The question came during my visit with the parents of a little girl who had passed away two weeks before. We reviewed the results of the whole-exome sequencing, which is an analysis of the 1 to 2 percent of the genome involved in protein-coding, in search of answers for their daughter, Leah. We all knew the results had come too late, but there were lingering questions that her parents needed answers to.
Most of my genetic counseling work has been proactive, searching for information about personal and family health risk, with the aim of providing information for medical or reproductive management. However, in this case, one of the first questions I was asked was: “Did we make the right decision?”
This question made me realize just how powerful genetic information is, beyond the usual hype of personal, individualized medicine and beyond my current work as a cardiovascular genetic counselor. The psychosocial “heaviness” of the implications of genetic information continually surprises me. “Did we make the right decision?” This was a question asked by a family looking for much more than a simple diagnosis.
It was a question my clinical genetic counseling training had never exposed me to. This was life at its realest; this was working with families who were experiencing the scariest times of their lives, families who were navigating complexities I had never known in my own life. This question made me contemplate the meaning of genetic testing, the existential implications that results can have beyond simply uncovering unknown diagnoses and providing information about familial recurrence or health risks. Genetic information has the potential to affect life in many more ways than most routine medical tests do, and I do not want the healthcare and research worlds to forget this.
Over the first several months of Leah’s life, her condition had quickly deteriorated. Her microcephaly and epileptic encephalopathy had been too formidable. They were intractable to all available treatments.
The suffering permeating each of her epileptic episodes was palpable to her family. They were desperate for possible explanations and hopeful for any possibility of treatment. All of the swirling notes of fear, uncertainty, vulnerability, anxiety, and frustration became the backdrop of conversations with the family. The diagnosis was unclear, and as a result, the prognosis was too.
“Genetic information has the potential to impact life in many more ways than most routine medical tests do, and I do not want the healthcare and research worlds to forget this.”
I am always amazed how parents find ways to traverse the probabilistic mazes of hope and uncertainty for their children, especially ones with unknown or rare diagnoses. This was the true “diagnostic odyssey” experienced by families I have worked with. Leah’s initial battery of genetic testing and screening included chromosome microarray, extensive blood and urine metabolic screening, a 20-gene epilepsy panel, and repeated brain imaging and electroencephalograms. They all were normal. Our team quickly turned to whole-exome sequencing, and I had to explain that the family would have to wait up to three months for results. I pushed the lab to have it done sooner, given the gravity of Leah’s situation.
Leah’s nadir came after a severe epileptic event and a concurrent hospital admission. Her development had slowed and then worsened. After the first few months of her life, the seizures and tremors turned relentless. And then the decision that no parent ever wants to consider had to be made: support was withdrawn, and Leah passed away with her family beside her.
The genetic testing results came back about two weeks after Leah’s passing. We met with her parents to review her whole-exome sequencing. In these cases, parents who lose a child need someone to talk to and someone to listen as well. It is striking how much better our healthcare system could be at facilitating bereavement for families in these situations. It is important to provide psycho-social support to patients and families during and after events like this.
Whole-exome sequencing identified a mutation in the SPTAN1 gene, confirming Leah’s diagnosis of a rare type of infantile epileptic encephalopathy, an umbrella clinical diagnosis comprising several different disorders associated with mutations in multiple genes. This SPTAN1 mutation occurred de novo, meaning it was not inherited from a parent. This small piece of information was crucial for the family to hear, because they were concerned about recurrence in future children. This finding provided some peace of mind that the recurrence risk was probably low.
As we reviewed information about the SPTAN1 gene and how it malfunctions to cause microcephaly, severe intellectual disability, and hypsarrhythmia, I could see tears welling up in their eyes. At the end of my brief discussion, I asked them what questions they had. Leah’s father, behind teary eyes and a trembling voice asked, “I just want to know that our decision was right. Was there any chance if we hadn’t withdrawn support? Did we make the right decision?”
“To share in this vulnerable moment solidified why compassionate, comprehensive genetic counseling should accompany most genetic testing.”
Genetic counseling training has historically and justifiably emphasized nondirectiveness in discussions with families, though dogmatic use of nondirective counseling has received reasonable criticism in certain situations. As a genetic counselor, part of my work involves identifying the psychosocial needs families have in the face of genetic testing results and advocating for the families. His question caught me by surprise, though. This was the first time genetic testing took on a new meaning for me — after the death of a patient. It was beyond identifying the cause of her epileptic encephalopathy. The motives for this type of question could be dissected endlessly, and ultimately, no one may truly know but the family. However, I think the family was hoping for closure and justification: “What on earth happened to our daughter, and why? Would she have improved? Was there hope? Would she have continued to suffer?”
Of course, the family was needing a name, a diagnosis, and an understanding of why their daughter could not get better. Their additional concern about recurrence in their other children was warranted. However, there was a sense in this moment that they had lingering questions about their decision. Perhaps it was fear of regret or judgment from others. My reflection on their question afterward highlighted, among other things, the search for meaning that may come with genetic testing, especially in grave situations and in the context of the loss of a child. The question “Did we make the right decision?” came at the culmination of the passing of a beautiful little girl whose family had traversed a months-long diagnostic odyssey. To share in this vulnerable moment solidified why compassionate, comprehensive genetic counseling should accompany most genetic testing.
As a genetic counselor, cases like these can be frequent, and my reflections on them will hopefully help my work grow and improve. There is a weight behind most genetic testing, beyond simple diagnostic and prognostic information. This is information that people are crafting their worldviews around, and actions based on it may influence so many factors in a person’s life: medical management, psychosocial well-being, family dynamics, reproductive decisions, and even deeper questions about meaning and loss.
“Did we make the right decision?” I don’t think they could have made a wrong decision, and I wanted them to know this. They had someone on their side, no matter what.