Introduction

NKX2-1-related disorders (NKX2-1-RD), also known as benign hereditary chorea, is a rare disorder whose prevalence is unknown, and only about 120 diagnosed individuals worldwide have been described in the literature (Patel and Jankovick, 2023). This disease, resulting from pathogenic variants or deletions in the NKX2-1 gene, is characterised by choreiform movements at early stages, along with endocrine and respiratory abnormalities, such as hypothyroidism and neonatal respiratory distress (Carmona-Hidalgo et al. 2024; Liao et al. 2021; Nou-Fontanet et al. 2023). Other symptoms that may also occur in these individuals include tremor, myoclonus, dystonia, ataxia, sensorineural hearing loss, hypotonia and motor developmental delay, attention deficit and hyperactivity, hypodontia, short stature and psychiatric, cardiovascular and genitourinary abnormalities (Liao et al. 2021; Nattes et al. 2017).

Although the onset and progression of these symptoms are highly variable, they typically begin in childhood or adolescence and progress into the second decade, when they remain stable or remit (Carmona-Hidalgo et al. 2024). It is observed in clinical practice that individuals present difficulties in daily activities such as sitting, walking, or writing. However, there is still no evidence in the literature describing these problems. Therefore, there is a need to capture an in-depth and nuanced examination of challenges faced by this population.

In this context, the European Reference Networks on Neurological Diseases (ERN-RND) and on Rare Endocrine Conditions (Endo-ERN) with the support of the Andalusian Health Technology Assessment Area (AETSA), are developing the first clinical practice guideline (CPG) that will include recommendations as well as information to promote health autonomy and assist individuals and caregivers in managing this condition (Keinki et al 2018; European CHS Network, 2012). Thus, it is important to understand the individuals and their caregiver’s concerns, expectations and life circumstances (Llewellyn-Thomas and Crump, 2013).

Considering the above, the aim of this study was to explore the impact of the NKX2-1-RD on daily activities and the quality of life, as well as the needs related to healthcare services and their preferences, in order to avoid their omission from the CPG and accompanying patient information booklet.

Methods

Study design

This exploratory qualitative study was conducted by combining a focus group and five semi-structured interviews to ascertain the values, social services and healthcare preferences, and information needs of the individuals and their caregivers, as well as their perceptions of different health-related issues and their perceived quality of life. The study protocol was designed following the Qualitative Protocol Development Tool of the Health Research Authority (2018) and was published elsewhere (Martín-Gómez et al., 2023). The findings of the study are reported in accordance with the Standards for Reporting Qualitative Primary Research (Levitt et al. 2018) and the Consolidated Criteria for Reporting Qualitative Research (COREQ) (Tong et al. 2007).

Sampling and recruiting

Eligible participants were individuals affected by a NKX2-1-RD, caregivers, or representatives of the target individuals of legal age who were able to give informed consent and communicate effectively (orally and in writing) in English, French, German or Spanish.

The sampling strategy was based on what is known as theoretical sampling in qualitative research (Farrugia 2019). Twelve participants were recruited: five participated in the focus group, five were interviewed, and two finally declined to participate.

The research began with a focus group to broadly explore the pre-determined topics. This was followed by semi-structured interviews to delve deeper into these topics and to verify the consistency of the themes, both those identified in the focus group and those initially proposed. A methodology combining focus groups and interviews has been employed in prior qualitative research on rare diseases (Liu et al. 2023, Martin et al. 2024, Plackowski & Bogart, 2023).

Data collection

Data collection was conducted between April and September 2022. Both the focus group and interviews were performed virtually via the Microsoft Teams Platform. The rationale for conducting the study virtually was to facilitate the participation of individuals residing in different geographical locations and to mitigate the risks associated with the ongoing COVID-19 pandemic. The duration of both the focus group and interviews ranged from 40 to 80 min. The audio and video were recorded; except for one interview, which was only audio recorded at the request of the participant.

Given the European dimension of the project, the study included a focus group with participants fluent in Spanish, as well as semi-structured interviews with participants fluent in English, or French. Both the focus group and the interviews were conducted by the same researcher, who is fluent in both Spanish and English. For interviews conducted in French, a qualified interpreter with a research background translated the conversation between the participant and the researcher. The interpreter signed a confidentiality agreement to ensure participant privacy. A German interpreter was also available to facilitate the participation of German-speaking participants. Ultimately, no German participants were enroled in the study.

A structured script, based on literature on NKX2-1-related disorders and rare diseases, was developed and refined with input from clinical and qualitative research experts. It was used to guide the focus group and semi-structured interviews. Following the inductive nature of grounded theory, this script was expanded to include information provided by previously interviewed participants, ensuring that all relevant topics were discussed, as outlined in the study protocol (removed to maintain the blind review).

The broad topics were: (1) living with a NKX2-1-RD; (2) the care process and (3) information needs.

Data analysis

The focus group and the semi-structured interviews were transcribed verbatim. Transcripts were analysed using the NVivo V.12 software package by QSR International (Lumivero 2024). Thematic analysis informed by selected principles of Grounded Theory (Glaser & Strauss 1967) was the approach for the analysis of the transcripts. While our study draws inspiration from certain Grounded Theory techniques—particularly the use of constant comparison and inductive coding—we did not aim to construct a formal theory. Our analysis follows the structure of thematic analysis as described by Braun and Clarke (2006), with adaptations to enhance conceptual sensitivity through iterative data engagement. In this way, a deductive component was used, based on themes previously identified by the clinical and research staff involved in the CPG (those that pertain to the structured script), along with an inductive analysis following a grounded theory approach, where data was coded iteratively to capture emerging themes. Two researchers (XXX—removed to maintain the blind review) independently analysed the transcript of the focus group and two semi-structured interviews, and categorised the elements identified by the participants in topic proposals. Each topic consisted of a collection of speeches describing the same situation or issue. In this manner, an open code was developed, including the coding of speeches on similar subjects under the same theme. Then, each topic was reviewed and grouped together into larger units of meaning. After establishing the final coding scheme, each researcher conducted an independent analysis of all transcripts. Disagreements were resolved through consensus. Through this iterative process the themes were identified.

Given the small and heterogeneous sample, we did not quantify theme frequencies, as the analysis aimed to capture the depth and diversity of individual experiences rather than prevalence.

Reflexivity

In this exploratory study, we adopted an approach based on grounded theory with a tabula rasa perspective, meaning that we approached the data without preconceived notions or hypotheses about the participants’ experiences. This perspective allowed us to remain open to new insights and emerging categories, rather than fitting the data into pre-existing frameworks. While we acknowledge that this is not the most commonly adopted reflexivity paradigm today, we considered it the most appropriate given the lack of prior literature addressing the experiential aspects of the phenomenon under study.

At the level of interpersonal reflexivity, in both the focus group and individual interviews, we framed participants as experts in their own experiences, whether they were patients or family members, explicitly stating this at the beginning of each data collection process. This positioning facilitated deeper access to the experiences we aimed to explore.

From a methodological perspective, the exploratory nature of the study and its potential impact on the development of a European CPG led us to adopt an approach that not only allowed for the identification of new aspects but also enabled iterative exploration as data collection and analysis progressed.

Contextual reflexivity refers to the process of critically considering how the specific social, cultural and healthcare contexts of participants might influence both their experiences and the interpretation of the data. In this study, it was particularly important because our participants came from different countries across Europe and the U.S., implying variations in access to healthcare and social services that could influence their experience of the disease or caregiving.

Additionally, we reflected on how the study itself might impact the context: in the focus groups, interaction among participants fostered social support networks, while participation in the research provided them with knowledge about the development of the guideline, potentially enabling them to inform their clinicians about its existence and relevance.

Results

Participants characteristics

The focus group included four women and one man, all relatives of children and adolescents with NKX2-1-RD, from Spain. Five interviews were conducted with three women and two men from United Kingdom (n = 2), France (n = 1), The Netherlands (n = 1) and North America (n = 1). Participants were two mothers (one of whom lost her child) and three adults with the disorder; two of them also had affected children.

The analysis identified five themes: (1) diagnostic-related issues; (2) daily life and quality of life; (3) psychological and psychosocial factors and (4) healthcare and psychosocial services, including availability, use and needs; and (5) communication with healthcare professionals and information needs.

Diagnosis-related issues

Participants emphasised diagnostic challenges marked by multiple hospital visits, specialist consultations and tests. One adult patient recalled being initially diagnosed with cerebral palsy and seeing “many different hospitals, many different doctors,” until a paediatric neurologist identified a genetic disorder inherited by her child (P6, adult patient and carer of a 15-year-old patient). Another carer described a series of misdiagnoses—from Ehlers-Danlos to suspected Friedreich’s Ataxia, which was ruled out after MRI, genetic workup and lumbar puncture—before receiving the Benign Hereditary Chorea diagnosis (P10, carer of a 5-year-old patient). Misdiagnoses such as cerebral palsy, Ehlers-Danlos and Friedreich’s Ataxia were common. Time to diagnosis varied widely, from 3 years (“When the kid was 6 months old we started to notice… until when he was 3 years that we got the diagnose” P2, carer of an 8-year-old patient) to 18 years (“From 12 to 18 years old he tried to discover what was happening … then I was diagnosed” P7, adult patient (28) and carer of a 2-years-old patient).

Daily life and quality of life

The symptoms of NKX2-1-RD notably impact quality of life for patients and their carers, especially chorea-related walking difficulties and frequent falls. One carer recalled “many falls (…) it was a constant tug on your arm” (P3, carer of a 13-year-old patient), while another described how “constant falls (…) lead to damage to the knees” and frequent sprains requiring bandages (P4, carer of an 11-year-old). Gait abnormalities were also noted: “very wobbly(…) hyperextension in his legs (…) trips and falls” (P10, carer of a 5-year-old).

Also related to the body movements caused by chorea, individuals found it very difficult to sit still, even when seated-as one carer noted ““his body also moves a lot in the chair” (P5, carer of a 6-year-old patient). Task like pouring liquids and carrying objects are also challenging (“the sort of pouring liquids and carrying things” P6, adult patient and carer of a 15-year-old patient), and in more severe cases, individuals have suffered injuries such as sprains (see above P4) or even dislocations: “I had to have surgery because of the movements. I have dislocated my shoulders a thousand times” (P7, adult patient (28) and carer of a 2-years-old patient).

Lack of stability and coordination affected fine motor skills such as writing, eating and dressing, often slowing or preventing these tasks: writing “takes him longer” (P2, carer of an 8-year-old patient), is “slower… not pretty but legible” (P3, carer of a 13-year-old patient), or impossible on devices (“I cannot write in the computer or phone either” P7, adult patient (28) and carer of a 2-years-old patient). Dressing was also slowed down, as one adult patient explained: “I can do it, but I’m very slow, so with buttons, it takes much longer” (P7). Eating was also affected; one carer noted her child “still tends to choose to eat with her hands… can’t use a normal glass and still knocks over plates” (P10, carer of a 5-year-old patient). Motor problems extended to mouth and throat, causing speech and swallowing difficulties: one child “did not know how to speak” at age 3 (P5, carer of a 6-year-old patient), while an adult described struggling with certain letters despite 15 years of speech therapy (P8, 28-year-old patient), and another carer confirmed “even her swallowing is affected” (P10).

Urinary incontinence, present since childhood for some, also reduced quality of life: one adult reported “stress incontinence and urge incontinence… since I was about 6 or 7 years old” (P6), another noted needing bladder doctor visits from ages 4 to 16 and the urgency “reduces quality of life” (P7).

The NKX2-1 mutation could affect respiration, limiting activities like stair climbing: one adult must “stop and rest… [and was] out of breath” for about 10 years (P6); as a child, another “would quickly get out of breath” when running (P8).

Prolonged sleep was common, with needs exceeding norms: “I could sleep anywhere, anytime and still have a full night’s sleep” (P6), and a child “sleeps 12 hours a night (…) then naps two hours after school” (P10).

These challenges also affected social aspects like holidays. One family shared difficulty travelling after four years due to the illness and lack of appropriate travel insurance, as “insurance companies do not understand it and it does not fall into any categories” (P6).

Strategies for overcoming the day-to-day difficulties

The condition reduced individuals’ autonomy in many aspects of daily life. Nevertheless, participants described various strategies to cope with these limitations. To improve stability and reduce involuntary movements, several aids were mentioned, such as orthopaedic boots, Lycra suits, gloves with weights and morning elliptical workouts. For example, one participant explained that “orthopaedic boots help the ankle stability,” and wearing a Lycra suit under clothes “really helped her stability in the early years so she could sit and write” (P6). Another reported that “gloves with weights (…) make a big difference but you can’t wear them all the time” (P10). Similarly, regular elliptical exercise “helps [him] walk much better”(P2). To prevent falls at home, caregivers implemented adaptations such as handrails, suction grips in the showers and padded stairs. As one caregiver described, “we put a lot of railings all over the house([…), doorbells in all the bathrooms so that she can get our attention” (P10, carer of a 5-year-old patient). For outdoor mobility, families encouraged children to learn to ride a bike or similar alternatives like hand tricycles. While some children managed to ride a bike at age 5 (P5) or 12 (P3), others were unable to do so (P2). One participant shared that “with the bike, it is what he runs with, because he knows that it is what he can really move with” (P5), while another highlighted a hand-operated device: “somehow he can coordinate that and he does it really well (…) it’s amazing how fast it goes” (P10).

Psychological and psychosocial factors

Comparison with general population and disease awareness

A recurring theme among adult participants—whether patients or caregivers—was the tendency to compare themselves or their children to peers without the condition, especially in relation to developmental milestones. Writing, dressing, or walking were often mentioned as activities that took longer or were performed more slowly, reinforcing a perceived difference from others. As one caregiver explained: her daughter “still cannot write,” “still falls,” and “cannot do a lot of things that kids her age can do” (P10, carer of a 5-year-old patient). In more extreme terms, another caregiver reflected that her deceased child “could not live like a normal kid, play in school or anything” (P9, carer of a paediatric patient who died as an infant).

However, this perception was not fixed. Some participants expressed moments of normality or typicality, often when their symptoms were less visible or when they were able to keep pace with others. One adult patient described: “I feel like any other person, I do not feel different,” although she acknowledged that, as a child, “I showed certain delays in walking” and “didn’t walk well until I was 5 or 6 years old” (P8, 28-year-old patient). Another adult patient similarly remarked on her pregnancy: “I obviously got tired and breathless more than the average person. But kind of, I guess, to be expected to have a movement disorder” (P6, adult patient and carer of a 15-year-old patient).

These comparisons also marked the moment when children began to realise that something was different about themselves. Caregivers reported that as children age and engage more with peers, they become increasingly aware of their limitations. One caregiver noted that her daughter, now 11, was more psychologically affected: “When they are kids, the game they play is a lot of running (…) and she gets overwhelmed, because she can’t” (P4, carer of an 11-year-old patient). This awareness was echoed by adults recalling their childhood. “Since I was little, I knew I had a disease,” one patient affirmed, “but of course I did not know the name of the disease (…) not until I was 8 years old” (P8, 28-year-old patient).

Social interaction and perceived support

As discussed above, children became aware of the disease through interactions with peers. In these social contexts, other challenges associated with the condition—such as difficulties in mobility and speech—often became apparent, hindering socialisation and generating negative feelings like frustration or lack of self-confidence. For example, one adult patient explained how “it’s very difficult to feel confident enough to go out to places and physically get to places,” although she noted that family and close friends “do help us massively with getting around” (P6, adult patient and carer of a 15-year-old patient). Another participant shared how, as a child, “I could not talk properly, which hurts when people say, ‘Oh, can you state it again, please’. It was frustrating,” adding that even now, “when I am tired and cannot talk properly, instead of going out and socialising, I prefer to stay at home. It is easier that way” (P7, adult patient (28) and carer of a 2-year-old patient).

Despite these limitations, the support of family and friends was frequently highlighted. While patients acknowledged that making friends can be more difficult, they also emphasised the value of attending mainstream schools to support social integration. One participant noted that her daughter, who attends a mainstream school, “has really good social group who look after her,” contrasting with her own experience: “I had to go to a special school for people with disabilities” (P6, adult patient and carer of a 15-year-old patient). Similarly, another adult patient stated: “It is more complicated to have friends when you are different, that is clear, but with time it got better and today everything is going very well. I have friends, yes” (P8, 28-year-old patient).

Healthcare and psychosocial services: availability, use and needs

Healthcare

In general, healthcare, understood as healthcare provided universally at no or low cost to the patient/constituent, in the different countries are considered insufficient to address all aspects of the condition under study. In the UK, long waiting times and limited funding were criticised: “We wait months to get a test… during that time there is deterioration”. In Spain, some families turned to private specialists to access necessary care: “My son goes to a physiotherapist, but it is private”. In North America, even with insurance, the high cost of medical tests was a major burden: “In a month, we had up to $6,000 in bills after insurance”

Psychological therapy

While carers of younger children generally did not perceive a need for psychological therapy: “My son has physiotherapy twice a week, but not a psychologist—I do not think he needs it” (P2, carer of an 8-year-old patient)—this perception changed as children grew older. Relatives of adolescents often emphasised the importance of therapy, particularly to build confidence and emotional resilience: “We are going to therapy every two weeks to help her build self-esteem, empower her, and learn to set boundaries” (P4, carer of an 11-year-old patient). However, some raised concerns about therapists avoiding the topic of illness: “I asked the counsellor if we could talk to my daughter about how she feels about her illness … but I think the therapist was hesitant” (P6, adult patient and carer of a 15-year-old patient). Similarly, some adult patients expressed interest in psychological support despite not having accessed it: “I have never been to the psychologist, but it would be interesting” (P7, adult patient and carer of a 2-year-old patient).

Associations and groups of patients

Participants reported no knowledge of existing patient associations specifically for NKX2-1-RD in their respective countries, but expressed that such an organisation would be highly valuable: “If there was a group to analyse Chorea, a defined group, I would definitely join” (P7, adult patient and carer of a 2-year-old patient). Some mentioned broader support networks, such as SWAN in the UK, which provide psychological support and peer connection for people with undiagnosed conditions. As one participant explained, “It’s basically a forum so that we can all talk openly about different things. That has been probably the best hope of mental health wise for me” (participant anonymised to prevent identification). Social media groups were also considered useful for learning about the disease and connecting with others in similar situations.

Communication with healthcare professionals and information needs

Participants generally described communication with healthcare professionals as adequate and close, although most noted a lack of specific knowledge about the condition. As a result, they often felt responsible for informing their doctors themselves or engaging in a two-way exchange, such as “I was informing the neurologist” (P5, carer of a 6-year-old) or being constantly asked “what do you think about this?” (P7, adult patient and carer of a 2-year-old). Still, the contact was described as accessible and personal, with one participant noting: “I can send an email to the doctor every time I need” (P6).

This lack of information led them to seek knowledge from other sources, including research articles, theses, online groups, or directly contacting authors: “I contacted one of the people who wrote that article” (P7), “I was looking everywhere” (P5).

A recurring concern was the uncertainty about the future—how the disease will evolve, its impact on autonomy, and even life expectancy. One carer worried “if he’s going to be able to drive” (P2), while an adult patient questioned: “Am I going to be stuck in a wheelchair?” (P7), or “if I am going to die of this disease” (P8).

In addition to medical concerns, participants also expressed the need for practical and legal information, such as how to apply for disability certificates or therapy support: “Knowing if you can request a certificate of disability, even aid for therapies (…) everything helps” (P4).

Finally, all participants agreed on the importance of having accessible, clear information in multiple languages to explain the disease to others, especially in new social or professional settings. For instance, a UK participant wished for “a very basic description” of the disease, as medical literature was hard to understand, while another from France noted the lack of translated materials.

We consider the findings to be meaningful and valuable and to provide relevant information about a little-studied population. Furthermore, once the CPG for which this study was conducted is developed, the process of adapting it to different contexts will provide an opportunity to ask more participants about their own experiences within their specific healthcare systems, thereby overcoming this limitation.

Discussion

NKX2-1-RD include a set of pathologies characterised by choreiform movements from an early age, along with endocrine and respiratory problems. The first CPG is being developed for these disorders by the ERN-RND, Endo-ERN and AETSA. The main aim of this study was to explore the impact of the disease on quality of life and the needs associated with healthcare services for individuals and their caregivers, including the insights in the aforementioned CPG.

The perspective of affected individuals needs to be considered when addressing any condition. However, in the case of rare diseases such as NKX2-1-RD, it is especially relevant due to the limited evidence available, and this is reflected in the methodological guidelines on the subject (Granja-Dominguez & Martín-Gómez 2024; Grupo de trabajo sobre implementación de GPC 2009; Guidelines International Network 2024). This can also improve patient satisfaction with the health services received, along with better informed and shared clinical decision-making (Pérez-Ramos et al. 2015).

This study has revealed some topics that are of interest to individuals, as well as their concerns and needs, and knowing them is essential in addressing their diseases. First, all individuals from the study got the final diagnosis after several years of tests and visits to different specialists, even in some cases after failed diagnoses such as cerebral palsy or Friedreich’s ataxia. This is in line with previous studies which suggest that in Spain and Europe there is a diagnostic delay between 4 and 10 years for known rare diseases, even though they should be diagnosed within a year (Ancochea et al. 2018; Benito-Lozano et al. 2022; Faye et al. 2024). This delay might result from limited knowledge about the disease or the presence of different symptoms that mislead the physicians to get the correct diagnosis and potentially affect the response to the treatment. Hence the need for CPGs such as the one currently being developed and to which this study contributes.

In the case of NKX2-1-RD, the delay in correct diagnosis could be due to the recent identification of the gene whose mutation causes the condition, which was just 20 years ago, in 2002 (Breedveld et al. 2002). Thus, it is important that physicians are aware of the latest available evidence on the pathologies, and the main symptoms and explanations of individuals to obtain the right diagnosis or to refer them to the correct specialists.

The study highlights that patients’ quality of life is severely impacted, primarily by chorea-related symptoms such as difficulties with mobility and balance, leading to frequent falls and injuries. Motor impairments also hinder activities of daily living, including writing, dressing, eating, speaking and swallowing. In addition, they highlight the complaint about urinary incontinence. This aspect is very revealing because it had not been considered by clinicians involved in the CPG, and was one of the topics that were added to the interview script during the data collection process. Because it was added, it was possible to see how this is an aspect that affects patients with NKX2-1-RD in general. These limitations contribute to feelings of low self-esteem, frustration and social isolation. Previous studies on Huntington’s disease have reported similar findings regarding the significant impact of chorea on quality of life, particularly in terms of daily activities and social interactions (Sherman et al. 2020). Interestingly, the study has also revealed the strategies and tools that patients use daily to manage these challenges. Future research should focus on evaluating the efficacy of these interventions specifically for this condition. These findings could support the integration of these strategies and tools into future care initiatives. As already known from previous studies (Carmona-Hidalgo et al. 2024a, 2024b; Nou-Fontanet et al. 2023), in addition to motor problems, the NKX2-1 mutation can also affect the respiratory and endocrine systems in some patients, although these issues have been reported as less impactful on daily life.

Throughout the study, it has also been shown how individuals tend to compare themselves with the general population, and how from these comparisons with their peers without the pathology, they become aware that they have a disease. Likewise, families of children and individuals who are the first in the family to present with this rare disease tend to compare themselves more with the general population, perhaps because of the normative developmental expectations they have. However, this does not occur as often in cases where individuals have children with the same pathology, probably because they have adjusted their expectations to their own experiences. It has thus become clear that the impact of the pathology goes beyond the physical symptoms, affecting also the routine and emotional state, something that has been previously described for other rare diseases (Gimenez-Lozano et al. 2022; Von der Lippe et al. 2017; Spencer-Tansley et al. 2022). It could be interesting to develop future lines of research in the psychology and wellness of individuals with rare diseases in the paradigm of Developmental Psychology. This could help evaluate the actual state, progress and needs at the different evolutionary stages of the population with the disease, which would facilitate the assessment of disease progression and the support they need (Smits et al., 2022). Moreover, this approach would provide the scaffold needed to grow up in the context of the pathology, as stated in the theories of Vygotsky and Bruner (McCleods 2024). It could also help to assess specific milestones at different life stages, such as pregnancy, speech development, or the walking onset. This approach could shift the focus away from comparisons to an idealised “normal” and towards understanding individual strengths and needs. This, in turn, could help dismantle prejudices and stereotypes associated with uncommon development. Psychological interventions to support individuals with rare diseases could also accommodate this approach, as is already done in other models to address paediatric-onset conditions. For example, with this developmental approach we propose, an intervention programme to address paediatric traumatic stress, they propose an adjustment to important transitional stages such as the age at which schooling begins, when children start to build social relationships or when important cognitive developments occur (Kazak et al., 2006). This study has demonstrated that, as patients age, the need for these interventions becomes increasingly evident. Therefore, these interventions stand out as an essential service that should be available to the individuals and caregivers of NKX2-1-RD and individuals with rare diseases in general. However, some studies performed on individuals with rare diseases have observed that most of them do not access the psychological support they need, mainly because it has not been suggested by the healthcare professional (Spencer-Tansley et al. 2022). Additionally, in many cases, they cannot afford private psychological therapy since it is not covered (Gimenez-Lozano et al. 2022; Spencer-Tansley et al. 2022). In this regard, EURORDIS (Rare Diseases Europe) have developed initiatives to increase the mental health and wellbeing of individuals with rare diseases (Eurordis 2024) that may provide a basis for enabling these kinds of interventions and research in the field.

Regarding healthcare received in general, the individuals from this study are satisfied with the attention they received from the healthcare providers; however, they feel more informed than the clinicians. Individuals and their families are very proactive looking for information to understand more about their disease, how it will evolve, and whether they will have health issues in the future, in accordance with previous qualitative studies done on other rare diseases (von der Lippe et al. 2017). The creation of networks of specialised clinicians could also promote the flux of information among regions and countries, increasing the knowledge about the disease among clinicians and making it more accessible to individuals and caregivers. The work performed by ERN-RND and Endo-ERN under the CPG development might begin a network of experts in NKX2-1-RD and could also encourage the creation of a patient association, given that participant stated that there is no such organisation at present.

They also complain about the lack of documents on the disease in plain language and in languages other than English. This study will help to overcome this demand, and their results will have a direct social impact since they will be used for the CPG that is in process and for the patient information leaflet that will accompany it, being part of an evidence set generated to inform this CPG. Previous work by the guideline development group includes a number of published systematic reviews on drug therapy for chorea (Nou-Fontanet et al 2023); screening and diagnosis, and treatment and follow-up on thyroid function (Carmona-Hidalgo et al 2024a; 2024b); and the clinical management of respiratory manifestations (currently under review), among others in preparation. In this regard, it is important to mention that the available recommendations documents do not include aspects from NKX2-1-RD individuals (Patel & Jankovick, 2023; Van Trotsenburg 2021) and therefore, this study also contributes to collecting some significant issues that will help healthcare professionals have a deeper understanding of the disease.

Limitations and strengths

Regarding the participants, they provided information on patients from a wide range of ages, from children to adolescents and adults, so data was collected from different developmental stages. However, it could be considered a limitation that only adults participated, both patients and relatives of patients. In future studies it would be very interesting to know first-hand the perspective of children and adolescents with the disorder, and also elderly if feasible. This could contribute in a more adjusted way to generate the necessary support in contexts such as school. Other aspect to considered is that individuals from different countries participated in the study, allowing a global perspective from their individual viewpoints. Nevertheless, they are mainly from Western and Central Europe and the Americas, which may bias the information regarding the services available in Eastern Europe, among other aspects of patients’ and carers’ experiences. Another aspect that could be considered a limitation is the small sample size. Nonetheless, the number of participants was determined considering that this is a qualitative study and that the condition studied is considered a rare disease by the European Commission (2024). Taking this into account, the study design provides sufficient informative power to extract preliminary conclusions based on the methodological approach proposed by Malterud, Siersma and Guassora (2021). Furthermore, the qualitative design of the study has allowed us to investigate aspects that are not possible with quantitative research. Since the topic script is modifiable, it has been possible to gather topics not originally included in the study, integrating the patient’s perspective into the data collection procedure. Specifically, it has occurred with the concern about urinary incontinence, which had not previously been contemplated either in the CPG or in the initial topic script. After a patient mentioned it, it was included in the script and was asked about by the rest of the participants. They confirmed that they had experienced similar issues. Furthermore, although theoretical saturation was not achieved, the rarity of the condition and limited participant availability prevented further data collection. Still, participants’ accounts were consistent despite the geographic and healthcare diversity of the sample. Additionally, we acknowledge that caregivers provided proxy reports of the children’s and adolescents’ experiences, which may not fully reflect their personal perspectives. This difference could influence the interpretation of findings related to patient-centered outcomes. Lastly, although translators were used for some interviews, and not all were native speakers of the participants’ languages, we took care to cross-check translations and review transcripts; nevertheless, it is possible that some nuances in participants’ expressions were lost.

In conclusion, these findings could improve clinical decision-making and the care received by NKX2-1-RD individuals, as well as help both adults and children explain the disease to the people they are in contact with.