Experiences of adolescents living with Silver-Russell syndrome

Objective The psychosocial impact of growing up with Silver-Russell syndrome (SRS), characterised by growth failure and short stature in adulthood, has been explored in adults; however, there are no accounts of contemporary lived experience in adolescents. Such data could inform current healthcare guidance and transition to adult services. We aimed to explore the lived experience of adolescents with SRS. Design/setting/patients In-depth, semi-structured interviews were conducted between January 2015 and October 2016 with a sample of eight adolescents aged 13–18 (five girls) with genetically confirmed SRS from the UK. Qualitative interviews were transcribed and coded to identify similarities and differences using thematic analysis; codes were then grouped to form overarching themes. Results We identified four themes from the interview data: (1) the psychosocial challenges of feeling and looking different; (2) pain, disability and fatigue; (3) anticipated stigma; and (4) building resilience and acceptance. Despite adolescents accepting SRS in their lives, they described ongoing psychosocial challenges and anticipated greater problems to come, such as stigma from prospective employers. Conclusions Adolescents with SRS may experience psychosocial difficulties from as young as 10 years old related to feeling and looking different; pain, disability and fatigue; anticipated stigma; and future challenges around employment. We discuss these findings in relation to recommendations for the care of adolescents with SRS to prepare them for adult life. In depth qualitative interviews with young people growing up with Silver- Russell syndrome identified multiple psychosocial challenges. Currently young people are discharged and not monitored into adulthood. This may need to change


INTRODUCTION
Silver-Russell syndrome (SRS) is a rare genetic condition characterised by slow growth in utero leading to poor postnatal growth, short stature in adulthood, triangular facial appearance, asymmetry, feeding difficulties, 1 low muscle mass and poor muscle function. 2 A recent study estimated SRS incidence as 1:15 866 3 -higher than previous estimates 4 -with males and females equally affected. 1 Two molecular abnormalities cause the majority (60%) of SRS cases, 5 but a significant minority of patients have no known molecular cause. 1 Management of SRS during childhood focuses on optimising final height through nutrition and growth hormone (GH) therapy.
Our recent qualitative research showed that adults living with SRS dealt with psychosocial challenges through childhood and adolescence; they had appearance-related concerns beyond their height and experienced difficulties in forming romantic relationships. 6 Women reported experiencing pain and disability, impacting on employment and familial relationships. As part of our broader programme of research, 6 7 we interviewed adolescents (aged 13-18 years) to explore their lived experience of SRS.
There is a level of uncertainty regarding issues and challenges requiring the focus and attention of health professionals working with people living with SRS, due to a dearth of published literature reporting on the lived experience of children and adolescents with short stature conditions, such as SRS. One qualitative study of 29 young women with Turner's syndrome showed that participants were troubled by teasing in school about being small, which for some persisted into adulthood, and about infertility resulting in a fear of initiating romantic relationships and remaining single. 8 Survey studies found that adolescents living with Turner's syndrome report problems with social functioning 9 ; reduced health-related quality of life What is already known on this topic? ► The clinical management of Silver-Russell syndrome (SRS) during childhood has a major focus on optimising height. ► Psychosocial evaluation is not routinely offered to children and adolescents in clinics. ► Appearance-related concerns result in psychological distress for some individuals living with SRS.

What this study adds?
► Aspects of the lived experience, such as pain, disability, feeling different, anticipated stigma and resilience, are similar in adolescents and adults living with SRS. ► Pain can be a symptom for girls with SRS, which is currently undocumented in existing literature. The causes and management of pain requires further investigation. ► Health professionals need to offer psychosocial support to adolescents as they prepare to discharge them to adult services.

Original research
(QoL) 10 ; and prior GH treatment had no impact on QoL in adulthood. 11 We set out to explore and evaluate the lived experiences of adolescents living with SRS to inform clinical management up to adolescence and beyond. Qualitative methods for data collection and analysis allowed for rich data to be generated and examined to gain in-depth understanding of these experiences. [12][13][14]

METHOD Public and patient involvement
A member of the Child Growth Foundation-a UK charity that supports people affected by child growth conditions-who had personal experience of a growth condition, was also part of the research team. This charity member was involved in the development of the funding application, attended project steering group meetings, helped develop patient information leaflets and consent forms, advised on recruitment and analysis and was involved in the dissemination of project findings.

Identification of adolescents with SRS
Participants were recruited from a larger study investigating the health consequences of SRS in young people 7 and from a patient support group. Research and development approval was secured from University Hospital Southampton National Health Service Foundation Trust (study sponsor) and, for the 23 UK Genetics Centres, via the National Institute for Health Research UK Rare Genetic Disease Research Consortium Agreement ('Musketeers' memorandum'). Individuals were identified across the UK through: (1) study information disseminated by the Child Growth Foundation, UK; (2) prior recruitment to an existing national study 'Imprinting Disorders: finding out why' with expressed interest in further research; (3) review of positive molecular genetics tests at the Wessex Regional Genetics Laboratory; and (4) contact with regional genetic and paediatric endocrine centres at existing genetics research sites.
Using the first two approaches, participants were sent information by post and invited to contact the study team or were contacted by telephone if they had previously given permission. For the other two approaches, the patient's overseeing clinician

Figure 2
Source of recruitment to qualitative study. *Recruitment of 374 participants was from a larger study. Recruitment to the current study focused on those aged 18-years years or younger.
was contacted and asked to post study information to their patient.

Study interviews
Interviews were chosen as they allowed the researcher to focus on drawing out individual experiences; explore specific concerns or issues; be flexible when wording questions and add questions about relevant topics that arose. 14 As SRS is a rare condition and individuals may be known through support groups, robust confidentiality measures were instituted, including numerical participant identification and the use of age ranges. The interview schedule addressed the impact of SRS on key aspects of a participant's life (education, work, friends, family and intimate relationships). This was piloted with people living with a chronic health condition, before commencing recruitment to our adult lived experience study. 6 Piloting the schedule allowed us to assess how appropriate the questions were, if they were in an order that made sense and to practice asking the questions. We made several adjustments based on interviewee feedback, for example, taking out questions that were difficult to answer, were repeative or needed reordering. Each interview took 30-60 mins and was audio recorded. Interviews were conducted by a trained female health psychologist (LMB) experienced in discussing sensitive health issues with patients. We gauged parents' thoughts about the interview and, although this may have placed parents in a 'gatekeeper' position, none declined an interview on their child's behalf. Parents and adolescents had the option of having a parent/ trusted person present for the interview, and two participants were interviewed with parents present (see figure 1 for more considerations). All participants were provided with an information sheet and the opportunity to discuss the research and ask questions. Written consent/assent was gained from adolescents and their parents. Participants were reassured that they could discontinue the interview at any time and that it would be audio recorded, but this could be stopped at their request.

Analysis of study interviews
Interviews were transcribed and analysed thematically using the Braun and Clarke method. 12 Codes were generated from the first few interviews and then refined as subsequent interviews were analysed. Codes were then grouped to create categories and developed into four overarching themes. To ensure rigour in developing themes, coding and categories were independently reviewed by three researchers (LMB, AF and EJ). Tracy's 15 criteria were used to enhance the validity and overall quality of the study. Qualitative data were managed with NVivo software (QSR International, V.11.3.2 (1888) for Mac). To triangulate our findings, we presented them to adolescents living with SRS and their families. Feedback from this reassured us that our conceptual work reflected participant's lived experiences.

Study participants
Eight participants (five girls) aged 13-18 years were interviewed (see figure 2 and table 1 for details). Six participants were recruited from a broader study (of nine adolescents, six agreed to participate and three were uncontactable) and two from a patient support group. The number of participants declined is not known as adolescents were asked to approach the researcher if they were interested in taking part. Three participants had a loss of methylation at 11p15, four had maternal uniparental disomy of chromosome 7; one was genetically confirmed with the specific diagnosis not revealed to the researcher; six had received GH treatment, one had not and for one this was unknown.  For some, the inability to participate fully in physical education was no great loss: 'They're all able to like throw things, all the things and I can't. But that doesn't really bother me because I'm not really into sports in the first place' (P03_F), but we speculate it is possible that not being able to take part in sports from an early age may have led to a dislike for this subject. Others, who would have liked to be more involved in sport, were fearful of exclusion due to perceived lack of ability.

Anticipated stigma: 'I hope it doesn't affect getting a job'
Some participants anticipated future stigmatisation or discrimination because of having SRS ( Building resilience and acceptance: 'You're not always going to be perfect' Of the strategies for responding to adversity identified in the data (table 5), many could be classed as coping or adaptive strategies, such as capitalising on social support. Participants appreciated opportunities to be with people like them, for example, at school with a person who is also hard of hearing, or at a convention with others who have SRS. While some participants described downward social comparison with others-for example, P02_F feeling 'quite well off' compared with other girls with SRSothers described a form of 'upward comparison', comparing themselves with people they believed to be more fortunate than themselves.   I've got everything'. Nonetheless, these participants seemed to have found some acceptance by understanding that no one is 'perfect': 'I've learnt that you're not always going to be perfect, there's always going to be something'. P01_F described anxiety and confidence issues while in mainstream secondary school, but after starting special education, where she felt she was 'one of the more able students', she stated her confidence improved. Most participants described the significant role of their family in supporting them through treatment, medical appointments and other challenges and also reported valuing the support of friends.

DISCUSSION
To our knowledge, this is the first study exploring contemporary experiences of adolescents living with SRS. While resilience was described, most participants described psychosocial challenges and anticipated more to come. For example, stigma owing to their height, having a genetic condition and feeling different from their peers. Most of the girls in the sample reported experiencing pain and discussed how physical disability played a part in their lives. Participants described feeling different from peers, and being treated differently, often as early as age 10 years. Some reported experiencing bullying associated with SRS when younger, for example, appearance, hearing problems and having a stammer. These findings parallel those of our adult study 6 and reinforce the conclusion that childhood and adolescent challenges are likely to have a significant psychosocial impact on adults living with SRS. 6 Previous research on patients with Turner's syndrome suggested that QoL outcomes could be improved by addressing concerns about height by age 6-12 years at the latest. 16 17 Our studies suggest likewise; psychosocial evaluation and support by around age 10 years would assist during adolescence and in the transition to secondary school.
Participants reported coping with feeling different by comparing themselves with others less fortunate than themselves, capitalising on social support from friends and family and accessing support groups. These skills, which foster resilience, are important to positive adjustment when feeling or looking different. 18 Accessing support groups can be particularly beneficial; and some participants were members of online support groups. Participants may have gained social capital by forming friendships 19 . Downward comparison can be made with those in a similar situation, increasing self-esteem 20 and upward comparison can increase feelings of hope and motivation; 21 simply being with others who are similar may give people some respite from feeling different. 20 Accessing the support offered by friends and family can also reduce stress 22 and help cope with the challenges that living with a chronic condition can raise. 23 Most girls in the study reported pain and disability, largely absent in accounts from boys; fatigue was discussed by a minority of all participants. This novel finding is of interest and complements our previous data in adults with SRS where we found that adult women's experience of SRS was one of pain, fatigue and disability, a phenomenon little documented in existing literature. 6 Although approximately a third of adolescents in Europe experience fatigue, [24][25][26] it may be more significant in individuals with SRS because of their tendency to low lean mass. 6 Our findings require verification in other cohorts and further study regarding the causative mechanisms of pain and disability among girls/women living with SRS.
Participants reported being treated differently due to their appearance and wanting to change the way they looked in order to fit in. These findings again echo those from our adult  Figure 3 Recommendations by theme. SRS, Silver-Russell syndrome.

Original research
study, where adults reported difficulties in adolescence forming romantic relationships that, for some, persisted into adulthood. 6 However, adolescent participants did not report present or anticipated issues with dating, perhaps some were too young or participants may have hesitated to discuss such sensitive topics with the interviewer, as suggested by one young person who declined to comment on the topic. Previous research has found that having a visible difference does not appear to prevent adolescents from embarking on romantic relationships, but many experienced concern about future relationships or current relationships progressing. 27 Future research should include the exploration of romantic relationships in relation to visible differences for people living with SRS. Currently, clinical management of SRS focuses on height optimisation, but our data show that appearance-related concerns and psychosocial issues require at least equal attention. This study demonstrates enduring issues for people living with SRS and gives rise to specific recommendations for professionals working with this group (figure 3). Support for children and adolescents should include: increased understanding of psychosocial issues among clinicians, teachers and family members; access to psychological support for appearance-related concerns and management of pain and fatigue 28 ; peer support 29 ; career advice sensitive to concerns regarding living with a health condition; and guidance on diet and exercise, especially after GH treatment stops, 30 as people with SRS may be at risk of metabolic problems in adulthood. 7 When implementing these recommendations, it is important to highlight that severity of condition 31 32 or visible difference 33 is not related to psychological distress.

Strengths, limitations and future directions
Our study had several limitations. First, our sample was small and lacked diversity (eg, gender, ethnicity and culture) though this was unavoidable due to the rarity of SRS and difficulties in recruitment of adolescents. 34 However, as our adolescent data and adult reports of adolescence are similar (ie, pain, disability, feeling different, anticipated stigma and resilience), the current study adds weight to our adult findings. Moreover, as it explored a specific, rare and previously undescribed experience, a smaller number of participants was acceptable due to higher information power. 35 Second, we suspect our findings regarding more sensitive topics, such as dating and mental health issues, may not represent the full picture for adolescents living with SRS.

CONCLUSION
Adolescents with SRS may experience psychosocial difficulties related to feeling and looking different; pain, disability and fatigue; anticipated stigma; and future challenges around employment. Unlike conditions such as Turner's syndrome that have medical issues monitored into adulthood, adolescents living with SRS are discharged from healthcare at a pivotal time when they require the most psychosocial support. Clinicians involved in the care of adolescents with SRS should be aware of the experiences highlighted here to support their patients now and prepare them for the future when discharged from the specialist service. Without such guidance, people living with SRS risk biopsychosocial problems that could be ameliorated with appropriate prevention and/or treatment interventions.