Epilepsy Essentials: Caregiver Response to Genetic Diagnosis of Developmental and Epileptic Encephalopathy

Caregivers of children with developmental and epileptic encephalopathies (DEEs) often face uncertainty regarding their child’s medical condition. DEEs are defined as a group of rare neurologic conditions that occur during early childhood. Children with DEEs often experience severe epilepsy and require aggressive treatments.^1-3 Technologic advances in next-generation sequencing (NGS), commonly used for gene panel testing and whole exome sequencing (WES), have significantly improved the diagnostic yield to ~30% for those with DEEs.³ At the same time, NGS can find variants of unknown significance (VUS), for which the impact of an identified genetic variation is uncertain; these results can complicate the clinical picture without offering a clear answer. In this scenario, further interpretation of whether a VUS may be causative of an individual child’s phenotype may not be possible given insufficient knowledge of a gene or disease to date, limiting the understanding of an illness. In this manner, NGS can provide information with uncertain interpretation that can add to the diagnostic odyssey for both caregivers and those with a DEE with an unknown cause.

Other burdens for caregivers of children with DEEs include coping with their child’s condition and accessing medical insurance coverage, which increase the emotional burden of an unknown genetic diagnosis.⁴ Caregivers have reported depression, anxiety, and stress in response to caring for a child with early-onset epilepsy.⁵ The quest for an accurate diagnosis can increase this burden, considering that obtaining coverage or funding for WES can be challenging because it is not covered by all insurance companies⁶ and caregivers of children with epilepsy already spend on average $7522 annually on direct medical costs.⁷

Emerging studies are beginning to address the complex experiences of caregivers for people with DEEs and many emphasize the importance of qualitative and quantitative methodologies.^5,8,9 Considering the uncertainty and challenges associated with caring for a child with DEEs, a broader analysis of caregiver experiences is needed to inform pediatricians, neurologists, and genetic counselors on how to provide further support for affected families. In this article, we discuss our use of medical anthropologic methodologies to analyze caregiver illness accounts; based on this analysis, we make concrete suggestions for how health care professionals can enhance their support for caregivers of children with DEEs.

Interviewees

We recruited 9 caregivers of children with early-onset epilepsy and 3 genetic counselors at a large urban hospital in the Midwest region of the United States. Caregivers were recruited by physicians in the pediatric neurology division of the hospital and signed an institutional review board–approved informed consent before being interviewed. The diagnoses and ages of the children cared for by these individuals are provided in Table 1.

Interviews

Because of the COVID-19 pandemic, semi-structured interviews had to be done via telephone. These interviews were 30 to 90 minutes long and followed an interview guide with open-ended questions (Table 2). The purpose of the interview was to gain more insight into caregiver experiences around the time of diagnosis and genetic counselor interactions with families during the same period. Interviews were conducted between September 2020 and April 2021.

Analysis

Telephone interviews were transcribed and analyzed utilizing a thematic analysis¹⁰ by the first author, following the 6-step guide by Braun and Clarke¹¹ and accounting for anthropologic concepts when creating codes and finding recurring themes. Alternative medicine, uncertainty, and caregiver–doctor interactions were considered when conducting the thematic analysis.

Caregiver Uncertainty and Illness Experiences

Many caregivers’ journey was heavily influenced by the experience of a diagnostic odyssey or the stress of anticipating and waiting for a final diagnosis. Whereas a biochemical result suggested a specific genetic diagnosis early on for some, having to undergo multiple rounds and testing modalities to arrive at a genetic diagnosis intensified the emotional burden for others. Many were also first-time caregivers; speaking with physicians was an important part of coping with their child’s condition. Caregivers valued physicians stating that they might not have an immediate answer to the child’s rare condition but were working to find an answer, especially as some caregivers experienced challenges related to communication and social–emotional connection (ie, bedside manner) with previous physicians. In one case, when the caregiver of child B showed a previous pediatrician a video demonstrating the infant making strange movements, the practitioner said the child had an exaggerated startle reflex, but presentation to an emergency department resulting in hospital admission prompted prolonged EEG monitoring and identification of hundreds of seizures per hour in the 2-month-old child.

Although some caregivers experienced uncertainty, isolation, and grief after receiving a genetic test result, others felt that having a diagnosis was a step forward in finding solace, peace, and hope. Those who did not find their child’s test result comforting noted the limitation that it could not fully inform how their individual child’s condition may manifest in the future. The caregiver of child A found the diagnosis confusing—“a bunch of letters and numbers”—and expressed experiencing a grieving process in trying to process the child’s condition. In contrast, the caregiver of child B found comfort in the identification of a VUS with disease association that matched the child’s phenotype, allowing the caregiver to build a community with other caregivers of children with that diagnosis.

There was a spectrum across caregivers regarding how much they relied upon genetic counselors. Some valued having another individual explain genetic testing results slowly and methodically, which provided more comfort during the illness journey, whereas others felt their questions were already answered. Certain caregivers also wished they received more resources regarding support systems and literature on rare genetic disorders or genetics from their genetic counselor.

Culture and Religion in Medicine

Culture and religion play an important role in many individuals’ lives and shaped how some caregivers coped in response to receiving genetic testing results. Some families turned to alternative medicine or religion to provide additional healing. According to the caregiver of child I, the child received different combinations of medications before the correct treatment was found. This caregiver also decided to utilize some Ayurvedic medications to calm the child, implementing a weekly treatment of maha kalyanaka ghrita, a type of ghee (clarified butter).

The caregiver of child A relied on religion and visited the pundit to cope with the news of the child’s rare genetic condition:

“I started digging deep to find my faith. I was desperate to be able to help [my child]. So, in the middle of the pandemic, I met a pundit at a temple to pray over [my child]. This balance [religion and science] has helped me through this.”

Language or cultural barriers may exist when caregivers are communicating with physicians or other health care professionals. According to genetic counselors, genetic counseling programs are discovering ways to navigate culturally sensitive topics, such as trying to normalize asking questions about ethnicity and family history by stating “this is a question we ask all families.” Some language barriers have been mitigated by forgoing some technical details that may lead to confusion and instead effectively communicating genetic testing results while asking caregivers what they intuit from different terms.

Medical Insurance Barriers to Testing and Treatment

Although many caregivers received their child’s diagnosis through genetic testing, some experienced challenges in receiving a test or treatment because of lack of coverage from their insurance carriers. Genetic counselors work with families and insurance companies to preauthorize or certify payment and reduce costs to a family wherever possible. According to genetic counselors, WES coverage is specific to a patient’s insurance plan, and if an insurance payer is considering preapproval for WES but does not consider testing for the condition medically necessary, testing coverage may be denied. Some caregivers, including the caregiver of child F, did not experience difficulties in receiving insurance coverage for WES because their child had sufficient clinical symptoms to clearly warrant coverage, but this was not the case for all. Genetic testing was inaccessible to the caregiver of child B because coverage for gene panel testing after receiving a VUS result was denied by their insurance company. The caregiver of child H was concerned about receiving adequate insurance coverage after the child aged out of an early intervention program. Because child H’s condition is extremely rare and incompletely understood or recognized by insurance companies, the caregivers of child H must use the less specific and phenotypically diverse diagnosis of cerebral palsy.

What Can Health Care Professionals Do?

Uncertainty was central to many of the experiences of caregivers, who did not know how to navigate a new illness journey, especially when genetic test results, including VUS findings, often did not provide the answers caregivers sought. As a result, communication and compassionate care from physicians and genetic counselors before and after receiving the genetic diagnosis were very important in caregiver illness journeys. Clinicians can continue to promote dialogue among caregivers considering that clinician communication is key to improving the understanding of genetic test results. Physicians can continue showing empathy during an emotional and uncertain time and a willingness to explore all possible treatment options. More support can be provided to caregivers, which can include providing relief through humor, light-hearted conversations, and effective distractions.^9,12 Physicians can provide useful resources by connecting caregivers with other health care professionals, updated literature, or online platforms to learn more about their child’s condition and build a community with others caring for children with the same diagnosis.⁴

It is important for physicians and genetic counselors to communicate effectively with patients from diverse backgrounds and be aware of alternative healing paradigms. Some caregivers incorporated religion and alternative medicine to help ameliorate their child’s condition. Allowing for and gaining awareness of different cultures and diverse forms of healing can be important for health care workers when conversing with caregivers about their experiences and coping mechanisms. The use of translators and resources to improve understanding of genetic test results may be helpful in reducing language and cultural barriers.

Many caregivers’ children experience genetic testing inaccessibility due to a lack of insurance coverage. Although health care barriers persist, genetic counselors can continue to advocate for families by providing medical justification to increase the likelihood that necessary testing and treatment will be available and affordable. Furthermore, physicians can help advocate for patients and identify alternatives when insurance companies are not in agreement with the necessity of genetic testing.

Limitations

This study has a small sample size and was conducted remotely over a span of 7 months. Bias exists as participants were recruited from a single hospital. More studies are needed to investigate caregiver coping mechanisms and the care needed to improve caregiver emotional burden and quality of life.

Conclusion and Future Directions

The purpose of this investigation was to use medical anthropologic methodologies to explore the lived experiences of caregivers of children with DEEs and account for alternative forms of healing. There is much to learn regarding rare genetic causes of conditions like DEEs and precision medicine will play an important role in translating that diagnosis into a treatment. Uncertainty and challenges may continue to be a part of many caregiver experiences and more studies should be done to promote awareness and suggestions to improve the lives of affected families. Furthermore, health care workers at different levels of responsibility and patient and family interaction can continue to learn from diverse caregiver stories to improve the patient’s quality of life and promote cultural competency. More resources and support systems can be implemented to support caregivers, decrease caregiver burdens, and increase health care access.

Acknowledgment

Thanks to Dr. Gertler and the Princeton University Department of Anthropology for their support of this senior thesis project.