The Potomac School
Teacher: Dr. Isabelle Cohen
Huntington’s Disease (HD) is a fatal, autosomal dominant, neurodegenerative disease with no cure. HD is characterized by progressive motor-skill degradation, cognitive impairment, and psychiatric disorders1. The disease is caused by a mutation of the huntingtin (HTT) gene which codes for the huntingtin (HTT) protein1. The mutation is defined by an expansion of a CAG repeat chain in the exon-1 region of the gene1. The symptoms of HD arise due to the toxic effect of the mutated HTT protein on neurons in the basal ganglia, which are brain cells participating in the control of motor functions, cognition and emotion1. Having the faulty gene guarantees the development of HD symptoms on average between the ages of 30 and 502. The children of an afflicted person have a 50% chance of inheriting the mutation from that person1.
A dilemma for a newly-diagnosed individual with children, is whether to inform them of the possibility that they may have inherited the faulty gene. This is the situation facing Jonathan who has decided not to tell his daughter Sarah about his HD.
The difficulty in assessing Jonathan’s decision arises from the conflict between Jonathan’s rights and Sarah’s rights. Jonathan is entitled to keep information about himself secret and may choose to withhold the truth out of a desire to protect Sarah. A parent’s natural duty is to ensure their child’s well-being. Thus, Jonathan may think it his duty to shield Sarah from knowing that she is at risk and from the corresponding emotions of anxiety for the future, feeling overwhelmed by caregiving duties and uncertainty about family planning decisions3,4. Jonathan may wish to attempt to let Sarah live a life unaffected by the reality of HD. He may be worried that Sarah would limit herself from possible opportunities to start a family, or pursue a career in fear that HD would compromise her future.
On the other hand, Sarah has the right to know her own genetic information, because regardless of Jonathan’s wishes, this information will affect her life. In this sense, Jonathan’s parental duty to Sarah dictates that he should empower her by giving her the opportunity to make informed decisions about her future life and family.
Such are the arguments that the genetic counselor Karen may discuss with Jonathan as she attempts to guide his thinking, but ultimately disclosure can and should only happen with Jonathan’s consent. This would be consistent with guidance from both the American Medical Association and The American Society of Human Genetics5.
Telling Sarah about Jonathan’s diagnosis, empowers her by giving her choices. She would be in a position to exercise control over some outcomes of her life, instead of blindly following her fate. One of the most significant issues to people at risk of HD, is the question of having children. Knowing her status, Sarah can choose to utilize preimplantation genetic diagnosis with IVF to ensure that her future children are free from the HD mutation6. Taking advantage of such a technique would effectively end HD in future generations of Jonathan’s family. Also, awareness of being at-risk may give Sarah the incentive to make appropriate financial and healthcare decisions. Finally, Sarah has the option to undergo predictive genetic testing to discover if she carries the mutated HTT gene. This choice is intensely personal and is entirely dependant on her individual psychology.
In addition, there is active ongoing research on ways to slow down or even prevent the onset of HD symptoms. Zinc finger proteins and RNA interference are two methods which aim to reduce the production of the mutated HTT protein at the transcriptional and the translational level, respectively7. Another proposed technique attempts to use the gene editing tool CRISPR to deactivate the mutated HTT gene8. These approaches are still in early experimental stages and are not available to afflicted individuals. However, given Sarah’s relatively young age and the possibility that she may not exhibit symptoms for many years, there is a chance, albeit small, that some technique may become available to her in time. Being aware that she is at risk may ensure that she is informed and could take advantage of such advances in the field of HD.
Jonathan faces a complex personal decision with high stakes. The difficulty of coming to terms with the reality of a devastating disease like HD can be overwhelming. But, ultimately the ability to empower his daughter to make the most of the hand she is dealt should be the definitive factor in deciding to inform Sarah of the truth.
Venkateswara, Rao P., et al. “Huntington’s Disease - A Review”, Theranostics of Brain Disorders, 2.2 (2017): 555581-555586.
Roos, Raymond A., “Huntington’s Disease: A Clinical Review”, Orphanet Journal of Rare Diseases, 5 (2010): 40-47.
Williams, Janet K., et al. “The Emotional Experiences of Family Carers in Huntington’s Disease”, Journal of Advanced Nursing, 65.4 (2009): 789-798.
Quaid, Kimberly, A., et al. “What Were You Thinking?: Individuals At Risk for Huntington’s Disease Talk About Having Children”, Journal of Genetic Counseling, 19.6 (2010): 606-617.
Laberge, Anne-Marie and Wylie Burke, “Duty to Warn At-Risk Family Members of Genetic Disease”, American Medical Association Journal of Ethics, 11.9 (2009): 656-660.
Blancato, Jan, K., et al. “Preimplantation Genetics and Other Reproductive Options in Huntington’s Disease”, Handbook of Clinical Neurology, 144 (2017): 107-111.
Huang, Wen-Juan, et al. “Huntington’s Disease: Molecular Basis of Pathology and Status of Current Therapeutic Approaches (Review)”, Experimental and Therapeutic Medicine, 12 (2016): 1951-1956.
Monteys, A.M., et al. “CRISPR/Cas9 Editing of the Mutant Huntingtin Allele In Vitro and In Vivo”, Molecular Therapy, 25.1 (2017): 12-23.