"Ethical Controversies in Genetic Testing" by Bonnie Arzuaga for OPENPediatrics

ethical controversies in genetic testing by dr. Bonnie are swagga hello my name is dr. Bonnie ARS Vega and today I'll be talking about the ethics of genetic testing in infants and children introduction some learning objectives for today there are 5-1 to describe four basic ethical controversies surrounding genetic testing of pediatric patients 2 to define the best interest standard and to demonstrate how it can be applied to genetic testing of pediatric patients 3 to compare and contrast predictive testing for carrier States with predictive testing for actual phenotypic disease 4 to list 3 characteristics that make a disease a good candidate for newborn screening and 5 to identify ways that expansion of the newborn screening program may lead to ethical controversy a little bit of background information about genetic testing in the year 2000 the Human Genome Project was completed and this has made it increasingly possible to test for specific genetic conditions at all stages of a patient's life and actually since then genetic testing for patients has become increasingly popular in the hospital and also in outpatient settings however the implementation of genetic testing is ethically complex and this is especially true with testing of pediatric patients and this is mainly because a their legally incompetent meaning that they cannot legally make their own medical decisions but they have to have a surrogate decision maker which is usually their parents but can sometimes be a guardian the implementation of newborn screening programs throughout the United States has made it possible for clinicians to conduct population level genetic screening however there's a lack of knowledge about the correlation of many genotypes and disease expression for many conditions that we now test for therefore many unaffected patients will be flagged leading to anxiety confusion and sometimes even over treatment so some questions for consideration when we talk about genetic testing the first one is what if any are the ethical concerns regarding the newborn screening program and also of genetic testing in general should disorders with a variety of presentations some of which may not have successful treatments be included in newborn screening programs in order to detect those few cases with the most severe and potentially treatable forms should parents be able to request genetic testing which may indicate that their child is a carrier for conditioned or to have a condition that is of adult-onset in nature so in order to highlight some of these questions and some of the problems that we face but to talk about a hypothetical case so this is a case of baby Amelia so baby Amelia is boring full-term following no prenatal complications she does well in the newborn nursery and she's discharged home with her parents however her newborn screen returns one week later with positive findings for a crib a disease her pediatrician cannot interpret these results for her parents and therefore refers them to a pediatric neurologist so a little bit about CREB a for those who aren't familiar with the disease it's an autosomal recessive lysosomal disorder and has an incidence about one in a hundred thousand births in the United States and it affects the white matter of the central and peripheral nervous systems most patients present within the first six months of life with what is known as infantile disease which manifests as extreme irritability spasticity and developmental delay from there there is severe motor and mental deterioration often leading to death by the age of two however ten to fifteen percent of patients with car bay have a later onset commonly differentiated as either late infantile juvenile and adult onset forms the later onset forms have less disease severity and a slower progression these patients can be clinically normal until weakness vision loss and intellectual regression become evident and those with adult onset may have spastic paraparesis as the only symptom and may live relatively normal lives prior to being diagnosed one of the oldest patients ever diagnosed with the adult onset form of this disease was an 84 year old woman disease severity is variable even within families so going back to baby Amelia her parents bring her to the neurologist and the neurologist explains to her family that the infant's DNA test indicated that she's most likely a carrier for the disease but that further testing is required however the follow-up testing on baby Amelia only provides ambiguous results so why is this well newborn screening and genetic testing for this condition in particular cannot differentiate between the infantile juvenile and adult onset forms additionally it cannot tell whether a patient will be severely or mildly affected so the symptoms of early infantile onset of CREB a typically include irritability feeding difficulties episodes of fever without any sign of infection a stiff posture and slowed mental and physical development so now imagine that your baby Amelia's parents as we know infants can sometimes be irritable sometimes not eat well have unexplained fevers or even delayed developmental milestones for benign or unknown reasons however now that Amelia has had this testing done her parents will likely be hyper vigilant and anxious about any aspect of her health and well-being that is not perfect so even if Amelia does not have the infantile form of this disease she will likely undergo more invasive and expensive testing if her parents have any concerns that otherwise would not normally raise any red flags controversies so what are some of the basic ethical controversy surrounding genetic testing and we're going to talk about four in detail the first one is that genetic information gathered from testing may have limited predictive power and that's because possessing a gene does not always equate to having a specific phenotypic condition one example of this is possessing the brca1 or bracha one unko gene possessing this gene does not guarantee that a particular patient will develop the clinical diseases of cancer however despite this new technologies in pre-implantation genetic diagnosis have recently gained popularity through IVF techniques parents can choose to implant and gestate embryos which do not possess the bracha one gene or other identifiable quote undesirable genes going back to our case so Amelia happens to have an 18 month old brother who's named Benjamin he was born in a state that does not provide crab a testing on their newborn screening panel Benjamin currently displays no symptoms of the disorder however now his parents want to know if they should have him tested for this disease also so the case of Benjamin brings us to our second controversy which is that information gathered is familial meaning that results of one patient's tests are applicable to that person's parents their siblings and also their offspring siblings of the affected individual may not want to know their potential genetic destiny and they may inadvertently discover it through testing of their sister or brother siblings who are unaffected may also suffer from forms of survivor guilt and this has been shown in at least a few studies the third problem is that paternity may sometimes come into question if one parent is a carrier for a condition and the other parent is not then there may be a question about who is actually the father of the child going back to Amelia so the neurologist tells her parents that it's possible that Amelia may develop CREB a at some point in the future but he cannot say for certain you can also not predict when it may happen if there is any way to prevent it or if there will be a viable treatment option so this brings us to our third controversy which is that the risks of genetic testing may not be easily or immediately appreciable as a tend to be psychological financial or social psychological risks occur not only with the patient who is has the disease but can also affect the patient's family and specifically in Pediatrics the patient's parents who because of the hereditary nature of genetic disorders can experience anxiety guilt and sometimes impaired self-esteem there are also social and financial risks such as exclusion from sports or other activities and we see this sometimes in children who are carrier States for sickle-cell disease for example may be excluded from team sports in high school patients may also have difficulty in obtaining insurances such as health insurance life insurance or disability insurance and there's also potential for employment discrimination especially if it's known that a patient possesses a gene for a disease that will make them unable to work effectively within the next few years the fourth controversy is that many genetic conditions are difficult to treat or prevent and this brings into question the clinical value of testing for them at all so on the one hand if an adult patient requests a genetic test we know that in general adult patients have the right to know their genotypic information even if that condition may not be treatable or preventable however the right for a parent to know information pertaining to the conditions that are either untreatable or unpreventable or may not even have clinical onset until adolescence or adulthood is debatable the older child or adolescent who may possess some decisional capacity may not wish to know whether they are destined to have a particular untreatable disease or they may not wish for their parents to know best interest standard so this brings us now to the best interest standard which is a basic ethical standard that we usually talk about when we talk about ethical dilemmas in general so the definition of the best interest standard varies in the traditional medical ethics texts in the United States but in general it says that parents are given the right to make decisions for their children under a best interest standard and this means that they're not required to make the best decision possible only one that is at the very least neither abusive nor neglectful by utilizing a basic standard of reasonable and this decisions therefore should reflect what is most reasonable to most people and what most people would choose for themselves in similar circumstances so here is a pretty simple example imagine that it is January and it's snowing outside and you are on maternity leave with a new infant and you really really really want a cup of coffee and you have no coffee in your house so you put your infant in a snow suit you put them in his car seat and you drive to get your morning coffee this is technically not in the best interest of the infant but no one would arrest you for doing this type of thing so if the best interest standard is considered to be the primary guiding principle for pediatric decision making then how can it be applied to predictive genetic testing and children predictive genetic testing so what is the American Academy of Pediatrics say about this well first they say that genetic testing is best offered in the context of genetic counseling and that all decisions about whether to offer testing should be driven by the best interest of the child – they say that health care providers should inform families about potential familial implications prior to testing and encourage them to share the information with their extended family or refer them to genetic counseling so there are some problems that arise when these first two recommendations are not followed first there's a lack of knowledge from general pediatricians about very rare diseases and so sometimes the pediatrician may not be able to provide adequate counseling to a family about a particular disease state there is also a lack of access to specialists in many areas of the country and so even if a pediatrician is able to give a family proper counseling there may not be able to follow up with a specialist and gain adequate treatment for their child the third recommendation from the American Academy of Pediatrics is that assent of the older child for testing when appropriate is encouraged although the final authority lies on his or her parents or guardians finally the use of any direct-to-consumer testing is strongly discouraged due to the lack of test oversight and appropriate counseling for those of you who aren't familiar with direct-to-consumer testing it is essentially a service that people can purchase in which they send a DNA sample to a company usually via a buccal swab and the company will run their DNA identify any mutations and send them back a report however directory consumer testing excludes allowing families to talk about getting the testing or to encourage them to share their results with the rest of their family consumers can also misinterpret results or demand further unnecessary testing from their physician after getting direct-to-consumer results without appropriate counseling but I want to talk about one more scenario what if parents request that their infant or child be tested in order to identify a carrier status just like baby Amelia's parents did in the case of her brother Benjamin so here we have to ask ourselves four questions how does differ from testing for actual phenotypic disease well on the one hand a carrier status really has no clinical significance if anything it may have significance for when a patient decides to have children of their own – if a carrier state imparts some phenotypic effect but not the full phenotype is that different so here we can consider for example fragile X syndrome in women so fragile X syndrome is essentially a syndrome in which there are a triplet repeat on the X chromosome the more repeats that you have the more neurologically impaired you are and the more severe your phenotype women who are carriers of fragile X maybe variably affected depending on how many repeats they have on their one x chromosome the third question is what if the carrier state imparts a protective effect for example if you're a sickle cell carrier in which case you have some protection against malaria therefore if you're planning a trip to Africa or going to move to Africa you would be less at risk for actually getting malaria so it may be useful to know that information and the fourth question is what if parents are requesting to test for a carrier status in the sibling of a child either identified as a carrier themselves or affected by the disease so what are our professional institutions say about the potential answers for these questions well the American Academy of Pediatrics the American College of medical genetics and the Institute of Medicine all recommend against determining a child's carrier status the AAP and the ACMG also go so far as advising against school-based testing or screening programs in the schools which presently is not widely done at least in this country so school based testing aside then what is the significance for other screening programs in particular the expansion of the newborn screening program newborn screening program while the Institute of Medicine has suggested that three criteria must be filled in order for any population-based screening program to be effective the first is that there must be a clear indication of benefit to the newborn – there must be a system in place to confirm a diagnosis once a newborn is flagged and 3 there must be treatment and follow-up available to any affected newborn so then with this in mind how do we decide what diseases should be included in the newborn screening program and as you may be well aware the newborn screening program started in the mid 20th century with PKU which is a disease that if infants or children ingest female alanine it can actually cause neurodevelopmental delay however if they avoid any food products with phenyl alanine in them they can be neurologically spared so since the 1970s newborn screening has expanded to include over 50 diseases the newborn screening is available in every state there is a core list of diseases that are federally mandated but besides that corylus states are basically able to decide which diseases in which conditions they're going to include on their screening panels so in order to be a candidate for newborn screening a condition should be an important health problem to find either by the prevalence of the condition in the state or about the consequences of the disease on the individual there should be a recognized treatment for patients as well as a benefit to early detection and there should be a suitable test for the condition which is easily performed on a large scale and has no false negatives and very few false positives so with this what we see in newborn screening programs is that tests that are done within these panels have a very high sensitivity however they have a low specificity and so sometimes you can get many false positives and this is accentuated in babies who are born prematurely for example and so babies will be flagged for having rare conditions often metabolic conditions that when further testing is done it is determined that they actually do not have these conditions at all so with this in mind we should think about mandatory newborn screening there are very few states in the United States where newborns are mandated to have screening however in the vast majority of states newborns are screened without necessarily asking their parents about it first parents have a right to opt out of testing if they don't want it however most parents actually don't even realize that their babies will be screened when they're in the hospital prior to discharge and therefore parents have to be savvy and know that this is going to happen in order to opt out of it before it happens so with that what if any are the ethical concerns regarding newborn screening program and genetic testing in general should disorders with a variety of presentations some of which may not have successful treatments be included in the newborn screening program in order to detect those few cases with the most severe and potentially treatable forms should parents be able to request genetic testing which may indicate their child's be a carrier for a condition or to have a condition that is adult onset in nature summary so I know I've brought up a lot of questions today not very many answers and that's really because we don't at this Junction have very many answers genetic testing as I said in the beginning is widely done newborn screening programs are available in every state the vast majority of newborns get screened and the consequences of that screening can sometimes be severe even if a patient doesn't necessarily have the condition that has been flagged as positive so we must carefully consider the complexity of these issues prior to testing being offered to any family or any patient any testing that is done should be preceded by detailed counseling informed consent and careful attention to confidentiality the addition of new conditions to newborn screens should be carefully scrutinized prior to widespread incorporation of testing and the ethical principle of beneficence which means doing good for the affected patients should be balanced by the principle of non-maleficence avoiding harm to non affected patients before considering actually doing any genetic testing on a patient thank you very much for watching I hope you learned something today and more importantly I hope that this presentation brought up more questions for you to consider as you go about your clinical care of newborn infants please help us improve the content by providing us with some feedback you

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