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Q: You mention in your blog posts that not every state screens for the same conditions. Why is this the case? When my baby is born, how can I make sure that she is screened for everything?
Summer Cox says, Each state screens for a different number of conditions. You can find out about the conditions screened in your state at the Baby’s First Test site (http://www.babysfirsttest.org/newborn-screening/states). The Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children works with the US Secretary of Health and Human Services to develop newborn screening guidelines. Currently, the group recommends screening for 31 conditions, including hearing loss and critical congenital heart disease. The majority of states screen for at least 29 conditions. The differences among what states offer are due to laws, funding, financial costs and availability of tests and treatment.
If you want your baby to be screened for a condition that is not done in your state, there are several private companies and universities provide these services at an additional cost (http://www.babysfirsttest.org/newborn-screening/conditions#2). Generally, these services are not covered health insurance plans, but it is always good to check first.
More information about newborn screening can be found at the Association of Public Health Laboratories website: http://www.aphl.org/aphlprograms/newborn-screening-and-genetics/50th-Anniversary-of-Newborn-Screening/Pages/What-is-Newborn-Screening.aspx.
Q: My husband and I are interested in having a home birth. How can we be sure that our child will receive newborn screening if we don't deliver at a hospital?
Summer Cox says, In Oregon, and I believe in most states, the birthing practitioner is responsible for collecting the newborn screening specimen. That requires the midwife or non-hospital practitioner to make sure the newborn screening specimen(s) is/are drawn according to the appropriate state laws.
As new parents you can also be pro-active by inquiring whether the specimen has been drawn. If your midwife or doula cannot perform the test, you should bring the baby to a hospital within the first 24-48 hours of life to have the test done there.
More information about newborn screening can be found at:
- Association of Public Health Laboratories website:http://www.aphl.org/aphlprograms/newborn-screening-and-genetics/50th-Anniversary-of-Newborn-Screening/Pages/What-is-Newborn-Screening.aspx
- Baby’s First Test: http://www.babysfirsttest.org/
Q: What do you recommend that parents do when they have a suspicion or concern that their child's developmental delays or disabilities are due to a genetic condition? If a primary care provider is unconvinced that screening is necessary, what should a parent's course of action be?
Howard Levy says, As a geneticist, my first response to this question is that everything is genetic, to some degree. Even getting hit by a car is genetic. Granted, the major risk factor for getting hit by a car is being in the middle of the road when a car is coming, but there are clearly genetic factors that predispose to risk-taking behavior (that might cause someone to hang out in the middle of the street), as well as genetic factors that might make it harder to quickly move out of the way of a car or even recognize that a car is coming (e.g. poor vision or poor hearing).
You are correct in your implication that developmental delays and disabilities often (but not always) have significant underlying genetic causes. The relevant questions are to what degree genetic factors are contributing to a child’s problems and to what degree knowledge of those genetic factors might help in managing those problems.
As a primary care physician, my goal is to help my patients understand what is going on and what can (and can’t) be done about it. Tests and consultations are often appropriate, but sometimes it is my job to explain that we (think we) know with a high degree of certainty what is going on and that additional evaluation is not appropriate.
Ultimately, however, it is neither the geneticist’s nor the primary care provider’s job to make the final decision. We are consultants and advisors. Patients (and parents) are the consumers of our services, and are the ones whose opinions matter most. If you feel that further genetic evaluation is appropriate, you owe it to yourself and your child to pursue that question further. That might mean a heart-to-heart conversation with the primary care provider to understand why s/he doesn’t agree, or it might mean taking further action yourself.
I don’t recommend trying to pursue direct-to-consumer testing or screening—without extensive knowledge and experience it is very easy to get in over your head and do more harm than good. And genome sequencing is almost certainly not the appropriate first step. However, a consultation with a geneticist would likely be of great value in determining if there are any appropriate tests or evaluations to pursue.
If your insurance doesn’t require referrals to see a specialist, you need only identify a geneticist in your region and call to make an appointment. I recommend the American College of Medical Genetics and Genomics genetics services search engine, available at https://www.acmg.net/ACMG/Find_Genetic_Services/ACMG/ISGweb/FindaGeneticService.aspx?hkey=720856ab-a827-42fb-a788-b618b15079f9. If you do need a referral, then you should ask for it during that honest conversation with the primary care provider. Rarely, it may be necessary to find a new primary provider or even a different health insurance plan, but hopefully such drastic measures can be avoided.
Julie Rousseau says, Today we know that there are multiple genetic and non-genetic causes of intellectual disabilities and developmental delays. Exploring the possibility of a genetic cause can be important not only to understand the origin, but to guide care as many genetic conditions are associated with subsequent health risks in addition to the developmental component. If your primary care provider is not well versed in this area, we might suggest that you may request referral to a provider more familiar with this evaluation, such as a geneticist, neurologist, or a developmental pediatrician. These health care providers can then follow established practice guidelines for the evaluation of children with ID/DD that can be used to support your request for genetic screening.
Q: My 2 yr old son has a platelet disorder. He has enough platelets but they don't work as well as they should so when he has a large bleed or a head injury he needs a platelet transfusion. Our children's hospital has done all of the testing they can and could not find the cause of the platelet disfunction. My question is whether genetic testing would help treat my son's condition. To put it another way, is there a known genetic disorder that has this symptom that would cause us to alter our care or would we do the same thing regardless of the test results.
Howard Levy says, Almost any medical problem can sometimes be due to an underlying genetic cause. In this case, I'm referring to variations or mutations in a single gene causing the problem, rather than the fact that there is always some degree of genetic variation contributing to the likelihood of developing a problem or the severity of that problem.
There are definitely some known genetic conditions that can cause someone to have normal amounts of platelets but abnormal platelet function. And sometimes knowing the underlying cause of the problem can help to determine the best course of treatment.
Either or both of a hematologist and/or a geneticist may be able to help answer this question specifically. Naturally, there will be variation in the knowledge that any one specialist has: some hematologists know a lot more genetics than others and some geneticists know a lot more hematology than others. If the specialist(s) that you have consulted so far haven't been able to figure this out, then I would look for additional opinions. Assuming that you've spoken to a hematologist but not a geneticist, your next logical step might be to request a genetics consultation. Or, you might opt for a second opinion from another hematologist.
Thinking more generally, no matter what organ system a patient has problems with, the same principle applies. If you suspect or wonder about an underlying genetic cause, I would consider either or both of a genetics consultation or an opinion from someone who specializes in the diseased organ system but has some knowledge and experience with genetic causes of disease.
Q: We talk about the costs of the sequencing and how those costs are coming down. What are the strategies going forward to dealing with the enormous amounts of data from whole gene sequencing and the associated costs with the data analysis?
Howard Levy says, What an excellent question! The amount of data generated from a single genome sequence is huge: there are approximately 6 billion nucleotides (“genetic letters”) contained in the two copies of the genome within each of our cells. And in some cases it makes sense to sequence one person’s genome multiple times, for example when new technology brings improved accuracy or to monitor changes in cells as a patient undergoes treatment for cancer.
Understanding what the genome means is a challenging problem. Sometimes we think we know for sure that a variant is (always) harmless or (always) causes disease. Most of the time individual variants haven’t been reported and studied enough to know their significance. In those cases, we use multiple prediction tools to make our best guess. And, as we collect more information, a lot of what we think we know today will likely change.
The field of bioinformatics specializes in processing all of this data and making sense of it. Part of the solution will come gradually over time, as more people’s genomes get sequenced and we learn more about what each specific variant does (and doesn’t!) mean. There are many medical centers, private companies and individuals working on this problem. I have faith that these brilliant and innovate people will come up with disruptive breakthroughs that change the landscape and improve the efficiency and accuracy of genomic analysis.
Julie Rousseau says, As you mention, now that the cost of genome sequencing itself has dropped, data analysis is quickly being recognized as the rate-limiting factor to help health care providers and patients benefit from this information. This is key especially when you consider both the time involved and the associated expenses. Reducing our time and expense relies on using software tools to filter through the sequence data in such a way that the genome variants presented to the individual performing the analysis are few in number and provide the highest value in predicted, or known, significance. In order for these tools to be effective, the databases holding all the genome variants and thus underlying such analyses must be complete and well curated.
To accomplish this new area of variant sciences, there is growing emphasis on collaboration to capture genome variant data across multiple populations in a consistent manner so that factors such as allele frequency and phenotype are able to be incorporated more thoughtfully. Which variants are included in a filtered list and how the underlying databases are used will depend on the question being asked by the provider or researcher. Importantly, identifying the causative variant for an individual with a rare Mendelian disease will follow a different logic from one in which you are determining the multiple risk alleles associated with a common complex disease. Therefore, the tools available for us to use must be powerful enough to capture and manipulate large volumes of data, while being flexible enough to accommodate the different biological logic we are using to address different questions.
Spending much time now working with health care providers and their patients, we are confident that current efforts to enhance our understanding of genomic variation will result in the benefit of new knowledge for patients that we all seek.
Tina Hambuch says, As has been widely publicized, the costs of sequencing have plummeted in such a way that it has defied Moore’s Law. However, the benefits of these improvements haven’t necessarily seemed obvious to people seeking genetic testing. There are a few reasons for why that is the case. First, the sequencing technologies have become more efficient, but only at sequencing very large amounts of DNA- it’s a “bulk” discount. So, sequencing an exome is now comparable to what it costs to sequence a single gene using a different technology, but it is still expensive. More importantly, we still need genetics experts to figure out what the biological and clinical implications of the information within a genome are for an individual patient. As the amount of genetic information increases, this expense increases, so even as the expense for the technology decline, we still have significant challenges with saying what that genetic information means. If we are talking about a whole genome, there is a lot of information that can help to answer many possible questions. It is not feasible to address all of them at once, so most people evaluate the information in the genome based on the specific clinical question for which the test is ordered. The great thing about a genome is that if you have a different question in two years, you can go back and ask that one at that time and it is only the cost of re-analyzing the data. There are many efforts under way to increase databases and increase the quality of the information foundwithin databases. Currently, there are many databases and publications, but the quality and quantity of evidence is highly variable. If that evidence is going to be used to make medical decisions, needs rigorous and careful evaluation by a clinical expert. Hopefully, standardization and improvement of databases will rapidly improve such that the job of the experts will become much easier, and this will drive down costs.
Q: Our child, myself and my husband have gone through whole genome sequencing and have the result and are in need of further information as not much is currently known about the mutation (or is not in literature that can be accessed) in the gene that was found. We would like to connect to researchers worldwide who are currently working on the gene for more information. It is likely the causal gene in our child's condition (from what is known about the gene). How do we do that?
Julie Rousseau says, You and your family have taken a very important and informed approach to inquire about the potential role that genetics might play in diagnosing your child’s condition, and in looking for researchers who might be able to help you find out more. Discoveries made about rare diseases depend on participation in research by interested families like yours. There are a few ways to find the experts who can help:
- If your child’s condition falls into a category of known disorders that is represented by a patient advocacy group, those groups typically know the researchers and clinicians in the field who can provide more information and help you find a research study. The Genetic Alliance is a great place to start.
- Talk with a physician or a genetic counselor at a nearby pediatric research hospital. If you live in the northeast, Boston Children’s has a center that focuses on the study and treatment of rare diseases (http://www.childrenshospital.org/mantoncenter), and can connect you to relevant research initiatives at the hospital.
- Speak with your provider who ordered the test, who may then go back to the lab that performed it for more information about the genetic mutation which was identified. Labs databases are large and they would be able to tell you if they have seen the mutation before. They may also be able to keep you updated if more information emerges about the mutation.
- Find the researchers who are publishing regularly on the gene of interest or disease condition by doing a search in the literature (http://www.ncbi.nlm.nih.gov/pubmed/). You can definitely reach out to the researcher directly, they love hearing from families.
Q: My husband and I adopted a baby girl several years ago. We know little about her birth parents, but can our family health history have an effect on her? My husband struggles with alcohol abuse and has been in and out of rehab programs. His father struggled with a similar problems with alcohol. I know that children of alcoholics often have trouble with addiction as well, but do my husband's difficulty with addiction put my daughter at risk of alcoholism? Or will she be alright because she is not a blood relative?
See next question for answer.
Q: My wife and I adopted a son as a baby. He was taken away from his parents because of their difficulties with substance abuse. My wife and I drink alcohol only occasionally and always in moderation, and we have no family history of substance abuse. Is is still likely that my son will have the same struggles with addiction and substance abuse as his biological parents?
Steven Bleyl says: Both of these are good questions, and they illustrate the notion that more than genetic information is required to accurately predict the risk of some conditions, in this case addiction. Complex conditions such as alcoholism result not only from our genetic makeup, but also from the environment in which we were raised. How much of each has long been argued in the so called "nature versus nurture" debate. In the first case,an adopted child brought into a home where struggles over addiction are present may be at some risk for similar addiction herself. Alternatively, in the second instance a child with biologic family history of substance abuse would also be at some future risk despite his newsubstance-abuse-free environment. The exact degree of risk for the children in each of these instances is not a simple calculation. However,acknowledging that these risks exist and taking steps to mitigate them is the important step.
Q: Why should I bother taking a family health history when I can just have my DNA tested? Wouldn't that be more accurate anyway?
Steven Bleyl says: Although technology for sequencing one’s genes has advanced at a staggering pace over the last 10 years, most of these advances have been in the realm of sequence generation rather than any area of sequence interpretation. While it is possible to obtain a "whole genome sequence" for yourself, our ability to interpret that sequence and accurately predict your risk for any given condition is still very limited. This is particularly true for complex genetic condition such as diabetes or coronary artery disease, where a thorough family history is still far and away a better predictor of one's risk.
Q: I am concerned that collecting a family health history will do more harm than good. What if I learn about a condition that can't be prevented? If I eat right and exercise without taking a family health history, isn't that good enough?
Steven Bleyl says: This concern is usually raised in relation to genetic testing, rather than in discussing one's family history (which is usually known to the person). However, the discussion of "unanticipated results" often arises in any discussion of genetic counseling or genetic testing. The potential harm that lies in identifying risk for a condition for which there is no treatment or prevention measures is inherent in both family history reviewed and genetic testing. However this harm must be weighed against potential benefits to an individual in identifying conditions for which a treatment or preventive strategy has been demonstrated. While I would never discount the benefits of a healthy diet and exercise, there are examples where certain risk factors identified through family history can be life saving. For example, a family history of multiple individualswho died suddenly from aortic rupture could uncover a genetic predisposition called thoracic abdominal aortic aneurysm and dissection (TAAD), a condition where genetic testing and/or medical screening could identify the need for medication and perhaps surgery to mitigate risk in an otherwise healthy appearing individual.
Q: If my family health history is so important to my health, how can I protect my privacy? Can my employer ask for my family health history? Will my doctor keep it private like the rest of my medical record?
Steven Bleyl says: As the name suggest, the Genetic Information Nondiscrimination Act of 2008 (GINA) protects against discrimination based on genetic information, including family history information, for both health insurance and employment. Your doctor is required to protect this information in the same ways they protect the rest of your personal health information. Actually the protections against discrimination granted to genetic information and family history in GINA has been uniquely strong when compared to other medical history. Although this has recently changed under the Affordable Care Act, pre-existing conditions (besides genetics) have long been fair game to health insurance companies as areason to deny coverage. GINA does not prevent family and genetic history from being used in decisions for some types of insurance (life and disability insurance for example), but this is true for all types of medical history.
Q: If my grandmother had breast cancer, but tested negative for BRCA mutations, is it still relevant to my family health history
Dana Zakalik says: Yes, it still is relevant, especially if your grandmother was young when she was diagnosed, or if there are other cancers in your family. Family history matters even in the absence of a known mutation in BRCA 1/2. Also, while BRCA 1/2 are the most well known mutations, there may be other genes associated with a family history of breast cancer and related to increased risk.
Q: I have tried in the past to get my family to talk about family health history, but my family members insist they don't want to know anything about their genetics. They say that knowing what diseases they're going to get will only give them anxiety. How can I explain that knowledgeand preventive measures can improve their health? Are there any good resources available to get the family talking?
Penelope Moore says: People are often responsive to stories that illustrate the power of knowledge associated with family health history. For example, I have a close friend whose father and uncle died of heart disease in their early 50s and 60s respectively. My friend also had a wake-up call when he had a first heartattack at the age of 47. This wake-up call along with the sudden and traumatic deaths of his father and uncle prompted him to make radical lifestyle changes, which he often talks about with others. My friend’s story is inspirational to others who have witnessed the benefits of the changes he has made andhow his quality of life has improved as a result. By sharing his story, he has influenced others to be more proactive about health concerns in general and has enabled them to consider the link between health concerns and their family health history. The Does It Run in The Family toolkit developed by Genetic Alliance in collaboration with community partners nation-wide is a free and excellent resource designed specifically to facilitate conversations about family history within families and/ or community groups. This tool is also recommended because it is culturally sensitive and adaptable to the language and linguistic needs of diverse groups of people.
Q: If a younger family member has been diagnosed with cancer, could older generations be at greater risk? Or only future ones?
Dana Zakalik says: Yes, older generations may be at increased risk. It is possible that individuals in the prior generations may have a familial/genetic predisposition to cancer, but have not yet manifested it. They are still potentially high risk, and just because they have not yet developed a cancer does not mean they couldn't do so in the future.
Q: If several of my family members have been diagnosed with different types of cancer (breast, colon, and lung), could my family be at risk for cancer in general or are we all at risk for each type specifically?
Dana Zakalik says: A family history of different types of cancer can be a hallmark of a specific hereditary cancer risk syndrome (e.g. Li Fraumeni syndrome, Cowden's Disease, Hereditary Breast and Ovarian Cancer, Lynch syndrome); however it may also indicate a general risk (perhaps related to environmental and lifestyle factors-tobacco, toxins, diet, or perhaps related to as yet undiscovered genes, or a combination of both).