2.1 Study Design

This qualitative study is part of the national multicentre study ‘Improving the clinical care for Genetic Rare disease: Observational Cohort Study’ (GenROC: REC22/EM/0274) [5]. We aimed to understand the lived experience of parents of children with GNDs to identify the needs, obstacles and barriers for families relating to their child's genetic diagnosis. To understand their experience, the first author undertook semi-structured interviews with parents of children with known GNDs aged 0–15 years. Interviews were based on a semi-structured topic guide that had undergone ethical approval as part of the wider approval process for the GenROC study [9]. The topic guide was informed by the relevant literature [4-8, 10-16] and developed with professionals and stakeholders in the area of rare disease, as well as the study's Patient Participant Involvement (PPI) group. The topic guide was presented to the PPI group (comprising five mothers and one father of children with GNDs, one young person with a GND, and one genetics family charity representative), who provided comments on the structure and content as well as the planned interviews. Particular feedback included that the guide needed to allow for time for parents to revisit their diagnostic journey and also that parents should be allowed to be interviewed together if they wished to do so. PPI strongly recommended online interviews for practical acceptability.

The interviewer was a senior clinical geneticist who has had training in qualitative research methods and no prior contact with the participants. All interviews took place online with participants in their homes using the video conferencing platform, Zoom. A child was present in one interview.

The topic guide follows a predefined structure but allows additional questions and emerging issues in the context of GNDs. This guide includes (1) an introduction of the study and interviewees, then focussed on (2) the families' pathway leading up to and during the diagnosis, (3) daily living with a GND and its impact on navigating healthcare, (4) what information families have been missing and how they have looked for this information and accessed it including areas of support and (5) if and how they utilise digital health and social media in this respect and (6) a chance for parents to discuss anything else that they felt was important (see Supporting File 1).

2.2 Participants and Sampling

Inclusion and exclusion criteria for participation in the interview were as for enrolment into GenROC [6], which were children aged from 6 months to 16 years with a confirmed diagnosis in a set list of GNDs living in the United Kingdom.

Parents completed consent to participate in the GenROC study, and of these, 91% agreed to being contacted about an interview.

We estimated that we would aim to interview 10–20 parents and purposively sampled participants from families recruited to GenROC to ensure maximum variation across the following categories: (1) postcode Indices of Multiple Deprivation (IMD) centile; (2) type of genetic disorders (Figure 1); (3) UK geography; (4) ethnicity; (5) children of differing ages; (6) foster and adoptive parents; (7) parents advocates, leads of support groups or charities; (8) fathers were actively recruited through the invite email which specifically highlighted that we were keen to hear from fathers if possible (as well as mothers), which increased our number of fathers included by four. We agreed that parents could request to be interviewed together as a couple, which enabled some of the fathers to take part and empowered them to be part of the discussion. The sampling factors were intentionally chosen to allow for demographic and diagnostic variation in the sample. We also used our clinical insight and expertise to select participants with specific characteristics, such as parents who are advocates/charity leads and foster carers, as we anticipated that they would provide strong dialogue to satisfy our study aims.

Parents were invited to take part by email. They were informed about the study using a Parent Information Leaflet, which had undergone ethical approval as part of the wider GenROC study [6]. Parents were required to complete an interview-specific consent form before the interview. Appointments dates and times for the interview were agreed upon via email. No participants refused to participate, nor did any drop out.

2.3 Data Collection

The interviews were conducted between November 2023 and March 2024. Interviews were conducted by the lead author, who is the chief investigator of the GenROC study. All interviews were recorded, transcribed verbatim and anonymised and combined with the interviewer's field notes for analysis. Transcriptions were imported into NVivo qualitative data management software (Release 1.71) for coding and data management. Using the concept of information power to inform the sample sufficiency, we expected that using a case analysis strategy with specific participants who would provide strong dialogue would satisfy our relatively narrow study aims [17]. After eight parents were interviewed, the process was paused to review the data and to develop and refine the coding matrix. We determined that we would continue with interviews until no new code categories were being generated and no new themes were created [18, 19]. No repeat interviews were undertaken.

2.4 Reflexivity Statement

K.J.L. (interviewer) is a senior clinical geneticist with particular expertise in caring for children with GNDs and with a background in paediatrics. She is also a mother of two neurodiverse children and has a rare disease herself. G.T.E. (second coder) is a non-clinical, experienced qualitative researcher with no genetics expertise. Both live in Bristol, the United Kingdom. G.T.E. is an experienced psychological and behavioural researcher and has conducted many qualitative studies and provided guidance for K.J.L., as this was her first qualitative study. K.J.L. has conducted multiple clinical studies into GNDs.

2.5 Data Analysis

Reporting of data has been performed according to COREQ guidelines [20]. Data were analysed following the principles of inductive thematic analysis based on an interpretive/constructive epistemological perspective to explore the lived experience of parents [18, 19, 21]. An iterative approach was used to develop an initial codebook informed by the aims of the study (deductive component). The first eight transcripts were coded by the first author, and additional codes that were not covered by the initial codebook were then added (inductive component). 20% of the transcripts were double-coded by the second author. All discrepancies were reconciled through consensus. The first author discussed her impressions and assumptions with the second coder reflexively. NVivo software was used to group codes, and these were refined following discussions between the authors. Methodological oversight was provided by the final author, who was also a non-clinical qualitative researcher.

3.1 Impact on the Family Around Receiving a Genetic Diagnosis

3.2 The Impact of Uncertainty, Lack of Data and ‘Rareness’

Professionals who are giving the diagnosis often know very little about the condition and simply direct parents to Facebook support groups. Professionals blame the large number of rare conditions for their lack of expertise (Q6).

Some parents are anxious that having a genetic diagnosis can result in a child's challenges being incorrectly attributed to that condition and not being correctly investigated (Q7).

Parents, therefore, need to pursue information that adds to their mental load. Some parents reported frustration around the lack of detail provided to them at diagnosis with particular respect to their child's specific genetic variant, which then hampers their self-directed research efforts (Q8).

Detailed natural history data for GNDs are often limited, with the pace of new data acquisition slow. This can lead to parental frustration and worry when their child develops a new problem and limits parents' ability to plan and manage expectations for their family and the future. Recurrence risks quoted to parents were unclear or differed between health professionals and the support groups/research. A parent described the devastation of having a second affected child following genetic counselling of a low recurrence risk. The general population has a limited understanding of GNDs. This places an additional burden of explanation on parents to extended family, friends and wider community. Some describe the frustration of people trying to suggest they have lived experience when they do not.

3.3 Relationship With Health Professionals

Parents are required to advocate for their child endlessly and feel continuously doubted by professionals which can be extremely hard, tiring and upsetting. Foster carers can face a higher threshold of belief by professionals who question how ‘well’ they know the child.

Parent-professional hierarchies and professional egos result in difficult interactions when parents present new data or question the clinician's opinion. Parents perceive that some professionals (particularly hospital consultants) don't like to be told what to do by a parent (Q9).

Parents may hear about possible treatments or therapies that children with the same GND are on, and this may be through their own research or through social media groups and connecting with other families. This may suggest to them their child should be receiving a treatment or therapy which they have not been able to access. Service pressures result in parents having to be more demanding than they would wish to be which is exhausting, and busy clinical environments can lead to a perceived lack of empathy (Q10).

Having a good relationship with the child's key paediatrician was reported as being an important support. Parents highly prized an egalitarian relationship with a doctor in which they were empowered to bring new information and questions and were listened to without judgement with time and space to talk (Q11).

Parents reported that their own education and work background sometimes impact positively or negatively on health professional attitudes towards them with examples being a biology teacher (who felt she was treated more as an equal) and a shop worker (who felt talked down to), respectively.

Parents would like to have a named clinical expert for their child's genetic condition who can coordinate care nationally; however, this is very variable as some conditions do not have one and for many the ‘expert’ is in another country. Parents may travel to attend the international family conference at considerable personal expense which would not be possible for many families and can be impossible with complex childcare needs and a lack of a wider family network to help. However, those who have accessed an ‘expert’ reported that it reduced their anxiety and resulted in them feeling better informed and able to support their child.

3.4 Parent Mental Health

Many parents described that having a child with GND along with lack of support has resulted in a significant deterioration in their mental health. This is exacerbated by a constant need to fight with professionals to access care and support for their child; in one case, this battle led to a social services referral. Professionals sometimes assume parents are overanxious which can cause an additional impact (Q12).

Managing children's challenging or unsafe behaviour is particularly difficult for families. Parents need to be constantly vigilant and cannot get respite, placing a huge demand on them daily (Q13).

4.1 Parent's Experience of Receiving the Diagnosis and the Impact of the Diagnosis on the Parents and Family

The diagnostic wait is difficult for families [10]. Access to genomic testing has improved in the last decade, but many parents still describe a period of time in which they knew something was not right with their child, but were dismissed by healthcare professionals, or they could not access the appropriate service. Even in cases where a diagnosis was made at a young age, parents report the lag time leading up to that diagnosis as being distressing. Frustration and distress associated with the diagnostic odyssey have also been reported in parents interviewed as part of an undiagnosed diseases programme [11]. Nonetheless, there is clear evidence in the literature and from our findings that parents consider a diagnosis to be enormously beneficial as it gives a reason ‘why’ and opens doors to services and support [4, 5, 10-12, 14, 22, 23]. Distress appears to be unavoidably related to the period of time when parents do not have an explanation or answers for their child's symptoms [4, 11]. It may be that some of this distress is not avoidable, as much of it relates to having a child who has problems, often unexpectedly. However, attempts to reduce waiting should be prioritised at all stages.

The lack of information in GNDs leads to distress and worry [5, 10], and this was apparent in the current findings. Most of the time, it is not possible to predict accurately where their child would fall in the long term compared to others, raising anxiety and making it difficult to plan. Raising the profile of adults with these GNDs and allowing them to become mentors and advocates (as has been done for another rare disorder) [7] may be a mutually beneficial strategy going forward as more children who benefited from exome sequencing diagnoses grow up (Figure 2).

Parents may feel alone despite receiving a diagnosis [4, 5, 12, 14]. Shared lived experience and peer support are beneficial for many parents [12]. This allows them to ask questions and find out information from other parents, including finding out about resources available for their children [8, 12, 24]. This was echoed by some of the parents in our study who reported that peer support groups can give you useful insight into options they had been unaware of [25]. Parents of GNDs can become socially isolated due to lack of understanding from society, complexity of their child's needs [12, 13, 26, 27] due to worry and shame related to their child's behaviour and people not being able to understand that their child had a complex underlying diagnosis [28]. A virtual peer support group circumvents these barriers and reduces social isolation [25, 29, 30]. The diagnosis discussion should include information about support groups and ideally signpost families to an appropriate group so that they are aware of these from an early stage (Figure 2).

A genetic diagnosis is not the same as any other paediatric diagnosis [8, 10, 14, 23]. A mixed-methods study of the lived experience of parents of children with CDKL5 deficiency disorder cited grief and an associated grieving journey in the context of receiving the diagnosis as a nearly universal theme amongst parents [8]. Our findings highlight that the ‘genetic-ness’ of the diagnosis had very specific impacts on parents. For instance, parents felt that the genetic diagnosis means that the condition can't be reversed, and it's not going to go away, and it removed the hope of it getting better. These findings were echoed in the Rare Minds 2024 survey [31]. They found that 41% and 85% of respondents felt having or caring for someone with a rare condition had negatively impacted their family relationships and their mental health or emotional well-being, respectively (Figure 2).

Our findings indicate that for some families and conditions, a genetic diagnosis removes hope [10]. It is important that professionals recognise the way this differentiates this type of diagnosis from others. Psychotherapeutic counselling should be funded specifically for families with genetic disorders, but currently is not available for most and is very rarely offered [31]. 96% of Rare Minds' respondents felt that it was important that mental health professionals had an understanding of rare conditions and how they can impact mental health. This agrees with our findings and we concur with the Rare Minds recommendation [31] that anyone impacted by a rare condition should receive psychologically informed ‘rare aware’ care (Figure 2).

A genetic diagnosis also has an impact on the wider family. The impacts for siblings and family life when having a child with any sort of complex medical condition or neuro-disability are well documented and include the stressors of managing emergencies, coordinating care, and advocating for your child and fighting the system [8, 10, 15, 16, 27, 28, 32]. Lack of time, socio-legal difficulties and organisational problems are significant barriers [13, 16, 33]. All parents in our study described some dissatisfaction (of varying proportions) with the healthcare system and professionals. They describe an endless battle to be believed and heard, to access the appropriate care, and to access specialist services. This impacts mental health and reduces their capacity to cope with additional challenges, as well as negatively impacting patient–professional relationships. A centrally coordinated pathway for GNDs with centres of excellence may reduce this burden for families and ultimately improve clinical outcomes (Figure 2).

4.2 How Parents Navigate Their Child's Care as a Consequence of the Genetic Diagnosis

Parents develop considerable expertise in managing their child's condition, and this can be both a burden and a source of self-fulfilment at the same time [8, 13, 16]. Our study shows that parents feel they become experts out of necessity due to the overwhelming need to know more and to try and understand what the future holds. However, some parents take a more active role in becoming experts. For some fathers in our study, becoming an expert allowed them to feel that they were ‘doing something’ active about their situation, which allowed them to cope better with the challenges. Parents should also be signposted to further options for education, explaining basic genetics to minimise their frustration in understanding the information (Figure 2).

It is important for professionals to provide parents with key information about the genetic diagnosis, including the variant details. Peer mentoring may provide a support mechanism in this regard, particularly for parents who wish to become more active as professional advocates [7]. Parents desire a national named clinical expert for their child's rare condition and consider this a priority. Implementation is challenging on a practical level given the number of different rare conditions, funding mechanisms and clinical setups. This point should be considered as a medium-term strategic priority for rare disease (Figure 2).

4.3 PPI Reflections

Our PPI group reported that our findings resonated very strongly with their lived experience. They recognised that professionals are doing their best in often difficult circumstances, but hoped these findings would drive improved practice. A member reflected on the significant burden of being an expert in their child's condition and the fight to be heard.

4.4 Strengths and Limitations

Despite our best efforts, the majority of participants were females. A strength of the study is that by agreeing that couples could be interviewed together, we increased the number of fathers who were interviewed. We also noted that whilst some fathers were initially reluctant to speak, and even initially remained off camera in one case, listening to the interview encouraged them to get involved and speak up. However, we acknowledge a potential limitation that interviewing parental dyads may, in some cases, cause one or the other to have a more dominant voice. We intentionally sampled for a wide spread of factors to seek out certain perspectives (e.g., parent advocate and foster carer) and to ensure good sample diversity. Despite this, most, but not all, were white British (reflective of the wider cohort demographic spread), so not all of our findings can necessarily be generalised to all groups. Our cohort only includes children with GNDs. This means that our findings may not be generalisable to all rare diseases. Due to the nature of the study, some of our findings are likely to be relevant to wider patient groups such as those with chronic disease, other forms of disability and neurodiversity. The main interviewer is a senior clinical geneticist, who may represent an insider standpoint in these results. Reflective discussions with the second coder took place to recognise this, and we note that most parents felt empowered to discuss negative experiences with healthcare professionals, suggesting that her professional standing was not a barrier to expressing their views.