Background
Undiagnosed diseases are common, affecting approximately 30 million Americans, and are associated with high rates of morbidity and mortality [
1‐
3]. They include rare disorders which are difficult to recognize, atypical manifestations of more common disorders, yet to be described conditions and manifestations that cannot be explained medically. The majority (~80%) of undiagnosed diseases are believed to have a genetic etiology [
4]. Undiagnosed disorders are often not amenable to the traditional diagnostic approaches and the lack of a diagnosis leads to repeated clinical consultations and laboratory testing, causing substantial personal and familial emotional and financial stress [
1,
2,
5‐
11].
Both children and adults are affected with undiagnosed diseases, though possibly with different experiences. Parents of pediatric patients continue to struggle and make their way through the “diagnostic odyssey” of repeated clinical consultations and testing, with the purpose of finding information about their child’s long term health and recurrence risk information for the family [
12]. In contrast, adults who have medically unexplained symptoms often feel that they need to continually legitimize their illness to medical providers and may find themselves in a situation where further diagnostic evaluation may not be offered to them [
13,
14]. Thus, regardless of age, undiagnosed patients have extensive medical and psychological needs related to obtaining a diagnosis and appropriate management. Healthcare providers caring for undiagnosed patients also face challenges; needing extra time to parse out the symptoms and signs, determine if further diagnostic tests/procedures are necessary, initiate or participate in interdisciplinary provider communication and following up on results, all of which can be difficult to accomplish, even within a tertiary healthcare system. These multiple and unique challenges are elements that the Undiagnosed Diseases Network (UDN), funded by the National Institutes of Health, is designed to help manage. The UDN is a nationwide network-based research study established in 2014 whose purpose is to bring together clinical and research experts from across the United States to solve the most challenging medical mysteries using advanced technologies such as genome sequencing (
https://undiagnosed.hms.harvard.edu). Currently, seven academic medical centers have been named as UDN clinical sites and receive applications for evaluation of undiagnosed adult and pediatric patients from all over the country. The review of each application prior to acceptance includes a comprehensive examination of the medical records for the medical history, family history and prior laboratory tests and procedures. Many UDN applicants whose medical records are under review contact the clinical sites to provide incremental bits of information through multiple emails and phone calls that they believe will facilitate their acceptance into the network. At the Duke University UDN clinical site a process was initiated to systematically request written narratives from all UDN applicants, to gather the patient/parent’s perspective of the illness and prior experiences all at one time.
Patient narratives, oral and written, are increasingly being recognized as important tools in modern medicine, providing the patient an opportunity to place their illness experience within the context of their life; additionally the narratives in and of themselves may have therapeutic value [
15,
16]. For medical providers the narratives provide the opportunity to grasp and honor the meaning of the patient stories and act accordingly on their patient’s behalf in an engaged manner [
17,
18]. Ground-breaking analyses of patients’ illness narratives by Frank [
19] resulted in the identification of three types of narratives that offer insights into how patients experience illness and provide constructive methods for quality improvement in healthcare. The definitions of these narrative types have since been expanded, based on their application to different chronic illnesses, such as chronic fatigue syndrome, childhood cancer and medically unexplained symptoms [
13,
20‐
22].
The restitution narrative is the least frequent among chronically ill individuals. This narrative reflects a transient nature of the illness with the patient expecting to recover from it. The narrative type usually occurs in the early stages of a chronic illness, before its longstanding nature becomes evident [
21]. Restitution can also include the acceptance of a “new normal”, which may include acceptance of a negative outcome or an unresolved chronic health concern [
22].
The chaos narrative is characterized by the concepts that life will never get better and no one is in control. This narrative reflects suffering, loss, inability to make plans, uncertainty, fear, rejection by clinicians and by others, is disjointed and disorganized, and can be difficult to hear and/or read [
19]. In the literature it is exemplified by the narratives of adults with unexplained medical symptoms and chronic fatigue syndrome [
21].
The quest narrative is one in which the patient sees the illness/disorder as a challenge and an impetus for change and believes that something can be gained through the experience. Additionally, parental quest narratives emphasize the positive attributes of their child and their gaining new parental and advocacy skills as a result of the child’s illness [
22].
While these typologies provide a framework for the classification of illness narratives, they are often fluid with elements of more than one type found in the same story [
19,
22]. The narratives may also transition from one type to another as the illness progresses or improves. Whitehead et al. in their analyses of interviews with 17 individuals diagnosed with chronic fatigue syndrome found that the narratives often started with restitution (individuals experienced symptoms with an assumption that with treatment, they would be healthy again) and then the narrative moved into chaos when symptoms got worse or did not resolve. Subsequently, the majority of the chaos narratives transitioned to the quest type, with the patients developing a positive outlook on their situation. Similarly, Bally et al. in their analyses of 16 parental narratives related to childhood cancer, found that these stories contained elements of all three types of narratives. The quest narratives of the parents included the positive effects of the child’s illness on their parenting and their gaining deeper appreciation for the child and family. Nettleton [
13] [
14] in their study of 18 adults with medically unexplained symptoms reported that living with an undiagnosed condition resulted in chaos due to ‘living with uncertainty;’ ‘issues of legitimacy;’ and a ‘resistance to psychological explanations of pain and suffering.’ Thus, illness narratives differ based on the type of illness (diagnosed or undiagnosed) and whether the narrative is being told by the affected individual or by a parent on behalf of their child.
Despite the increasing importance of illness narratives, no study has analyzed illness narratives of both adults and children who have an undiagnosed disorder/illness. To address this void, we conducted a retrospective study of written narratives of undiagnosed patients who applied to the UDN. Our objectives were: 1) To analyze the content of the narratives in the setting of whether the writer was an adult proband writing for himself/herself or a parent on behalf of their child, and 2) To analyze the structure of these narratives in the context of Frank’s narrative typologies [
19]. Obtaining insights into the illness experiences of the UDN applicants would facilitate an individualized approach to these patients as well as inform the patient/provider communities of rare and undiagnosed diseases about the illness experiences of these individuals.
Discussion
This study analyzed for the first time, the illness narratives pertinent to both adults and children with undiagnosed diseases. Overall, the burden of living with an undiagnosed condition is high, with suffering, frustration and uncertainty. We found both commonalities and important differences in the content of the narratives and in the typologies between the adult proband and parental narratives.
Narrative content
Not surprisingly, both the probands and the parents applied to the UDN after having exhausted all other options. While both groups had high expectations of the UDN, the probands wished to resume their former lives, while the parents recognized that their child was unlikely to completely recover and wanted information how to better medically manage their child. This may be a reflection of the early onset and severe manifestations seen in children with difficult to diagnose disorders; for the probands who often developed symptoms abruptly, a clear awareness of the demarcation between being well and falling sick persisted, such that they yearned to become well again.
The medical information in both groups reflected important reasons for why they applied to the UDN- for many the symptoms were getting worse and for all there was no answer. A striking difference between the proband and parental narratives was the lack of objective findings in most of the proband narratives, in contrast to the detailed objective findings in the parental accounts, again reflective of the multiple and serious features of pediatric undiagnosed diseases. The narratives were especially informative in providing information that was not in the medical records, such as the proband/parent’s impression of potential causes/diagnoses or a more accurate timeline of when certain events or symptoms presented. This information could be used by the UDN team to either obtain additional records that could be relevant or to address these problems specifically during the review and evaluation process.
The narratives provided insight into the lived illness experiences of the proband or the experience as described by the parent. Narrators appreciated being given an opportunity to tell their story in their own words, perhaps attesting to the power of narrative medicine [
17]. Parental narratives are widely accepted as giving voice to the child’s experience, which may go unsaid otherwise and so are as valuable as the proband narratives [
16]. A commonality in both the proband and parent narratives was the feeling of not being heard by their medical team and/or being categorized as a difficult patient or parent. While the term “difficult patient” has a negative connotation, a patient may be perceived as difficult because the health care provider cannot identify the problem, is unable to diagnose the disorder, and/or is unable to help the patient to improve their health outcome [
27]. These are characteristics of the undiagnosed patient which may contribute to their perception of not being heard. Health care providers and in particular, genetic counselors, are positioned to help facilitate medical care for these patients and should consider the emotional component associated with being undiagnosed, thus meeting their needs with understanding and empathy.
Narrative typologies
Analyses of the 40 narratives revealed that all were of the chaos type, but elements of all three of Frank’s types of illness narratives (restitution, chaos, and quest) were present in a fourth of the narratives—more so in the parental narratives, with only a few of the proband narratives reflecting restitution and only one quest. However, the restition in the proband narratives was exclusivly related to the initial expectation that health would be restored. The narratives then became dominated by chaos, when health was not restored. The chaos in the proband narratives was mainly due to the suffering and loss (illustrations of life before the onset of illness and what had been lost: athleticism, employment and professional successes) and disorganization of the narrative with a multitude of difficult to connect symptoms. This disorganization is consistent with Frank’s description of chaos being “beyond words” [
19]. It is also possible that because they are undiagnosed, that the probands are concerned about “leaving something out” that may be the key to their returning to their previous lives resulting in their providing massive amounts of unrelated details and so chaos overtakes the narrative. Our findings suggest that living with an undiagnosed condition prevents the probands from being able to transition out of chaos to quest and the very nature of chaos prevents them from being able to clearly communicate their illness story.
In contrast, the chaos associated with the parent narratives was related to fear and uncertainty about their child’s future and an inability to make plans. Most of the research on parental narratives has focused on diagnosed childhood chronic illness or cancer and thus these experiences are different from those of parents of children who apply to the UDN [
22,
28]. For childhood cancer for example, although there is uncertainty about the future, there is a definitive diagnosis, a network of other parents who have children with the same diagnosis, and a plethora of support, resources, and possible next steps that are outlined by their healthcare providers. Bally describes that the chaos for parents of children with cancer occurred typically during the treatment phase with the transition to quest and restitution occurring after treatment [
22]. It is interesting that in our study, the parental narratives were found to be chaotic, but still had elements of both quest (finding new parenting strengths, focusing on the positive) and restitution (acceptance of a new normal), despite the lack of a diagnosis. The restitution and quest found in the parent narratives tempered the chaos associated with the fear and uncertainty that comes with having a sick child.
Clinical implications
The UDN clinical teams are put in the difficult position of having to make a decision regarding acceptance of applications from patients/parents who believe the network is their last hope for help. The decision is made almost exclusively by medical record review with very little, if any, interaction with the applicant prior to a decision. In general, if an applicant is not accepted to the UDN (due to different reasons, including the lack of objective findings), there could be very little closure for the applicant and the belief of not being heard may be reinforced. While indicating that acceptance was not appropriate, an acknowledgement of the pain and suffering that had taken place would be important. This may be helpful to some of the adult probands in their transition from chaos to quest or restitution- acceptance of a new normal. For parents of children with undiagnosed illness, reassurance that they have done everything they possibly could have for their child’s medical care and encouraging their role as an advocate for their child are important. It may also be important to consider inclusion of a social worker or another mental health provider to facilitate communication with the applicants.
Limitations of the study
This was a retrospective analysis of self- reported and open-ended patient/parent narratives and since it was not an interview, in which follow-up questions could be asked, there may be aspects of the illness story that could be missing. As these narratives were in a written format, the proband or parent would have had the opportunity revise or review their narrative prior to it being submitted and thus relevant information could have been lost/edited in the revision process. Additionally, there may be differences in an individual’s ability to write as opposed to verbally tell a story.
Acknowledgements
We are grateful to the patients and the parents who provided us with their perspectives of living with an undiagnosed disease.
The Undiagnosed Diseases Network:
Christopher J. Adams; David R. Adams; Mercedes E. Alejandro; Patrick Allard; Euan A. Ashley; Mashid S. Azamian; Carlos A. Bacino; Ashok Balasubramanyam; Hayk Barseghyan; Alan H. Beggs; Hugo J. Bellen; Jonathan A. Bernstein; Anna Bican; David P. Bick; Camille L. Birch; Braden E. Boone; Bret L. Bostwick; Lauren C. Briere; Donna M. Brown; Matthew Brush; Elizabeth A. Burke; Lindsay C. Burrage; Katherine R. Chao; Shan Chen; Gary D. Clark; Joy D. Cogan; Cynthia M. Cooper; William J. Craigen; Mariska Davids; Jyoti G. Dayal; Esteban C. Dell’Angelica; Shweta U. Dhar; Katrina M. Dipple; Laurel A. Donnell-Fink; Naghmeh Dorrani; Daniel C. Dorset; David D. Draper; Annika M. Dries; David J. Eckstein; Lisa T. Emrick; Christine M. Eng; Cecilia Esteves; Tyra Estwick; Paul G. Fisher; Trevor S. Frisby; Kate Frost; William A. Gahl; Valerie Gartner; Rena A. Godfrey; Mitchell Goheen; Gretchen A. Golas; David B. Goldstein; Mary G. Gordon; Sarah E. Gould; Jean-Philippe F. Gourdine; Brett H. Graham; Catherine A. Groden; Andrea L. Gropman; Mary E. Hackbarth; Melissa Haendel; Rizwan Hamid; Neil A. Hanchard; Lori H. Handley; Isabel Hardee; Matthew R. Herzog; Ingrid A. Holm; Ellen M. Howerton; Howard J. Jacob; Mahim Jain; Yong-hui Jiang; Jean M. Johnston; Angela L. Jones; Alanna E. Koehler; David M. Koeller; Isaac S. Kohane; Jennefer N. Kohler; Donna M. Krasnewich; Elizabeth L. Krieg; Joel B. Krier; Jennifer E. Kyle; Seema R. Lalani; Lea Latham; Yvonne L. Latour; C. Christopher Lau; Jozef Lazar; Brendan H. Lee; Hane Lee; Paul R. Lee; Shawn E. Levy; Denise J. Levy; Richard A. Lewis; Adam P. Liebendorfer; Sharyn A. Lincoln; Carson R. Loomis; Joseph Loscalzo; Richard L. Maas; Ellen F. Macnamara; Calum A. MacRae; Valerie V. Maduro; May Christine V. Malicdan; Laura A. Mamounas; Teri A. Manolio; Thomas C. Markello; Paul Mazur; Alexandra J. McCarty; Allyn McConkie-Rosell; Alexa T. McCray; Thomas O. Metz; Matthew Might; Paolo M. Moretti; John J. Mulvihill; Jennifer L. Murphy; Donna M. Muzny; Michele E. Nehrebecky; Stan F. Nelson; J. Scott Newberry; John H. Newman; Sarah K. Nicholas; Donna Novacic; Jordan S. Orange; J. Carl Pallais; Christina GS. Palmer; Jeanette C. Papp; Loren D. M. Pena; John A. Phillips III; Jennifer E. Posey; John H. Postlethwait; Lorraine Potocki; Barbara N. Pusey; Rachel B. Ramoni; Amy K. Robertson; Lance H. Rodan; Jill A. Rosenfeld; Sarah Sadozai; Susan L. Samson; Katherine E. Schaffer; Kelly Schoch; Molly C. Schroeder; Daryl A. Scott; Prashant Sharma; Vandana Shashi; Edwin K. Silverman; Janet S. Sinsheimer; Ariane G. Soldatos; Rebecca C. Spillmann; Kimberly Splinter; Joan M. Stoler; Nicholas Stong; Kimberly A. Strong; Jennifer A. Sullivan; David A. Sweetser; Sara P. Thomas; Cynthia J. Tifft; Nathanial J. Tolman; Camilo Toro; Alyssa A. Tran; Zaheer M. Valivullah; Eric Vilain; Tiphanie P. Vogel; Daryl M. Waggott; Colleen E. Wahl; Nicole M. Walley; Chris A. Walsh; Michael F. Wangler; Mike Warburton; Patricia A. Ward; Katrina M. Waters; Bobbie-Jo M. Webb-Robertson; Alec A. Weech; Monte Westerfield; Matthew T. Wheeler; Anastasia L. Wise; Lynne A. Wolfe; Elizabeth A. Worthey; Shinya Yamamoto; Yaping Yang; Guoyun Yu; Jing Zhang; Patricia A. Zornio