IntroductionRare diseases (RDs) affect no more than 1 in 2000 people [1], or 40 per 100,000 individuals [2]. Individually uncommon, they are collectively substantial: between 6000 and 9000 identified RDs impose major burdens on patients, families and health systems worldwide [13]. These complex, multi-system, often-debilitating conditions challenge achievement of several United Nations Sustainable Development Goals (SDGs) [4] (see Fig. 1).Fig. 1Full size imageA conservative view of the impact of RDs on five of the 17 Sustainable Development Goals.In low- and middle-income countries (LMICs), already facing multiple healthcare challenges [5,6,7], RDs expose a structural mismatch: systems largely designed around acute, single-system and well-characterised conditions are ill-equipped for chronic, multi-system disorders that frequently lack established care pathways. This misalignment exacerbates resource pressures and care complexity [8]. The estimated global RD prevalence of 3.5–5.9% [9], implies 263–446 million people affected, many with genetic origins [10], and with onset in infancy or early childhood. RDs are associated with reduced quality of life, impaired daily functioning, and reduced life expectancy [1]. Approximately 95% of RDs lack an approved treatment [11], and limited access to diagnostics (such as genetic testing) and available therapies is a major concern [12].Understanding RDs requires not only biomedical knowledge, but also insight into the lived experiences of affected patients, caregivers, families and service providers. Qualitative inquiry, which incorporates context and complexity [13], is ideally suited to illuminate these lived experiences. This begs the question: what qualitative RD research exists, and what is its scope?A search of multiple databases found relatively few reviews synthesising qualitative RD research. Among these, De Souza et al. [14]. provide the broadest overview, examining qualitative studies across conditions and participant groups from 2013 to 2018. Other reviews took narrower approaches, focusing on specific diseases [1516], symptoms [17], participant groups [18,19,20], experiences [2122] or issues [23].To extend this body of work, we conducted a narrative synthesis of original qualitative studies on RDs published between 2004 and 2024, including all participant groups. This approach moves beyond mapping the field to interpretively drawing together themes and patterns, comparing research contexts, and highlighting both shared experiences and disparities in focus and representation. A narrative synthesis was selected to enable interpretive integration across a large and heterogeneous body of qualitative research, prioritising depth and meaning-making over exhaustive identification. The purpose was to generate an integrated understanding of what is known about the lived experience of RDs, while identifying areas of convergence, persisting gaps and future directions for research.MethodThis project began as a scoping exercise, mapping qualitative research on lived experience in rare, genetic diseases (2004–2024), but evolved into a narrative synthesis due to the volume and heterogeneity of identified studies and the review’s interpretive aims. The analytic objective was to develop patterns of shared meaning (themes) across studies rather than exhaustively enumerate all items. The study therefore uses an iterative, reflexive synthesis approach to integrate conceptual findings across the literature.StrategySearches were run in Scopus, DOAJ, PubMed, Gale Academic One File, Science Direct, Clinical Key (Elsevier), SpringerLink, Wiley Online Library, Academic Search Premier, Ovid, and Biomed Central. Search terms combined rarity/genetic descriptors (e.g., “rare disease”, “genetic disease”) with qualitative methods and experience terms (e.g., “qualitative”, “interview”). Where title-only searches returned sparse results, searches were repeated to titles/abstract/keyword fields. Search combinations were applied across databases in a pragmatic rather than an exhaustive matrix structure, prioritising breadth and sensitivity.Considering lacking RD policy and strategic healthcare system approaches within LMICs [24,25,26], under-representation from these countries was addressed by supplementary searches combining the World Bank list of LMICs [27] with qualitative and rarity-related terms. Search terms and study counts per string are presented in Table 1.Table 1 Number of included studies per search string.Full size tableScreening and eligibilityRecords were screened by title/abstract and, where necessary, full text against the following inclusion criteria: original, peer reviewed, qualitative (or mixed-methods with extractable qualitative data) studies focused on the experiences of patients, caregivers, families, and/or service providers relating to rare, genetic conditions; full text available in English. For this review, rare conditions were defined as those with a prevalence of less than 1 in 2000. Duplicates, non-qualitative studies, abstract-only items, and reviews without original qualitative data were excluded.Data extraction and synthesisThe included studies were uploaded onto ATLAS.ti Web [28] for coding. Descriptive information (e.g. year of publication, participant details, methods) were coded and exported to Microsoft Excel (Microsoft Corporation) for numerical summaries and graphical representations.The interpretive analysis focused on all text presented under each study’s results or findings sections, encompassing both verbatim participant quotations and study authors’ interpretive commentary. Both were coded, since authors’ interpretations frequently extended or contextualised what participants’ own words conveyed, and omitting them would have discarded a meaningful layer of the qualitative account. Through close, iterative reading, codes were generated to capture key concepts, meanings and experiential accounts. These codes were progressively developed into candidate themes and refined through recursive engagement with the dataset. This is consistent with Braun and Clarke’s [29] own use of RTA as an interpretative review process, applying positioned, interpretative judgement to published literature rather than descriptive summary. Themes reflect interpreted patterns of shared meaning rather than mechanical aggregation. Consistent with this interpretive orientation, external literature was occasionally drawn upon in the Results section to illuminate patterns in the data, distinct from arguments extending beyond the corpus, which are reserved for the Discussion.Theme construction and refinement were led by the first author, with co-author interpretive feedback. Discussion between authors enhanced reflexivity and conceptual clarity, rather than establishing inter-coder reliability, in keeping with the epistemological underpinnings of reflexive thematic analysis [30].Data sufficiency and representativenessWhile this narrative synthesis was not designed to be exhaustive, the final corpus of 317 qualitative studies spanned a wide range of RDs, methods, participant groups and global contexts. Supplementary LMIC searches furthermore enhanced the representativeness of the data.The dataset was considered sufficient to achieve conceptual depth and to identify robust patterns of meaning.ResultsSearch resultsDatabase searches, as described in the methods section, returned 7982 potential articles. Applying the inclusion criteria, 317 studies were selected. While the search was extensive, it was not intended to be exhaustive; the aim was to synthesise and interpret findings across a large, representative dataset. More information regarding the search terms and the distribution of included studies are provided in Table 1.Results by locationOf 317 articles, 23 (7%) spanned multiple continents; the remaining studies were concentrated primarily in Europe (45%) and North America (32%). The reviewed literature therefore, reflects a strong concentration of qualitative RD research in high-income settings; however, geographic categorisation was based on participant populations rather than study origin, and as Europe represents multiple countries compared to the smaller number within North America, this distribution likely reflects differences in regional aggregation rather than underlying variation in research activity alone. In contrast to these high-income settings, studies including South American (2%) and African (3%) participants were quite rare. A relatively small proportion (8%) included participants from Australia and Oceania; however, this reflects the region’s comparatively small population and research base.Although these proportions are not intended to represent the global distribution of qualitative RD research, they nonetheless highlight a persistent imbalance in the geographical focus of published studies. In the present dataset, only 11 studies included African and 6 included South American participants, representing 330 and 47 participants respectively out of a total of 10,773 participants. Moreover, Africa was represented by just five (out of 54) countries and South America by four (out of 12), suggesting that the diversity of experiences within these regions remains underexplored.The representation of continents and various countries, within the included studies, involved in qualitative RD research can be viewed in Fig. 2.Fig. 2: Geographic representation of qualitative RD studies (2004–2024).Full size imageThe upper panel shows country-level distribution [67] of study participants, while the lower panel depicts continental representation expressed as percentages.Fifty studies (16%) involved participants from LMICs as defined by the World Bank classification, which encompasses low-, lower-middle-, and upper-middle-income economies. Where participant country was unspecified (e.g., international online recruitment), cases were excluded from LMIC/high-income country (HIC) tallies. Based on available country information, ~14% of participants represented in this synthesis were from LMICs, and ~86% were from HICs. Despite targeted supplementary searches, LMIC studies remain underrepresented within the qualitative RD literature analysed here.The geographical distribution of included studies invites a disquieting observation: the detailed picture of stigma, diagnostic delays, financial hardship and inadequate support documented here derives overwhelmingly from high-income settings. This underrepresentation, persisting despite deliberate efforts to include LMIC-specific studies, is itself a substantive finding. Where RD knowledge is produced, and whose experiences are considered worthy of formal documentation, are matters of power as much as methodology. This synthesis, however large, reflects a geographically partial account of what it means to live with an RD, and should be read as such.Data collection and analysis methods, participant characteristics and publication trendThe majority of the studies included in this review (69.7%) used semi-structured interviews to gather insights. 9.5% used focus groups and 5% a combination of both interviews and focus groups. A further 4.4% used questionnaires containing open-ended questions, while 3.2% used a case study approach, and 2.8% an ethnographic method. Other combinations of approaches each represented 0.3% of the methods used. Lastly, 3.8% of the studies reported using alternative qualitative data such as social media communications, narrative accounts, videos made by participants, support group videos, open written formats and personal journals.Regarding analysis, 37% reported thematic analysis, 21% content analysis, 9% grounded theory, 5% framework analysis, 5% interpretative phenomenological analysis, and 4% reflexive thematic analysis. About 8% did not name a specific method; however, at least 2% of these described processes consistent with thematic analysis.The study participants included the following groups and combinations of groups: caregivers only (30.8%), patients (26.6%), patients and caregivers (20.3%), caregivers, patients and service providers (service providers referring to healthcare and mental health care professionals, social support services, educators and patient organisations) (8.9%), service providers (6.6%), caregivers and service providers (3.5%), family members and patients (1.6%), patients and service providers (0.9%) and “other” (2%) (e.g. social media community group members, general public). One study (0.3%) sampled caregivers, patients, service providers, family members and the general public [30].Where gender was reported, 70% were female, 30% male, and 0.1% identified as non-binary. When isolating studies with a primary focus on caregivers, 82% of participants were female. The ratio of female to male caregivers from 2004 to 2024 fluctuated between 2:1 and 14:1; with the maximum number of female (caregiving) participants across studies being 868 (a 2024 Polish study, also including 57 males), and the second largest group of female caregivers at 108 (a 2023 study from the US, including 58 males). These two examples also constitute the two studies with the greatest number of male caregiver participants.Study sample sizes ranged from 1 to 925, with the majority of studies reporting between 8 and 20 participants. Twelve studies had 100 or more participants, which is unusual for qualitative studies [31]. The 317 studies synthesised, show a gradual increase in published qualitative RD studies over time (Fig. 3).Fig. 3Full size imageQualitative RD research output among the included studies (2004–2024).FociThe majority of the studies focused on caregiver experiences (21%), healthcare systems and access (17%), and patient experience (17%). Further foci included genetic testing, counselling and reproductive decision making (11%), disease treatment and management (10%), quality of life and psychosocial adjustment (6%), social impact and stigma (4%), diagnostic journeys and pathways (4%), family dynamics and relationships (4%), technology (3%), and information needs, seeking and sharing (3%).LMIC studies did not differ substantially in focus from HIC studies, most centring on caregiver, patient, or healthcare provider experiences of RD. Notably absent, however, were LMIC studies addressing genetic testing or the experience of new treatments.Rare diseasesAcross 317 studies, 113 specific diseases were named. It is important to keep in mind that many studies referred to more than one disease, not always within the same category of diseases. A full list with study counts and HIC/LMIC participant involvement can be found in Supplementary Table 2; disease-category counts appear in Fig. 4.Fig. 4Full size imageThe number of studies within the current synthesis involved in qualitatively researching diseases within each of the listed disease categories.Seventy-two studies (23%) had a broad focus on RDs; neurological disorders were the next largest category, citing 18 specific diseases plus a general neurodevelopmental grouping. Within the neurology category, Huntington’s disease dominated (39%), followed by fragile X syndrome (9%), neurofibromatosis (6%) and familial amyloid polyneuropathy (6%).The third largest category was lysosomal storage diseases, consisting of 11 distinct diseases. The most commonly reported lysosomal storage disease was mucopolysaccharidosis (all types, 28%), Gaucher disease (23%), and Pompe disease (15%).As per Fig. 4, the disease categories represented by the least number of studies were kidney/urinary diseases, cardiovascular diseases, endocrine/reproductive diseases, and rare cancers.Setting aside disease categories, the most referenced diseases, besides Huntington’s disease, were as follows: Cystic fibrosis (16 studies), Mucopolysaccharidosis (15 studies), Gaucher disease (12 studies), spinal muscular atrophy (11 studies), and Duchenne muscular dystrophy (9 studies).While Fig. 4 illustrates the distribution of studies across different disease categories within this dataset, Fig. 5 provides insight into the range of countries represented, divided into LMICs and HICs, for each disease category.Fig. 5Full size imageThe number of LMICs and HICs represented in qualitatively researching diseases within each of the disease categories.Lysosomal storage disorders drew participants from 19 countries (17 HICs, 2 LMICs). Neurological diseases involved the most LMICs (eight), including studies on familial amyloid polyneuropathy, neurofibromatosis, Rett, Angelman and fragile X syndromes. Dermatological studies uniquely showed equal HIC/LMIC country representation (four each), with albinism the most studied.Disease categories with no representation from LMICs were skeletal/connective tissue diseases, other specific disorders, undiagnosed diseases, and cardiovascular diseases.Themes and subthemesThe following themes were identified within the collective qualitative data: (a) psychosocial and emotional impact, (b) medical, healthcare and service provider experiences, (c) practical and financial aspects, (d) research, commercial and technological aspects, and (e) societal and cultural factors. A summary of these themes and the subthemes related to each can be viewed in Fig. 6 and will be expanded upon below. Where codes appeared in 50 or more studies, this is noted to provide a sense of how widely the issue was represented across the included literature. These figures are descriptive only and do not determine the interpretive weight or significance of the codes within the analysis.Fig. 6Full size imageThemes and related subthemes from the included 317 qualitative, RD studies reported on between 2004 and 2024.a) Psychosocial and emotional impactThis theme was applicable to both patients and family members and included subthemes which detailed the navigation of complex emotional and social experiences. Within this theme, the subtheme, Navigating Emotional Resilience, firstly represented the diverse means by which caregivers and patients sought support: mental health support (coded in 71 studies), support groups, and connecting with the larger RD community (coded in 78 studies). Secondly, it referred to the various strategies used to cope: denial, spiritual belief systems, ascribing meaning to the experience, and general coping mechanisms (coded in 109 studies; for example, exercise, positive thinking, mindfulness, desensitising oneself, gratitude, alcohol use, and trivialising the severity of a condition or situation [32,33,34,35,36,37]. Lastly, this theme is representative of the significant personal and emotional struggles which RD communities face: self-doubt, burnout, exhaustion, the processing of significant life events, caregiver responsibilities (coded in 67 studies), and a great variety of emotional experiences (various coded in 259 studies). Figure 7 provides more detail regarding the range and incidence of such reporting.Fig. 7Full size imageThe number of studies in this synthesis mentioning particular emotional reactions.Figure 7 warrants interpretive attention beyond the frequency counts themselves. That fear, anxiety and uncertainty rank highest is unsurprising in a field characterised by diagnostic odysseys and information scarcity, yet this reframes these emotions as responses to systemic failure as much as individual psychological states. More distinctive to the rare genetic disease context is the prominence of guilt, reported in relation to feelings of guilt or its relief in 67 of the included studies, and described in several of these studies specifically in relation to parents, where the particular burden of heritability, in which a parent’s love for a child is shadowed by a sense of biological responsibility. Most striking, however, is the presence of hope, which appears more than twice as frequently as hopelessness. That a single study [38] named disgust (in the context of epidermolysis bullosa) is a reminder of what safe research spaces can surface: emotions rarely voiced and entirely understandable.Notably, coping mechanisms were coded without evaluative judgement—alcohol use sits alongside mindfulness, trivialising severity alongside gratitude—not because these are equivalent strategies, but because the literature presents them as part of the same human effort to keep going. Viewed through a positive psychology lens, what emerges is less resilience in the classical sense and more endurance: the self as a finite resource being drawn upon, often to its limits.The subtheme, Redefining the Self, involved all aspects related to acclimating to the various aspects involved in having, or caring for someone with, a RD: adjustment (coded in 101 studies), normalising, dealing with mortality (coded in 51 studies), a loss of (or changes in) identity, the impact of a person’s stage of life (coded in 54 studies), as well as patient accomplishments.Of the three subthemes within the psychosocial and emotional impact theme, Redefining the Self is perhaps the most quietly significant. Where Navigating Emotional Resilience documents what people do to cope, Redefining the Self captures who people become in the process. The gradual reconstitution of identity following diagnosis, for patients and caregivers alike, represents a form of resilience less visible than active coping, but perhaps more enduring, consistent with broader theoretical work on identity reconstitution in chronic illness [39]. This is also where patient accomplishments appear in the data: moments of adaptation that resist being read purely as loss. In a body of literature necessarily weighted toward difficulty and deficit, these moments deserve particular attention.The final subtheme related to the theme of psychosocial and emotional impact is, The Social Experience of Illness. This theme includes both the social challenges and the importance of connection; more specifically: family and/or romantic relationships (coded in 142 studies), the impact of having a sibling with a RD, stigma and discrimination (coded in 115 studies), withdrawal and isolation (coded in 104 studies), socialising and community (coded in 88 studies), the choice of disclosing or not disclosing details about the disease, sexual identity and relationships, dependence vs independence (coded in 68 studies), having to miss out on experiences (holidays, activities or social events), and communication (coded in 116 studies).b) Medical, healthcare and service provider experiencesThis theme was applicable to patients, caregivers and the service providers who provide support and services to RD patients and families. Within this theme, the subtheme, Access, refers to the prolonged, frustrating, and even traumatic diagnostic journey RD patients often face (coded in 95 studies). It furthermore includes difficulties in accessing appropriate treatments, products, support, genetic testing, clinical trial participation, genetic counselling, and also locally available medical and psychological support (collectively coded in 86 studies).The subtheme of Quality, on the other hand, refers to healthcare interactions which include: positive and negative experiences of patients and caregivers of healthcare professionals (coded in 133 studies), service provider experiences, perceptions and needs, as well as the coordination of care (or lack thereof) (coded in 73 studies). Reflexively, the lacking care coordination described across studies appeared as a recurring pattern, suggesting that difficulties in coordination may reflect the limits of healthcare models primarily oriented toward acute and well-defined conditions.Navigating RD healthcare can feel markedly uneven, with outcomes shaped not only by access to the appropriate specialist, but by the chance of encountering the “right” clinician. Drawing on therapeutic practice, where the quality of the therapeutic relationship is itself a primary mechanism of change, the clinician-patient match strikes as particularly consequential in this context. Notably, the most important healthcare provider for a family is not always the most specialised: a few studies [40,41,42,43] documented the significance of a generalist who simply took notice, and took it upon themselves to learn. In RD, where specialist choice is severely limited, relational attentiveness may be among the most valuable and least acknowledged clinical resources available.Within the subtheme of Illness, the following is included: symptoms and other effects of the disease (coded in 134 studies), decisions about care, treatment and decisions impacting the future of the patient (coded in 116 studies), the nature and effects of treatments, supportive products or interventions (coded in 76 studies), treatment or disease management compliance, patient experiences (coded in 54 studies), patient behaviours, mobility and accessibility, and positive experiences or effects of the disease.The last subtheme within this theme, System, includes aspects of both advocacy and support and includes the following: the role of patients, caregivers (coded in 73 studies) and service providers as advocates and/or experts, caregiver and patient needs (coded in 57 and 53 studies each), and the lack, impact and importance of accurate information about RDs, as well as the prevalence of misinformation (collectively coded in 204 studies).The relationship between information access and clinician-patient relationships is not captured fully by the subtheme structure, yet the two are better understood as a cycle than as parallel concerns. Where patients and caregivers lack accurate information, they become more dependent on clinicians—yet in RD, clinicians themselves are often unfamiliar with the condition, contributing to variability in recognition, diagnosis and guidance. The clinician-patient relationship thus becomes a critical site where uncertainty is either acknowledged and navigated collaboratively, or obscured through misdiagnosis and incomplete explanation, which is itself a form of misinformation. Where these relationships are poor or inaccessible, misinformation fills the gap.c) Practical and financial aspectsThis theme relates the financial, logistical and care challenges faced by the RD community. The most notable factor within this theme is that of occupational impact (coded in 137 studies), which includes caregivers experiencing tension due to taking many days’ leave or time off in order to attend to a child’s medical appointments or needs, the need to move from full time to part time employment due to caregiving responsibilities, or to leave employment entirely in order to care for a child full time—all of which have financial implications. Other factors within this theme, relating to finances, are: government grants and policies, the cost of medication, treatments, diagnostic tests, assistive devices and even trial attendance. General financial struggle was also coded in 55 studies. More practical aspects within this theme includes thoughts and motivations related to genetic screening, the physical impact of care on the caregiver (such as lack of sleep and muscle strain), difficulties related to health insurance and the associated administrative burden, difficulties related to transport, travel and distance to attend medical appointments, the educational impact on paediatric patients, and the challenge of transitioning from paediatric to adult care, both for the patient and the caregiver.The data here raise an unanswered, but important question: how many of these households are single-parent households? With 82% of caregivers being female, and pervasive occupational impact documented across 137 studies, who supports the primary caregiver financially, practically and emotionally? The reviewed literature notes the importance of family support, but rarely examines its presence or absence with much precision. This gap reflects a tendency to document the caregiver’s relationship with the medical system while leaving the interior of the caregiving household comparatively underexplored.It is also worth noting that these burdens are not generic to serious illness, but specific to genetic conditions: decisions about family testing, disclosure, carrier screening and genetic counselling ahead of future pregnancies add distinct layers of responsibility on top of everything else. Even routine tasks (transport, schooling and administration) carry greater weight when the condition is rare, poorly understood by institutions, and lacks established local care pathways. These patterns are echoed in more recent literature published after our search period [4445].d) Research, commercial and technological aspectsThis theme includes the following: the advantages and disadvantages of participating in research and emerging technologies, expectations and concerns related to research, the experiences of research participants, motivations for engaging in new interventions, and the role of pharmaceutical and commercial companies within the field of RDs.Participants’ fears around false hope and access following the conclusion of clinical trials, prompted wider reflection. Across both clinical and qualitative research paradigms, there is a risk that participants come to be understood primarily as a resource: valued during data collection, and then sidelined [46]. This dynamic is particularly acute in RD contexts, a pattern evident across the reviewed literature, where communities are small, trust is hard-won, and the distance between research and tangible benefit can feel very large.e) Societal and cultural factorsThis final theme includes the following: the impact of a disease’s rarity, power dynamics (between patients, caregivers and healthcare professionals), safety, cultural factors, charitable support, gender inequality and/or gendered caregiving roles, and the impact of COVID on the RD experience.Cultural factors were most often coded in LMIC studies (China, Jordan, South Africa, Turkey, Iran). Only three HIC studies addressed culture, each regarding minority groups (a) UK case of an arranged marriage [47], a German immigrant experience [48], and a US call for culturally competent care for African American patients [49].Reflexively, it is worth noting that the apparent concentration of “cultural factors” in LMIC or minority-group contexts may reflect the way in which culture itself is conceptualised within the reviewed literature, rather than an absence of cultural influence in Western settings. During the coding process, cultural factors were initially more readily identified in non-Western contexts, prompting further reflection on how Western biomedical and individualist frameworks are often positioned as culturally neutral and therefore less visible. This suggests an underlying assumption of these frameworks as the default, a tendency that has also been observed in global health scholarship [5051]. Naming this pattern also raises the question of how such observations are made and by whom, highlighting the ongoing need for reflexive awareness in how taken-for-granted cultural frameworks shape both the production and interpretation of qualitative data.DiscussionGeographic disparitiesThis synthesis reveals a persistent geographic imbalance in qualitative RD research: roughly three-quarters of studies included participants from Europe and North America, with Africa, Asia and South America far less represented. Considering all country mentions, research participation appeared to be heavily concentrated in HICs, with limited representation from LMICs. While geographic representation in this synthesis reflects participant populations rather than research origin, the underrepresentation of LMIC participants likely reflects broader structural inequities, including disparities in diagnostic access, research infrastructure, and inclusion in global research networks.LMIC-based studies did not diverge markedly in thematic focus; however, few addressed genetic testing, and none engaged with experiences of emerging or experimental treatments—absences plausibly due to structural barriers rather than lack of relevant experience. The literature documents, in considerable detail, stigma, multi-year diagnostic odysseys, financial hardship, and systemic neglect, and yet this picture derives overwhelmingly from the world’s most resourced healthcare systems. If these are the documented experiences of families in comparatively well-resourced contexts, one is compelled to ask what remains undocumented where those resources are absent. Underrepresentation persisting despite deliberate LMIC-specific search efforts points to deeper questions about where RD knowledge is produced, whose experiences are considered worthy of formal documentation, and what forms that documentation takes—including whether peer-reviewed academic publication is the most appropriate or accessible medium in all contexts.Research methodologiesSemi-structured interviews dominated the methodological landscape, with a smaller proportion utilising focus groups and other qualitative methods. While interviews have become “taken-for-granted” in qualitative research(32p.155), greater methodological variety would better serve the relational and experiential aims of qualitative inquiry in this field. Specifically, participatory research models, which seek to locate the power and ownership of research within the communities it is intended to serve, warrant far greater emphasis [52].The range of analytical approaches (thematic, content, grounded theory, IPA, reflexive thematic analysis) reflects the breadth of epistemological traditions within qualitative inquiry. No single approach is inherently superior; qualitative research has been described as an artform [5354], and method choice should align with epistemological commitments and research questions [31]. Of greater concern is the proportion of studies that did not explicitly name their method of analysis. Transparency in reporting analytical frameworks is a scholarly imperative which allows readers to evaluate the nature and depth of claims [3155]. This may reflect not only inconsistent reporting practices, but a broader tendency to undervalue or misunderstand qualitative methods, treating them as a loose gathering and presentation of quotations rather than as rigorous, structured approaches to enquiry in their own right [56]. As such, future research should prioritise explicit reporting.Conceptualising RD experienceThe five themes generated through this synthesis provide a substantive account of RD experience across a large and diverse body of literature.Across the psychosocial theme, what emerged was less a picture of resilience and more one of sustained endurance. The self, in this literature, appears as a finite resource drawn upon repeatedly and often to its limits. This matters for how support is conceptualised: if coping in RD is better understood as endurance than as active adaptation, then interventions designed around skill-building and positive reframing may be less useful than those oriented toward relief, rest, and the restoration of capacity. The subtheme of Redefining the Self, capturing the gradual and internally driven reconstitution of identity following diagnosis, represents the closest approximation to genuine resilience in this dataset—not as a technique to be taught, but as a process to be supported—and deserves particular attention in future psychosocial research.The medical and healthcare theme surfaced a problem that is both structural and relational. Accessing appropriate care in RD might be likened to a game of chance, not only in the sense of navigating toward the right type of specialist, but of finding the right person within an already narrow field. This apparent dependence on individual clinicians can be understood as a feature of RD complexity, and as a reflection of healthcare systems that are not structured to support the coordinated management of chronic, multi-system conditions. As a result, relational quality becomes a primary determinant of care experience. Where patients have little or no choice in who they see, the burden of relational responsibility falls largely on the system.The thematic framework itself also warrants critical reflection. During coding, cultural factors were most readily identified in non-Western or minority-group contexts, a tendency that revealed the limits of the analyst’s own cultural positioning rather than an objective feature of the data. Western biomedical and individualist frameworks operate as an invisible default: present everywhere, named nowhere [5051]. Future qualitative work in this field would benefit from treating culture as a universal analytic lens rather than a marker of difference applied selectively to non-Western experience.Advocacy and information needsAcross studies, advocacy and access to accurate, accessible information were central to how participants navigated life with RD. Advocacy emerged as a necessity and, at times, a source of empowerment, while reliable information shaped coping, uncertainty and engagement with care systems. In contrast, lacking information was associated with increased distress and isolation.The lack of accurate information and clinician–patient relationships should not be understood as independent challenges. Where reliable information is lacking, patients and caregivers become more dependent on individual clinicians; where these relationships are strained or inaccessible, misinformation is more likely to fill the gap. In a context where knowledge is often uneven and incomplete across both patient and professional groups, these dynamics form a reinforcing cycle.Although relatively few studies explicitly examined advocacy and information needs, their consistent presence across narratives suggests that knowledge and visibility are foundational to the lived realities of RD. Interventions that address information provision without attending to relational care, or vice versa, are therefore likely to have limited impact.Trends over timeA gradual increase in qualitative RD research from 2004 to 2020, and a sharp rise thereafter, likely reflects the elevated international visibility afforded by the 2016 UN General Assembly Resolution on RD [57], and the 2019 UN declaration on universal health coverage [58]. This growth may also be linked to broader developments in the RD field, including increased advocacy and visibility driven by patient organisations, as well as advances in genomic technologies which have improved the identification and diagnosis of rare conditions [9]. The early prominence of Huntington’s disease (15 of 21 related studies published between 2004 and 2010) is most plausibly attributable to it being the first disease-related gene mapped to a specific chromosome [59]; generating significant early research momentum.Gender disparities in caregivingSince 70% of RDs have paediatric onset [60], it is unsurprising that caregivers constitute the largest participant group. However, the pronounced gendered pattern in caregiving, with no clear trend toward greater equality despite broader social shifts, is striking.Considered alongside occupational impact, this extends beyond individual experience to questions of household economics and who absorbs the true cost of care. A clearer understanding of these household factors is needed to identify both unmet needs and potential points of intervention.Importantly, this burden is specific to genetic conditions in ways not typically captured in the broader chronic illness literature. Developing care systems that are responsive to RD caregivers requires acknowledging the full scope of these intersecting demands.ImplicationsThe significant geographic disparities identified through this synthesis, underscore the urgent need for more inclusive and contextually grounded research, particularly in LMICs. Despite representing the majority of the global population, these regions remain underrepresented, limiting understanding of context-specific challenges and perpetuating global health inequalities. Asia represents almost 60% of the global population [61], yet contributes only 11% of qualitative RD research participants; Africa and South America, representing 26% of the global population combined, contribute just 5% [61]. These disparities are further explored in Supplementary Fig. 1.Greater collaboration between HIC and LMIC researchers is essential to support more equitable knowledge production and contextually relevant policy and practice.The predominance of semi-structured interviews suggests a need for greater methodological diversity [56]. Participatory action research, ethnographic studies, and other creative alternatives can enrich data and offer more nuanced understanding of lived experience [62]. Future research should be guided by reflexive, context-sensitive approaches that align with the relational and experiential aims of qualitative inquiry [63].Although few studies explicitly focused on information needs, the widespread presence of misinformation highlights a critical gap. RD organisations are already producing and disseminating condition-specific resources; however, systematic efforts to collate and extend their reach, particularly where they remain scarce, are still needed. This has direct clinical implications: fear, anxiety and uncertainty, the most prevalent emotional experiences identified in the reviewed literature, are often rooted in diagnostic ambiguity and informational absence. Psychosocial support that does not engage with these structural conditions, risks offering comfort without meaningful relief. Information provision, diagnostic clarity and care coordination should therefore be considered foundational to psychological wellbeing.These gaps reflect the broader fragmentation of care documented across this review. Biomedical systems, largely designed around acute, diagnosable and relatively common conditions, are poorly equipped for RDs, which are frequently chronic, multi-system and poorly understood by most clinicians. A more holistic model coordinating across specialities, centring the patient as expert, and integrating psychosocial alongside medical support may be better suited to this population’s needs [64].The pronounced gender disparity in caregiving, with 82% of caregivers being female, warrants further investigation. Because household context remains underexamined, it is not yet clear how caregiving burden is distributed within the home. Interventions should account for these structural realities, while also recognising that the burdens described here are often specific to genetic conditions. Experiences such as guilt, particularly among parents who perceive themselves as the source of their child’s condition, point to the need for therapeutic approaches that extend beyond general chronic illness models.At the same time, the prominence of hope across studies suggests an underutilised clinical resource. Within a positive psychology framework, hope is not a passive emotional state but an active orientation—one of twenty-four empirically identified character strengths whose deliberate cultivation has demonstrated therapeutic value [65]. Interventions that attend not only to distress, but also to existing strengths within RD communities, offer a meaningful direction for research and practice.Taken together, these findings suggest that the RD experience, as currently documented, is geographically partial, methodologically narrow, and shaped by assumptions that often remain unexamined. Addressing this calls for a reorientation toward underserved communities, investment in LMIC-inclusive research, care systems that recognise the relational and gendered realities of caregiving, and approaches to psychosocial support that are structurally informed as well as therapeutically responsive. The question is not only what we know about RD experience, but whose experience has shaped that knowledge, and whose remains unheard.Limitations and future researchSeveral limitations are acknowledged. The synthesis was restricted to English-language, peer reviewed academic literature, necessarily excluding regions where English is not the primary academic language and omitting grey literature—including reports and publications produced by patient organisations, charities and RD advocacy groups—which may contain qualitative experiential data not captured here. This is a limitation of particular relevance given the central role that community-generated knowledge plays in the RD field, especially in LMIC contexts where formal academic research infrastructure may be limited. Despite targeted efforts, LMIC representation remains low, and the findings cannot fully capture the experiences of RD communities in these regions. Contextually grounded, country-level studies focusing on LMIC settings and drawing on grey literature alongside academic sources would offer more nuanced insight into how structural factors shape lived experience in ways this synthesis can identify but not fully illuminate.While 113 specific diseases were represented, there are between 6000 and 9000 different RDs, meaning that this review has captured at most 1.9% of the potential RD experience. Continued work is needed, with increased focus on underrepresented conditions, such as Harlequin syndrome, Haddad syndrome, Carpenter syndrome and Meckel syndrome, among thousands of others. Disease-specific searching might have marginally increased coverage of particular conditions, but would have skewed the review toward conditions with larger research communities, which runs counter to the study’s intent. Grouping diseases into categories, as in Fig. 4, offers one pathway toward greater representation.The extent to which themes documented here, including caregiver burden and the gendered distribution of care, are reflected in RD policy remains an open question. Further research might also explore whether the pronounced gender disparity in caregiving is specific to rare genetic disease contexts or reflects broader societal patterns, including comparisons with caregiving in other chronic and age-related conditions.ConclusionThis narrative synthesis offers an expansive qualitative account of RD experience, drawing on 317 studies spanning two decades, and encompassing the perspectives of patients, caregivers and service providers across diverse geographic and cultural contexts. And yet, in a field defined by absence—of diagnosis, of treatment, of information, of understanding—the most consequential finding may be the scale of what remains undocumented. The dataset resembles a puzzle with more than half its pieces missing: the outline of the global RD experience is visible, but its full complexity cannot yet be seen. The experiences of families across Africa, Asia, South America, and the broader LMIC world remain largely unrecorded in the formal literature, not because they are absent, but because the systems that produce and legitimise knowledge have not yet turned sufficiently toward them.As explored in Fig. 1, RDs pose an easily underestimated challenge to achieving the UN SDGs [4], impacting poverty, health, well-being, education, gender inequality, and economic growth, even in HICs [66]. Without targeted efforts, disparities in these areas will likely continue to grow. The authors advocate for expanded qualitative RD research inclusive of LMICs, not only to fill identified knowledge gaps, but to address the far-reaching social and structural effects of RDs, and foster partnerships that can lead to meaningful improvements in care, policy and equity.As Baynam et al. observed, “To advance the diagnosis of diseases that affect indigenous people, it is necessary to listen to their voices”(47p.189). This principle must extend to all marginalised communities globally, to ensure that the next synthesis of this kind tells a fuller, more equitable, and more complete story.