|Dr. Joseph Cubells|
Dr. Joseph Cubells is an Emory psychiatrist who focuses on working with adults with developmental and behavioral disorders, especially Autism Spectrum Disorders (ASD). He is on the cutting edge of using molecular genetics to identify genetic anomalies in his patients with the aim of improving and refining treatment packages. I spoke with Dr. Cubells about his work and the ethical implications of the use of genetic microarray tests with patients. After providing more details about how he uses molecular genetics in his practice, I will focus on our discussion of two primary issues related to his work: (1) the communication of genetic testing procedures and results to families and, (2) the role of health care systems in the widespread use of these tests.
Dr. Cubells is primarily engaged in clinic work. He has over 200 cases and works exclusively with adults (he does not see patients under the age of 16). Molecular genetics is one technique used in his patient management strategies: “I am very interested in the role of molecular genetic testing in the care of people with neurodevelopmental disabilities. Not so much establishing a diagnosis of autism though because autism is a behavioral diagnosis.” In other words, because there is no genetic or otherwise biologically based test currently available for autism, Dr. Cubells and his team are interested in diagnosing other genetic differences, such as Phelan McDermid Syndrome which occurs when a chromosome is deleted after conception (de novo) and can lead to a variety of physical and developmental disabilities. This condition, and many other genetic anomalies, may contribute or directly lead to the development of autistic characteristics. Most professionals, including myself and Dr. Cubells, now agree that there is not a single ‘autism’ but, rather, many different ‘autisms’ with many different causal pathways, both genetic and environmental.
Last November, Dr. Cubells and his team presented a paper on their use of molecular genetics in direct patient care at the American Society for Human Genetics. They sent chromosomal microarray tests1 to be analyzed for 44 of their patients. Seven of these tests “came back with definitely clinically relevant differences that had not been previously diagnosed.” This is a rate of 16%, which, for Dr. Cubells, is “a substantial and important rate.” This rate may seem small but the impact of these findings are critical. For example, among those seven, one adult male’s test showed a deletion of the monoamine oxidase (MAO) A and B gene. This effects of this deletion are similar to the effects of taking a MAO inhibitor (MAOI), a type of pharmacological treatment for depression. Both this medication and this genetic deletion can lead to a fatal hypertensive crises if a person consumes tyramine (found in many aged or fermented foods, foods high in protein, and some alcoholic beverages) or in the presence of sympathomimetic drugs, which mimic transmitters such as catecholamines (i.e., epinephrine, norepinephrine, and dopamine). Because this genetic deletion was identified, the patient now wears a medic alert bracelet stating that he must be treated as a patient on a MAOI to avoid unexpected drug reactions. This knowledge is potentially life-saving.
These microarray genetic analyses can help refine patient management; however, the actual purpose and results of tests are difficult to accurately communicate to families. Dr. Cubells related another story of an adult who has significant autistic characteristics for whom his team identified another type of anomaly: a 15q13.3 deletion for which a small part chromosome 15 is deleted in each cell. They discovered that this participant’s mother has the same deletion, however, unlike her son, does not show any of the developmental delays. The man’s grandmother, however, also has the deletion and exhibits some developmental delays. This patient’s cousin is recently married and is wondering if he should be tested for this deletion. I asked Dr. Cubells what, in cases like this, a genetic counselor or clinician is ethically responsible to communicate to families regarding the implications of obtaining the tests and the implications of the results. This issue is an important concern for eventual pre-natal diagnoses of autism as well as for the project I am working on as the current Neuroethics Program Scholar, which involves considering the implications of using eye-tracking technologies for early, presymptomatic screening of ASD.
|The gene copy number (also "copy number variants" or CNVs) is the number of copies of a particular gene in the genotype of an individual.|
Dr. Cubells responded that “the first thing you have to make clear is there is a lot of uncertainty.” For cases like the one described above, he would start by explaining that the test will only tell him whether he carries the deletion. If he does not, then there is an “infinitesimally small” likelihood that his future children would have that deletion. However, if he does carry the deletion, things are a much more complicated. There is a big chance that this gentleman’s children would have learning or developmental difficulties, however, as the patient’s mom exemplified, there could also be no discernible influence. “And so the range of possibilities ranges from very challenging to fine.” Regardless, at this stage, Dr. Cubells believe that with this particular chromosomal variation, or copy-number variant (CNV), there are “reasonable odds” that there will be challenges but the field is not ready to be quantitative about it. This is the kind of information, he says, of which genetic counselors must be aware.
There are significant differences in the understanding of risk between the lay public and professionals.2 Explaining probabilities to patients or families is difficult, but Dr. Cubells urges that the physician’s role is “to be helpful when he can and to give them [the family and patient] as much information as he can to explain things.” This information should include an explanation of the meaning and difference of variable penetrance and variable expressivity. The former is the proportion of people who carry a particular gene that also expresses and particular trait, or phenotype. The latter describes the differences within this expression, or the ranges of phenotypes linked to a particular gene or genetic anomaly. This information is often confusing for patients and families to understand. It is critical that patients understand these terms in order to consent to taking part in a microarray test and for comprehending the consequences of test results. Given that the responsibility of making decisions lies with the patient and family, this information needs to be communicated clearly and reliably.
We also discussed issues related to the cost of these genetic arrays and resource allocation. Dr. Cubells explained that genomic micro-arrays cost, at a minimum, around $800. If the company wants to stay in business and possibly make a profit, then they need to charge around $1400. He admits that this amount of money can be also used towards valuable and efficacious behavioral or psychological treatment. And so where should we put our resources? He admits that, despite the obvious benefits of the work he is doing, he is “ambivalent about pushing the importance of genetics in autism because [he] spends a lot of time explaining what ought to happen but the resources aren’t there.” This is a large debate in the field. Many self-advocates and family members struggle, knowing that there is a lack of funding for research on quality of life issues and services, especially for adults who lose a host of services, such as instruction on daily living skills as well as occupational and speech therapies, once they age out of the public school system at the age of 21.3
“But on the other hand,” Dr. Cubells explains, “we do need to understand things at the level of etiology. We need to know if a person has Phelan McDermott versus 15q versus 22q114 because even now there are clinical implications for that.” Dr. Cubells sees a problem in the lack of reimbursement for genetic counselors who see patients with psychiatric problems; insurance companies do not have to pay for this kind of consultation. He says this situation needs to change, but the only way this change will happen is for politicians and professionals to work towards changing the minds of insurance and health care administrators.
Cost is a real barrier to access to emerging medical technologies like this for many families. This means that critical information will potentially not be available to many patients unless these tests become a mandated part of health care coverage. It is also possible that tests like these will become part of standard pre-natal check-ups, in which case a host of other ethical concerns arise. Disability activists, especially those adherent to neurodiversity, see pre-natal diagnostics of disabilities as an attempt to eradicate disability and difference from the human population—a eugenic enterprise. Additionally, as was discussed in my last post, cultural and faith-based backgrounds of families may mean less acceptance of the use of these technologies. Families may rely on more spiritually-based explanations of disabilities and so may not be open to discussions of genetic causes, which can be seen as more chronic and stigmatizing. Finally, for many of the genetic anomalies identifiable by these tests, no reliable treatments are available. There are educational and behavioral therapies for autism and related disorders; however, there is no guarantee that any intervention will dramatically change behavior or if, given the variability of autistic manifestation, any intervention will even be necessary! These issues will be discussed more fully in my next blog post, where I describe the impact of the use of eye tracking technologies to identify autistic markers in infancy.
This discussion reminded me of a recent op-ed in the New York Times in which the columnist, Nicholas Kristof, called for more attention in the media and government on mental health. We may be working in the right direction as the Affordable Care Act does include mental health care, but costs remain high and the consequences of these costs are having real effects on real lives. Bringing the impact of psychiatric, intellectual, and developmental disorders has on the quality of life of diagnosed individuals and their families into the public realm is imperative to obtaining more funding for services and more research on how to develop, implement, and distribute these services most effectively. As genetic testing and prescreening for psychiatric conditions continues to become more advanced, I agree with Mr. Kristof and Dr. Cubells. Improving coverage for psychiatric services should be a high priority issue for politicians, health care administrators, scientists, physicians, and, most importantly, families.
Dr. Joseph Cubells is a psychiatrist whose clinical and research interests lay in molecular genetic factors of developmental and behavior disorders, such as autism, schizophrenia, and major depression. He is the Medical Director and Attending Psychiatrist at the Emory Autism Center where he work with adults on the autism spectrum and with genetic and chromosomal disorders that lead to various psychiatric disorders.
- A chromosomal microarray test is a new method of detecting alterations in a person’s DNA. Specifically, these tests look for areas on the DNA with too many or too few copies of genetic material. This method is more specific than earlier genetic tests, thereby allow for more exact maps of the DNA and, ostensibly, the ability to identify more anomalies. For more information, see The American College of Obstetricians and Gynecologists’ Committee Opinion on the use of this test in prenatal diagnosis here: http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Genetics/The_Use_of_Chromosomal_Microarray_Analysis_in_Prenatal_Diagnosis.
- For example, see: Hamepl, J. (2006). Different concepts of risk - A challenge for risk communication. International Journal of Medical Microbiology, 296(S1): 5-10; Miller, A.M, Hayeems, R.Z, & Bytautas, J.P. (2010). What is a meaningful result? Disclosing the results of genomic research in autism to research participants. European Journal of Human Genetics, 18: 867-871; McMahon, W.M., Baty, B.J., & Botkin, J. (2006). Genetic counseling and ethical issues for autism. American Journal of Medical Genetics Part C (Semin. Med. Genet.), 142C: 52-57; Slovic, R. (1987). Perception of Risk. Scienze, 236(4799): 280-285.
- For more explanation of this perspective, see this report by the Autistic Self Advocacy Network (ASAN), “ASAN expresses concern regarding new HHS report on autism research” at http://autisticadvocacy.org/2012/07/asan-expresses-concern-regarding-new-hhs-report-on-autism-research/.
- These are all genetic disorders associated with autistic phenotypes. Phelan-McDermid is “the result of a disruption of the SHANK3/ProSAP2 gene on the terminal end of chromosomee 22,” according to the website for the Phelan-McDermid Syndrome Foundation (www.22q13.org). 15q and 22q11 refers to partial deletions of chromosomes 12 and 22 that leads to a variety of developmental disorders.
Want to cite this post?
Sarrett, J. (2014). Ethics, Genetics, and Autism: A Conversation with Dr. Joseph Cubells. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/04/ethics-genetics-and-autism-conversation.html