testing Case Examples of Interest Fall 2015 to Elder Law and Special Needs Planning Attorneys Standardization of Testing for Down Syndrome During Pregnancy When Altan s doctor offered her screening for Down syndrome during her pregnancy, the doctor was providing appropriate prenatal care. Prenatal testing (both diagnostic and screening) for Down syndrome has become routine during pregnancy as a result of various social and legal factors. Multiple legal cases helped set the precedent for offering prenatal testing and screening for Down syndrome during pregnancy. For example, the legalization of abortion allowed families to decide whether they wanted to continue or terminate a pregnancy affected with Down syndrome. After Roe v. Wade, families could decide, to a certain degree, what type of children they were willing to accept. If a woman age 35 or older was not provided the option of amniocentesis or informed of her risks, her obstetrician could be found negligent or families could file wrongful birth lawsuits, as evidenced in the 1970s and 1980s [32 35]. In response to court rulings that a health care provider was negligent if he or she did not offer testing for Down syndrome, ACOG released practice guidelines recommending offering testing for Down syndrome to pregnant women over the age of 35 [36]. Subsequently, ACOG recommended that all pregnant women be offered screening and diagnostic testing for Down syndrome [4] and, even more recently, that NIPS be offered to all pregnant women considered at high risk for having a pregnancy affected with Down syndrome [37]. 4. Noninvasive Prenatal Screening and Down Syndrome Although it is a standard of care to offer prenatal testing for Down syndrome to all pregnant women, many families find this recommendation concerning. With the introduction of NIPS, noninvasive screening for Down syndrome became significantly more accurate and many families wonder how NIPS will impact Down syndrome. Professional medical group recommendations to offer NIPS to high-risk women may inappropriately promote the idea that testing is always in the best interest of the patient and some women may interpret this to mean that they should undergo testing. Merely offering a test can imply that one should undergo testing. One study found that close to half of women did not realize that prenatal screening was optional [38]. Approximately 20 percent of women base their decision to test solely on their doctor s recommendation [39]. Others may feel stigmatized for declining testing. For example, women are rarely asked their motives for proceeding with prenatal testing, but when they decline, they are often forced to defend their choice [40]. Some parents may feel pressured to proceed with NIPS because it involves only a blood draw. Other families are concerned that the lack of risk may create an environment that fosters less vigorous decisionmaking [41]. With the introduction of NIPS, more fetuses with Down syndrome could be identified. Many pregnancies identified as being affected with Down syndrome end in termination, which begs the question What does the future of Down syndrome look like? If more pregnancies affected with Down syndrome are identified and terminated and the condition becomes a medically induced rare disease, there is fear that relatively recent advances, such as the acceptance of individuals with Down syndrome and support services, may disappear [42]. Many families and community members value the perspective that individuals with Down syndrome bring to their lives and question what defines normal [29]. As one mother stated, If we try to make everybody the same, we re going to lose something very basically, fundamentally important to humans [41].

10 112 NAELA Journal Volume 11, Number 2 While there are concerns surrounding the introduction of NIPS into prenatal care, others believe that NIPS is a welcome option to the Down syndrome diagnostic and screening repertoire. More women who are categorized as high risk are electing to proceed with NIPS, and fewer women are electing to proceed with diagnostic testing [43]. With fewer women undergoing diagnostic testing, fewer pregnancies will be lost to miscarriage unnecessarily. The uptake in NIPS could be due to women who want more accurate information regarding Down syndrome but only if no risk is involved. Perhaps many women and families would have found additional information to be useful but refused to proceed with diagnostic testing because it is associated with miscarriage. This could reflect the desire to be prepared for a child with special needs before delivery, using the time to educate themselves and their families on what it means to have a child with Down syndrome, seek out the local chapter of a Down syndrome advocacy group, identify pediatricians and other specialists who have experience with treating those with Down syndrome, or consider adoption options. Many groups in society have differing opinions on whether Down syndrome should be a condition tested and screened for during pregnancy. While it is recommended that all women be offered prenatal diagnostic testing and screening for Down syndrome, it is important to note that the recommendation emphasizes choice. In genetic counseling, genetic counselors realize that the right choice is going to be different for everyone. But as long as there are prenatal testing options designed to identify pregnancies affected with Down syndrome and women have the legal option of terminating their pregnancy, there will continue to be friction between disability advocates and the medical model of offering prenatal testing to every woman. A. Case: Susan IV. Hereditary Cancers Susan is a 32-year-old woman with no personal history of cancer. Susan s mother was diagnosed with cancer in her right breast at age 44 and was later diagnosed with cancer in the left breast at age 59. She died of the disease at the age of 62. Susan is concerned about her breast cancer risk and decides to pursue testing of the BRCA1 and BRCA2 genes. Her test result comes back positive for a mutation in BRCA1, indicating that she has Hereditary Breast and Ovarian Cancer syndrome (HBOC). After consultation with a breast surgeon, she elects to undergo a preventive bilateral mastectomy and plans to have her ovaries surgically removed around the age of Genetics of Hereditary Breast and Ovarian Cancer Syndrome HBOC is caused by mutations in one of two genes, BRCA1 or BRCA2. It is estimated that approximately 5 to 10 percent of cancers are hereditary, meaning that a mutation in the BRCA1, BRCA2, or other genes is being passed down through the family and is causing cancer in the family. Hereditary cancers include common cancers (e.g., breast cancer) diagnosed at a young age, rare cancers (e.g., ovarian cancer, male breast cancer) in a family, and cancers diagnosed multiple times in a family (either in the same person or in multiple family members). NCCN publishes updated guidelines annually that contain specific genetic testing criteria for hereditary cancers [6].

11 Cracking the DNA Code: Genetic Testing Case Examples of Interest Fall 2015 to Elder Law and Special Needs Planning Attorneys 113 Women who have mutations in these genes are at significantly higher risk of developing breast and ovarian cancer than those who do not. These women have an up to 87 percent chance of developing breast cancer, compared with approximately 8 percent in the general population, and an up to 44 percent chance of developing ovarian cancer, compared with less than 1 percent in the general population [44 51]. Because of the high risk of developing cancer, cancer screening for this population is vastly different from that for women at average risk. NCCN guidelines currently recommend breast awareness beginning at age 18, clinical breast exams beginning at 25, annual breast magnetic resonance imaging (MRI) studies beginning at age 25, and the addition of annual mammography beginning at age 30 [6]. Even though screening aims to catch breast cancers when they are small and easily treatable, many women such as Susan choose preventive bilateral mastectomy (the removal of both breasts) to prevent cancer from developing in the first place. While breast reconstruction after mastectomy is common, the decision to undergo screening or preventive surgery is personal and is influenced by many factors. Today, no effective screening is available to detect ovarian cancer at an early stage. In addition, signs and symptoms of ovarian cancer are vague and difficult to recognize, resulting in ovarian cancer usually being diagnosed at a later stage. For these reasons, NCCN guidelines recommend surgical removal of the ovaries and fallopian tubes for high-risk women between the ages of 35 and 40 when they are done having children [6]. Although most of the attention regarding BRCA mutations revolves around women, men with BRCA mutations are also at an elevated risk for breast cancer (up to 8 percent) [52, 53] and prostate cancer (up to 20 percent) [54]. NCCN guidelines for men with a BRCA mutation include breast self-exams, clinical breast exams, consideration of mammograms, and earlier prostate cancer screening [6]. One common myth is that BRCA mutations can only be inherited from mothers. The BRCA genes are inherited in an autosomal dominant manner, which means that they can be inherited from mothers and fathers and passed on to sons and daughters. When a BRCA mutation is identified in a person, his or her first-degree relatives (parents, full siblings, children) have a 50 percent chance of having this mutation. Thus, any children Susan has will have a 50 percent chance of carrying her gene mutation. Family members can consider genetic testing when they are over the age of 18. Because these mutations run in families, more distant relatives are also at risk of carrying them. 2. Previvor Concept BRCA testing became available in 1996, and since that time, the BRCA genes have become some of the most well-known genes among the general population. Genetic testing has led to the identification of a growing number of BRCA mutation carriers. Several patient organizations have been established to help support the men, women, and families facing hereditary cancer. One patient group, Facing Our Risk of Cancer Empowered, or FORCE, helped coin a new term and concept in preventive medicine: previvor [55]. The FORCE website describes this term. Previvors are individuals who are survivors of a pre-disposition to cancer but who haven t had the disease. This group includes people who carry a

12 114 NAELA Journal Volume 11, Number 2 hereditary mutation, a family history of cancer, or some other predisposing factor. The term specifically applies to the portion of our community that has its own unique needs and concerns separate from the general population, but different from those already diagnosed with cancer [55]. FORCE originated the previvor concept in Since then, the term has been adopted by many high-risk women, health care providers, and researchers and was named by Time magazine as one of its top 10 buzzwords of 2007 [55]. 3. Affordable Care Act and BRCA Testing Knowing that a man or woman has a BRCA mutation can be lifesaving information, because the cancer management plan appropriate for him or her varies so dramatically from that of the general population. Family members require special screenings to prevent cancer or diagnose it early. A common misconception is that insurance does not cover genetic testing. Insurance coverage has improved since BRCA testing was first introduced. Although every insurance company is different, if a patient is tested according to NCCN genetic testing guidelines, the patient pays, on average, less than $100 out of pocket for testing [56]. In 2013, BRCA testing was designated as a preventive care service under the Affordable Care Act, thus acknowledging the importance of genetic testing in personalized preventive medicine. This enables unaffected women (those with no personal history of cancer) but whose family history of cancer meets genetic testing recommendations outlined by the U.S. Preventive Task Force to receive BRCA testing with no out-of-pocket cost to the patient [57]. Mary-Claire King, who is credited with localizing the BRCA genes, recently stated, To identify a woman as a carrier only after she develops cancer is a failure of cancer prevention [58]. Increased awareness of hereditary cancers and genetic testing among health care professionals and the public is critical to helping families such as Susan s prevent these cancers. A. Case: Shira V. Alzheimer s Disease Shira is a 25-year-old woman whose maternal grandmother was diagnosed with Alzheimer s disease at age 60 and died from complications related to Alzheimer s at 65. Her maternal grandmother s brother was diagnosed with Alzheimer s disease at age 40 and died from complications from the disease in his late 40s. Shira s maternal aunt (age 50) is starting to show signs of Alzheimer s disease and underwent genetic testing that identified a PSEN1 gene mutation. Shira s mother, who is 48 years old, is currently asymptomatic. Shira is interested in genetic testing for the familial mutation. 1. Brief Genetic Background of Alzheimer s Disease Alzheimer s disease is characterized by progressive, irreversible brain damage that causes memory loss, a loss of global cognitive function, impaired judgment, and can be associated with behavioral and personality changes [59]. In the end stages of this disease, affected individuals are completely dependent on others for fulfilling their basic needs [59]. Approximately 5 million Americans are currently living with Alzheimer s disease [59]. Age is a risk

13 Cracking the DNA Code: Genetic Testing Case Examples of Interest Fall 2015 to Elder Law and Special Needs Planning Attorneys 115 factor for developing Alzheimer s. The risk at age 65 is 3 percent and increases to almost 50 percent in those 85 years and older [60]. Most affected individuals are diagnosed when they are 65 or older (late-onset Alzheimer s disease), but 1 to 2 percent of individuals receive the diagnosis before age 65 (early-onset Alzheimer s disease) [61]. As the baby boomer generation continues to age, the number of people affected by Alzheimer s is expected to increase. Currently, Alzheimer s cannot be prevented or cured and management options are limited [61]. The majority of individuals with Alzheimer s disease (approximately 75 percent) are isolated cases in their families [63]. This is called sporadic Alzheimer s disease. Familial Alzheimer s disease is diagnosed when more than one person in a family is affected, which represents about 25 percent of cases [63]. Less than 5 percent of individuals with Alzheimer s disease present with autosomal dominant inheritance [62], and almost all of these individuals have early-onset Alzheimer s disease [63]. Early onset, autosomal dominant Alzheimer s disease was recently highlighted in the award-winning movie Still Alice. Only three genes are currently known to be causative for Alzheimer s disease: PSEN1, PSEN2, and APP. All three genes are associated with autosomal dominant early-onset Alzheimer s disease. Of the less than 5 percent of individuals who present with this form of Alzheimer s and who have a dominant family history, 45 to 90 percent have a causative mutation identified [63]. For the majority of people who develop Alzheimer s disease, genetic testing will not identify a causative genetic etiology. This is because the more common sporadic late-onset form of Alzheimer s disease is thought to be caused by a complex interaction between genetic and environmental factors [63]. The genetic factors in these cases are called genetic susceptibility genes. In simple terms, if a person has a causative mutation, he or she will develop the disease, but if a person has a genetic susceptibility, his or her risk for developing the disease increases but it is not guaranteed they will actually develop Alzheimer s disease. The mutation identified in Shira s family is a causative mutation, not a susceptibility mutation. There is a susceptibility gene called APOE, which is associated with Alzheimer s disease. This gene is thought to be a factor in multifactorial inheritance, in which both genetics and environment play a role in disease development. Some forms of the APOE gene protect against Alzheimer s disease; other forms are associated with an increased risk for late-onset Alzheimer s [61]. The usefulness of APOE testing for prediction and diagnosis is controversial [64]. In a joint statement, ACMG and the National Society of Genetic Counselors do not recommend genetic testing for Alzheimer s susceptibility genes due to limited clinical utility and the lack of meaningful risk calculations necessary for individual counseling [61]. 2. The Right Test for the Right History As evidenced in the previous case example, family history is a key factor in ordering appropriate testing. A three-generation family history is very useful in determining whether an individual s history is more consistent with sporadic, familial, or autosomal dominant inheritance. From Shira s family history, three factors contributed towards offering genetic testing: (1) early onset of Alzheimer s disease in multiple family members, (2) the identification of a causative mutation, and (3) the patient s interest in presymptomatic genetic testing. Many individuals are familiar with direct-to-consumer testing for Alzheimer s disease through companies such as 23andMe, which Wilcox and Koff describe in their article in this

14 116 NAELA Journal Volume 11, Number 2 issue of NAELA Journal. Direct-to-consumer testing relies on susceptibility genes to provide population-based risk estimates. If Shira were interested in using direct-to-consumer testing to estimate her risk for Alzheimer s disease, she would need to know that such testing does not test for the genetic mutation in her family. With Shira s family history, a result based on testing only her susceptibility genes would be completely misleading. Shira s provider should offer targeted mutation analysis. If she tested positive, Shira will develop Alzheimer s, and if she tested negative, the chance to develop Alzheimer s would return to population chances. Even in the absence of a known mutation, a knowledgeable health care provider would counsel Shira on the risks associated with an autosomal dominant condition based on the family history alone. Ideally, Shira would be referred to a genetic counselor or specialist who could discuss the benefits and limitations of presymptomatic testing of an adult-onset condition with no cure. 3. Informed Consent Presymptomatic genetic testing for adult- and late-onset conditions is not exclusive to Alzheimer s disease and commonly occurs in genetic testing to determine cancer risk (as described earlier in this article). What is unique to Alzheimer s disease is that genetic testing results do not impact surveillance, treatment, or medical management options in a presymptomatic individual. If Shira tests positive for the familial mutation, her provider would only discover that she will develop dementia. Age of onset of Alzheimer s can span 30 years in the same family; therefore, symptoms could appear in Shira as early as her 30s or as late as her mid-60s. Currently, presymptomatic management and treatments for mutation-positive individuals are extremely limited. Outside of limited clinical utility, Shira s results could have implications for other family members, could affect her own mental health, and could impact her plans for the future. If Shira tests positive, we would know that her mother also carries the mutation and will develop Alzheimer s disease. What if her mother declined genetic testing for Alzheimer s and did not want to know whether she carried the mutation or would develop the disease? Does Shira have a history of depression or other mental health disorders? If so, how might a positive result impact her current health? Would a positive result help or hinder her plans for the future? Presymptomatic testing for conditions without a cure and with no management or treatment options occurs in other areas of genetics. Presymptomatic testing for Huntington s disease is a classic example of genetic testing for a noncurable, nontreatable condition. Proceeding with presymptomatic testing for Alzheimer s disease follows the same guidelines that were put in place for Huntington s disease: The individual s decision to proceed with testing is made without coercion, the individual is an adult, and the individual undergoes 1) a neurological exam to rule out early stages of dementia, 2) an evaluation by a mental health specialist, and 3) pretest counseling with a qualified provider [60]. Some individuals find these recommendations excessive, but once the test is performed and the results are available, the information cannot be retracted or withheld. Shira s test results could identify other family members who are carriers; influence her education, career, and reproductive choices; and cause unanticipated emotional and social effects [60]. Shira s test results could have farreaching implications on her future regardless of whether the results are positive or negative. For this reason, consent is emphasized before an individual undergoes presymptomatic test-

15 Cracking the DNA Code: Genetic Testing Case Examples of Interest Fall 2015 to Elder Law and Special Needs Planning Attorneys 117 ing for conditions with limited clinical management options, such as Alzheimer s disease. Informed consent is also required for Alzheimer s disease genetic testing of symptomatic individuals. Similar to individuals with Huntington s disease, it is common for individuals affected by Alzheimer s disease to be symptomatic by the time genetic testing is offered. If necessary, a surrogate decisionmaker for the Alzheimer s patient can be identified through an advance directive [60]. Because genetic testing could reveal the genetic status of the patient s family members, it is critically important for all parties to agree on the testing. Even though genetic testing may not change the person s treatment or management, genetic knowledge could be useful when better treatment options become available. If family members disagree about the utility of genetic testing, other alternatives can be explored, such as DNA banking. DNA banking leaves open the option of genetic testing an affected individual s tissue (usually stored blood) in the future when better genetic tests or treatment options become available. DNA banking also can provide time for families to discuss and decide whether genetic testing for the affected individual is right for the family. 4. Genetic Information Nondiscrimination Act and Insurance Although genetic information is protected, some individuals still have concerns about proceeding with genetic testing, especially if they are presymptomatic. It is important for individuals considering presymptomatic genetic testing to be aware of the protections and limitations of current genetic antidiscrimination laws. The Genetic Information Nondiscrimination Act (GINA), which was passed in 2008, makes it illegal for employers and health insurance providers to discriminate based on an individual s genetic testing results or family health history. There are, however, important exclusions to GINA [65, 66]. GINA does not protect against genetic discrimination when individuals apply for life, disability, or longterm-care insurance [65, 66]. In addition, GINA excludes discrimination protection in certain health insurance plans, such as the plans offered by small employers (those with fewer than 15 employees) [65, 66]. As Alzheimer s disease progresses in an individual, appropriate insurance, advance directives, surrogate decisionmakers, and caretakers become increasingly important. Longterm-care insurance covers services and support to assist with activities of daily living such as eating, dressing, and transferring (e.g., walking). Typically, it is best if long-term-care insurance is purchased well before Alzheimer s symptoms appear or genetic testing occurs. Many long-term-care insurance policies have exclusions for Alzheimer s disease, but if an insurance policy is bought before the manifestation of symptoms, the insurer usually covers the cost of care [67]. Although actual case examples of genetic discrimination involving long-term-care insurance are few and far between, it is nevertheless a concern that if the insurance is not purchased before proceeding with genetic testing, the applicant could be disqualified based on his or her genetic testing results. VI. Conclusion The field of genetic testing is rapidly evolving. As technology continues to improve and the cost of genetic testing declines, individuals will likely have access to an incredible amount of genetic information. Although one can only speculate about the technology that will soon become clinically applicable, newborn screening will likely continue to expand as individual

16 118 NAELA Journal Volume 11, Number 2 states begin to add more genetic conditions to their screening panels. In addition, NIPS will likely evolve to include more genetic conditions. Genetic testing for cancer susceptibility genes such as BRCA1 and BRCA2 has already expanded, as evidenced by the use of multigene panels (testing for multiple cancer susceptibility genes at one time) to replace single syndrome testing (testing for the BRCA genes only). These technological advances are accompanied by a growing awareness of genetic testing in the general population, both of which make it very likely that Elder Law attorneys will work with clients who have experienced genetic testing and/or genetic conditions in some way. Understanding the uses, benefits, and limitations of genetic testing will help Elder Law attorneys support these clients and will become even more important as the genetic testing field continues to evolve. Endnotes 1. Manning, M., and L. Hudgins for the American College of Medical Genetics Professional Practice and Guidelines Committee, Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genetics in Medicine, (11): Schaefer, G.B., and N.J. Mendelsohn for the American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee, Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genetics in Medicine, (5): Shaffer, L.G., on behalf of American College of Medical Genetics Professional Practice and Guidelines Committee, American College of Medical Genetics guideline on the cytogenetic evaluation of the individual with developmental delay or mental retardation. Genetics in Medicine, (9): American College of Obstetricians and Gynecologists, ACOG Practice Bulletin 77: Screening for fetal chromosomal abnormalities. Obstetrics and Gynecology, (1): American Congress of Obstetricians and Gynecologists, American College of Obstetricians and Gynecologists Committee Opinion 486: Update on carrier screening for cystic fibrosis. Reaffirmed 2014; acog.org/resources-and-publications/committee-opinions/committee-on-genetics/update-on-carrier- Screening-for-Cystic-Fibrosis. 6. National Comprehensive Cancer Network, Genetic/familial high-risk assessment: Breast and ovarian. 2014; 7. National Newborn Screening and Genetics Resource Center, National Newborn Screening Status Report American College of Medical Genetics, Genetics evaluation guidelines for the etiologic diagnosis of congenital hearing loss. Genetics in Medicine, (3): Brosco, J.P., and D.B. Paul, The political history of PKU: Reflections of 50 years of newborn screening. Pediatrics, (6): American College of Medical Genetics, Newborn screening ACT sheet: Phenylketonuria National PKU Alliance, About PKU. 2014; U.S. Food and Drug Administration, FDA approves Kuvan for treament of phenylketonuria (PKU). FDA News Release, December 13, 2007; ucm htm. 13. Mitchell, J.J., Phenylalanine hydroxylase deficiency. GeneReviews, last update January 31, 2013; ncbi.nlm.nih.gov/books/nbk Schuett, V.E., What is PKU? National PKU News, last update February 2008; intro.htm. 15. Lavery, S., et al., Successful live birth following preimplantation genetic diagnosis for phenylketonuria in day 3 embryos by specific mutation analysis and elective single embryo transfer. JIMD Reports, : Chorionic villus sampling (CVS) is a prenatal test in which a sample of chorionic villi is removed from the placenta for testing. The chorionic villi shares the genetic makeup of the fetus.

17 Cracking the DNA Code: Genetic Testing Case Examples of Interest Fall 2015 to Elder Law and Special Needs Planning Attorneys Amniocentesis is a procedure in which amniotic fluid is removed from the uterus for testing. Amniotic fluid is the fluid that surrounds and protects the fetus during pregnancy. This fluid contains fetal cells and various chemicals produced by the fetus. 18. American College of Medical Genetics, Newborn screening ACT sheet: Congenital hearing loss National Institutes of Health, Early identification of hearing impairment in infants and young children. NIH Consensus Statement, March 1 3, (1): U.S. Preventive Services Task Force, Universal screening for hearing loss in newborns: US Preventive Services Task Force recommendation statement. Pediatrics, (1): American College of Medical Genetics, Statement of the American College of Medical Genetics on universal newborn screening Yoshinaga-Itano, C., et al., Language of early- and later-identified children with hearing loss. Pediatrics, (5): Moeller, M., Early inervention and lanuage development in children who are deaf and hard of hearing. Pediatrics, (3): E Lane, H., Ethnicity, ethics, and the deaf-world. Journal of Deaf Studies and Deaf Education, (3): National Institute on Deafness and Other Communication Disorders, Cochlear implants. Statistics updated November 2013, partial update August 2014; National Association of the Deaf, Cochlear implants: NAD position statement on cochlear implants. 2000; Women who are considered high risk are those who over 35 years of age at delivery, have a positive maternal serum screening result (i.e., first trimester screen, quad screen, sequential screen), have ultrasound findings that indicate that the fetus could have Down syndrome, and have a family history Down syndrome. 28. National Down Syndrome Society, Down syndrome facts. 2012; Down-Syndrome-Facts. 29. Berube, M., Life as We Know It. 1996, New York City: Pantheon Books. 30. American College of Obstetrics and Gynecology, ACOG Committee Opinion No. 469, Carrier Screening for Fragile X Syndrome. Obstetrics and Gynecology, (4): Wright, D., Downs: The history of disability. 2011, Oxford: Oxford University Press. 32. Pergament, D., and K. Ilijic, The legal past, present and future of prenatal genetic testing: Professional liability and other legal challenges affecting patient access to services. Journal of Clinical Medicine, (4): Garcia, G. A challenge to the delivery of genetic services: Liability for negligent delivery of reproductive services. Washington State Department of Health Genetic Services Policy Project. Accessed July 11, 2015; depts.washington.edu/genpol/docs/garcialiability.pdf. 34. Becker v. Schwartz, 400 N.Y.S.2d 119 (1977). 35. Haymon v. Wilkerson, 535 A.2d 880 (1987). 36. American College of Obstetricians and Gynecologists, Technical Bulletin 38: Antenatal diagnosis of genetic disorders. American Journal of Obstetrics and Gynecology, American College of Obstetricians and Gynecologists, Committee Opinion 545: Noninvasive prenatal testing for fetal aneuploidy. American Journal of Obstetrics and Gynecology, (6): Dahl, K., et al., Informed consent: Attitudes, knowledge and information concerning prenatal examinations. Acta Obstetricia et Gynecologica Scandinavica, (12): Tischler, R., et al., Noninvasive prenatal diagnosis: Pregnant women s interest and expected uptake. Prenatal Diagnosis, (13): Suter, S.M., The routinization of prenatal testing. American Journal of Law and Medicine, (2&3): Scott, L., Is this the beginning of the end for Down syndrome? The Courier-Mail, March 17, Rochman, B., Early decision: Will new advances in prenatal testing shrink the ranks of babies with Down syndrome? Time, February 27, Chetty, S., M. Garabedian, and M. Norton, Uptake of noninvasive prenatal testing (NIPT) in women following positive aneuploidy screening. Prenatal Diagnosis, (6): Ford, D., et al., Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet, 1994.

18 120 NAELA Journal Volume 11, Number 2 19(343): Struewing, J.P., et al., The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. New England Journal of Medicine, (20): Antoniou, A., et al., Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: A combined analysis of 22 studies. American Journal of Human Genetics, (5): Easton, D.F., D. Ford, and D.T. Bishop, Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. American Journal of Human Genetics, (1): King, M.C., J.H. Marks, and J.B. Mandell, Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science, (5645): Narod, S., and K. Offit, Prevention and management of hereditary breast cancer. Journal of Clinical Oncology, (8): Whittemore, A.S., G. Gong, and J. Itnyre, Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: Results from three U.S. population-based case-control studies of ovarian cancer. American Journal of Human Genetics, (3): Ford, D., et al., Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. American Journal of Human Genetics, (3): p Tai, Y.C., et al., Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. Journal of the National Cancer Institute, (23): Thompson, D., D. Easton, and Breast Cancer Linkage Consortium, Variation in cancer risks, by mutation position, in BRCA2 mutation carriers. American Journal of Human Genetics, (2): Breast Cancer Linkage Consortium, Cancer risks in BRCA2 mutation carriers. Journal of the National Cancer Institute, (15): p FORCE Facing Our Risk of Cancer Empowered. What is a previvor? Accessed July 11, 2015; MYRIADPRO, Insurance company information. 2015; insurance-company-information. 57. MYRIAD. BRCA testing granted preventive care designation under the Affordable Care Act. March 6, 2013; investor.myriad.com/releasedetail.cfm?releaseid= King, M.C., E. Levy-Lahad, and A. Lahad, Population-based screening for BRCA1 and BRCA2: 2014 Lasker Award. Journal of the American Medical Association, (11): alz.org Alzheimer s Association, What is Alzheimer s? 2015; is_alzheimers.asp. 60. Hedera, P., Ethical principles and pitfalls of genetic testing for dementia. Journal of Geriatric Psychiatry and Neurology, (4): Goldman, J.S., et al., Genetic counseling and testing for Alzheimer disease: Joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genetics in Medicine, (6): Autosomal dominant inheritance occurs when a mutation in one gene is sufficient to cause changes in development. If a parent has an autosomal dominant condition, there is a 50 percent chance that his or her children will also inherit the condition. 63. Bird, T.D., Alzheimer disease overview. GeneReviews, last revision April 3, 2014; gov/books/nbk AGS Ethics Committee, Genetic testing for late-onset Alzheimer s Disease. Journal of the American Geriatrics Society, (2): Payne, P.W., et al., Health insurance and the Genetic Information Nondiscrimination Act of 2008: Implications for public health policy and practice. Public Health Reports, (2): Genetic Alliance, Genetics and Public Policy Center at Johns Hopkins University, and National Coalition for Health Professional Education in Genetics, GINA & You: Understanding GINA, the Genetic Information Nondiscrimination Act of May 2010; LongTermCare.gov, U.S. Department of Health and Human Services, Administration on Aging. The Basics. Accessed July 11, 2015;