The perception, understanding and experience of flourishing in young people living with chronic pain: A Q-methodology study.

Much research has adopted a deficits-based approach to chronic pain, neglecting the study of flourishing. Using a Q-methodological framework, this study sought to explore how individuals experience, understand and perceive flourishing in the context of young people living with chronic pain. Fifty-four individuals completed a Q-sorting task, indicating their level of agreement and disagreement with 52 statements. Q-analysis generated three factors that represented clear viewpoints of participants: 'Pain is not a barrier to flourishing', 'Adapting to a new life' and 'Adopting a positive perspective'. Factors expressed the viewpoints that flexibility is key to enjoying life despite chronic pain, while resilience, management of stressors, acceptance and problem-solving may be required to flourish with chronic pain. Participants' understanding of flourishing also focused on the appreciation and enjoyment of life and achievements. This study provides a useful contribution towards furthering our understanding of flourishing in young people living with chronic pain.

Looking on the bright side: The relationships between flourishing and pain-related outcomes among adolescents living with chronic pain.

A deficits-based approach to adolescent chronic pain currently dominates the literature, to the exclusion of positive approaches, such as flourishing. Addressing this knowledge gap, this study examined the relationships between flourishing and pain-related outcomes in adolescent chronic pain. Seventy-nine adolescents aged 11-24 years were asked to complete self-report measures of three domains of flourishing and four pain-related outcomes. Correlation coefficients and four hierarchical linear regression analyses were conducted, controlling for age and gender. Flourishing mental health was associated with, and significantly contributed to explaining, anxiety and depressive symptoms, and social and family functioning impairment. Benefit finding and posttraumatic growth were each associated with social and family functioning impairment, while posttraumatic growth was also associated with anxiety and depressive symptoms. Additionally, benefit finding significantly contributed to explaining pain intensity. Study findings underscore the importance of assessing the relationships between flourishing and pain-related outcomes in adolescents with chronic pain.

Glass half full: A diary and interview qualitative investigation of flourishing among adolescents living with chronic pain.

BACKGROUND: Counter to paediatric pain literature that typically highlights the deleterious impacts associated with adolescent chronic pain, evidence suggests that some adolescents flourish in their experience of pain. This study sought to explore how adolescents experience, understand and perceive flourishing while living with chronic pain. METHODS: Twenty-four adolescents aged 11-24 years were recruited via clinical and online settings. All adolescents were asked to complete daily diary entries, with a subset of 10 participants asked to complete follow-up interviews. RESULTS: Inductive reflexive thematic analysis generated two themes: 'Appreciating the moment' and 'Becoming a better version of myself'. Themes addressed how self and other comparisons facilitated a renewed appreciation for achievements and pleasures in life due to living with chronic pain. Adolescents further demonstrated a perception of continued personal and social growth in their experience of chronic pain, including increased emotional maturity, resilience, positivity, kindness and improved communication skills. CONCLUSIONS: We conclude that adolescents can experience positive changes in functioning and flourish in some domains of life despite, or resulting from, chronic pain. Further research with an exclusive focus on flourishing is needed to build on this work and address this important gap in knowledge. SIGNIFICANCE: We present evidence that adolescents can flourish when living with chronic pain. Such knowledge may inform the development of positive psychological treatment strategies that are focused on reinforcing adolescents' existing strengths, to expand on current treatment options for adolescents living with chronic pain.

The role of perceived organisational justice in the experience of pain among male and female employees.

This study examined the association of organisational justice with pain among employees of a large organisation. Employees (n = 1829) completed measures of pain, fair pay, organisational justice, job satisfaction and stress. Logistic regression analyses found that organisational justice was unrelated to pain among women, but men with higher perceptions of fair pay were more likely to report chronic pain as were men with lower perceptions of distributive justice. This is the first study indicating that fair pay and distributive justice are both unique predictors of chronic pain in men. The findings have implications for supporting employees with chronic pain.

Parenting an adolescent with complex regional pain syndrome: A dyadic qualitative investigation of resilience.

OBJECTIVES: Adolescent chronic pain exists within a social context, affecting the lives of adolescents, parents, peers, and wider family members. Typically, parental research has focussed on the negative impact on parents associated with parenting an adolescent with chronic pain. However, a small number of studies have identified positive parental outcomes and functioning, with a focus on parental resilience. This study sought to extend existing knowledge by providing a detailed and contextualized understanding of how parental dyads experience and demonstrate resilience in response to parenting an adolescent with Complex Regional Pain Syndrome (CRPS) and the meaning that parents ascribe to these shared experiences. DESIGN: An Interpretative Phenomenological Analysis (IPA) was used to conduct an in-depth qualitative interview study of parents of an adolescent with CRPS. METHODS: Semi-structured interviews were conducted via Skype with eight mother-father parental dyads of an adolescent aged 11-25 years with CRPS. RESULTS: A single prominent theme 'masking reality in the face of pain' dominated the parental discourse and experience of resilience. Resilience was experienced as an incongruence between private distress and the perceived obligation to display socially desirable resilience behaviours to protect their child from their own distress. CONCLUSIONS: Study findings highlight the benefits of strength-based interventions to enhance parental resilience. This is particularly important since parental behaviours have been shown to influence child pain outcomes. Future research should seek to explore resilience in different populations such as lone parents, siblings, and those parenting an adolescent with pain conditions other than CRPS.

Flourishing among adolescents living with chronic pain and their parents: A scoping review.

Evidence exists regarding the impact of flourishing in individuals living with chronic pain, but there are currently no reviews which collate the literature on flourishing in adolescents living with chronic pain and their parents. Therefore, the aim of this scoping review was to map and review the current literature, to document how flourishing is defined and understood in the literature, and to identify gaps in the field. Six databases were searched (Web of Science, Medline, Embase, APA PsycNet and the Cochrane Central Register of Controlled Trials). In addition, a limited gray literature search was conducted. The resulting data were collated and reported in relation to the review questions, by examining the included papers to search for the presence of flourishing. Database searches resulted in 7326 papers after duplicate removal, with eight remaining papers being assessed for full-text eligibility. Following full-text screening, a final four papers were included in the review. Within the papers, flourishing was defined in relation to commonalities of benefit finding, enhanced maturity and growth, and social support. Gaps in the literature and directions for future research are considered. This review suggests that there is a dearth of knowledge and research regarding flourishing among adolescents living with chronic pain and their parents, despite aspects of flourishing identified in limited literature. This warrants further investigation.

A scoping review to ascertain the parameters for an evidence synthesis of psychological interventions to improve work and wellbeing outcomes among employees with chronic pain.

BACKGROUND: Psychological interventions have mixed effects on improving employee outcomes, partly due to significant variability across studies and a lack of focus on mechanisms of action. This scoping review reports on the parameters of these interventions and examines intervention content to bring clarity to this heterogeneous topic area and direct future systematic review work. METHOD: Six databases were searched (Cinahl, Cochrane, Embase, Medline, PsychINFO and Web of Science) from April 2010 to August 2020, and a grey literature search was undertaken. Screening was undertaken independently by two authors. The results summarised country, participant and employment characteristics, psychological interventions and work, health and wellbeing outcomes. 10% of the papers were analysed to determine the feasibility of coding intervention descriptions for theory and behaviour change technique (BCT) components. RESULTS: Database searches yielded 9341 titles, of which 91 studies were included. Most studies were conducted in Europe (78%) and included males and females (95%) ranging in age from 31-56.6 years although other demographic, and employment information was lacking. Musculoskeletal pain was common (87%). Psychological interventions commonly included cognitive behavioural therapy (30%) and education (28%). Most studies employed a randomised control trial design (64%). Over half contained a control group (54%). Interventions were delivered in mostly healthcare settings (72%) by health professionals. Multiple outcomes were often reported, many of which involved measuring sickness absence and return-to-work (62%) and pain and general health (53%). Within the feasibility analysis, most papers met the minimum criteria of containing one paragraph of intervention description, but none explicitly mentioned theory or BCTs. CONCLUSION: Psychological interventions for employees with chronic pain vary in their nature and implementation. We have shown scoping reviews can be used to assess the feasibility of applying tools from health psychology to identify the content of these interventions in future systematic review work to improve intervention development.

Effects of Regular Physical Activity on the Immune System, Vaccination and Risk of Community-Acquired Infectious Disease in the General Population: Systematic Review and Meta-Analysis.

BACKGROUND: Regular physical activity is the prime modality for the prevention of numerous non-communicable diseases and has also been advocated for resilience against COVID-19 and other infectious diseases. However, there is currently no systematic and quantitative evidence synthesis of the association between physical activity and the strength of the immune system. OBJECTIVE: To examine the association between habitual physical activity and (1) the risk of community-acquired infectious disease, (2) laboratory-assessed immune parameters, and (3) immune response to vaccination. METHODS: We conducted a systemic review and meta-analysis according to PRISMA guidelines. We searched seven databases (MEDLINE, Embase, Cochrane CENTRAL, Web of Science, CINAHL, PsycINFO, and SportDiscus) up to April 2020 for randomised controlled trials and prospective observational studies were included if they compared groups of adults with different levels of physical activity and reported immune system cell count, the concentration of antibody, risk of clinically diagnosed infections, risk of hospitalisation and mortality due to infectious disease. Studies involving elite athletes were excluded. The quality of the selected studies was critically examined following the Cochrane guidelines using ROB2 and ROBINS_E. Data were pooled using an inverse variance random-effects model. RESULTS: Higher level of habitual physical activity is associated with a 31% risk reduction (hazard ratio 0.69, 95% CI 0.61-0.78, 6 studies, N = 557,487 individuals) of community-acquired infectious disease and 37% risk reduction (hazard ratio 0.64, 95% CI 0.59-0.70, 4 studies, N = 422,813 individuals) of infectious disease mortality. Physical activity interventions resulted in increased CD4 cell counts (32 cells/µL, 95% CI 7-56 cells/µL, 24 studies, N = 1112 individuals) and salivary immunoglobulin IgA concentration (standardised mean difference 0.756, 95% CI 0.146-1.365, 7 studies, N = 435 individuals) and decreased neutrophil counts (704 cells/µL, 95% CI 68-1340, 6 studies, N = 704 individuals) compared to controls. Antibody concentration after vaccination is higher with an adjunct physical activity programme (standardised mean difference 0.142, 95% CI 0.021-0.262, 6 studies, N = 497 individuals). CONCLUSION: Regular, moderate to vigorous physical activity is associated with reduced risk of community-acquired infectious diseases and infectious disease mortality, enhances the first line of defence of the immune system, and increases the potency of vaccination. PROTOCOL REGISTRATION: The original protocol was prospectively registered with PROSPERO (CRD42020178825).

Child pain-related injustice appraisals mediate the relationship between just-world beliefs and pain-related functioning.

BACKGROUND: Research among adult and paediatric samples suggests that pain-related injustice appraisals contribute to adverse pain-related functioning. However, a singular focus on pain-related injustice appraisals carries the risk of underestimating the role of broader concepts of justice. This study examined the unique roles of child pain-related injustice appraisals and just-world beliefs in understanding disability and physical, emotional, social and academic functioning, as well as the mediating role of injustice appraisals in the relationship between just-world beliefs and functioning. METHODS: Participants comprised a school sample of 2,174 children (Study 1) and a clinical sample of 146 paediatric chronic pain patients (Study 2) who completed the Injustice Experience Questionnaire (IEQ), Personal and General Belief in a Just World scales (JWB-P/G), Functional Disability Inventory (FDI), Pain Catastrophizing Scale for Children (PCS-C) and Pediatric Quality of Life Inventory (PEDSQL). RESULTS: For both samples, child pain-related injustice appraisals were associated with poorer functioning, after controlling for just-world beliefs, catastrophizing, pain intensity, age and sex. In the school sample, injustice appraisals mediated the associations of both personal and general just-world beliefs with functioning. In the clinical sample, injustice appraisals mediated the association of personal, but not general, just-world beliefs with all functioning scales. CONCLUSIONS: The current findings attest to the unique role of pain-related injustice appraisals in understanding child pain-related functioning and their explanatory value in understanding the relationship between fundamental just-world beliefs and child pain-related functioning. SIGNIFICANCE: The present study adds to emerging literature on the adverse effects of child pain-related injustice appraisals in the context of pain, through showing that pain-related injustice appraisals are uniquely associated with pain-related functioning and mediate the relationship between just-world beliefs and pain-related functioning. These findings suggest that interventions may target pain-related injustice appraisals as a mechanism for change in children.

Mothers' appraisals of injustice in the context of their child's chronic pain: An interpretative phenomenological analysis.

BACKGROUND: In line with research highlighting the role of observer appraisals in understanding individuals' pain experience, recent work has demonstrated the effects of parental child- and self-oriented injustice appraisals on child pain-related outcomes. However, research on parental injustice appraisals is in its infancy and lacks a valid and context-specific operationalization of what parental injustice appraisals of child pain precisely entail. The current study presents an in-depth qualitative analysis of parental child- and self-oriented appraisals of injustice in the context of their child's chronic pain. METHODS: Twenty-one mothers of children living with chronic pain participated in one of five focus group interviews conducted in Ghent (Belgium), Glasgow (Scotland) and Indianapolis (USA). RESULTS: The interviews were subjected to interpretative phenomenological analysis, which revealed three key justice-related themes, labelled 'You shouldn't be in this much pain', 'The problem's probably with the mother' and 'At least it's not cancer'. Maternal injustice appraisals focused mainly on the child rather than the self and reflected various perceived barriers to their efforts to provide quality of life for their child. A fourth theme labelled 'Not everybody gets a healthy child' reflected maternal strategies to effectively cope with the child's condition and the associated appraisals of injustice. CONCLUSIONS: The current findings attest to the relevance of (child- and self-oriented) injustice in the parental experience of caring for a child with chronic pain and provides insight into the specific content and scope of these appraisals. As such, this study provides valuable insights to further research in this area. SIGNIFICANCE: The current study presents an in-depth qualitative analysis of parental appraisals of injustice in the context of their child's chronic pain condition. The findings provide valuable insights into the phenomenology of this construct and may inform future research and assessment methods. Furthermore, the themes reported in this study may contribute to clinical practice, as they may raise awareness of parental concerns regarding their child's pain management.

Parental Injustice Appraisals in the Context of Child Pain: Examining the Construct and Criterion Validity of the IEQ-Pc and IEQ-Ps.

A growing pediatric and adult literature highlights the role of injustice appraisals in adjustment to pain. However, interpersonal injustice dynamics have remained largely unexplored. The present study investigated the factor structure and criterion validity of parentally adjusted versions of the Injustice Experience Questionnaire, assessing child-oriented (IEQ-Pc) and self-oriented appraisals (IEQ-Ps) in the context of child pain. Participants were triads of healthy children (N = 407, Mage = 12) and both their parents and dyads of children with chronic pain (N = 319, Mage = 14) and 1 parent. In both samples, children completed measures of functional disability and quality of life (physical, emotional, social, and academic); parents completed the IEQ-Pc, IEQ-Ps, and a measure of parental catastrophizing about child pain. Across samples, a confirmatory oblique two-factor model (Severity/Irreparability-Blame/Unfairness) provided a better fit to the data compared to a one-factor model; nevertheless, the two-factor solution was considered suboptimal. A post hoc exploratory factor analysis consistently revealed 1 factor. In terms of criterion validity, the IEQ-Pc and IEQ-Ps demonstrated differential associations depending on the child's pain versus healthy status, independent of parental catastrophizing. Further, findings in the healthy sample indicated that fathers' self-oriented injustice appraisals related to lower child social function. In the clinical sample, parental child-oriented injustice appraisals related to greater child functional disability and lower physical, emotional, social, and academic function. Current findings support the unique role of parental injustice appraisals, assessed by the IEQ-Pc and IEQ-Ps, in understanding child pain, but also suggest these may only partially capture the phenomenology of parental injustice appraisals in the context of child pain. PERSPECTIVE: This manuscript presents an examination of the construct and criterion validity of 2 parentally adjusted versions of the Injustice Experience Questionnaire. These measures could be valuable tools for clinicians in examining how parents respond to their child's pain as it impacts both the child's life and the parents'.

A visual affective analysis of mass media interventions to increase antimicrobial stewardship amongst the public.

OBJECTIVES: In an innovative approach to improve the contribution of health psychology to public health we have analysed the presence and nature of affect within the visual materials deployed in antimicrobial stewardship interventions targeting the public identified through systematic review. DESIGN: A qualitative analysis focused on the affective content of visual materials garnered from a systematic review of antibiotic stewardship (k = 20). METHODS: A novel method was devised drawing on concepts from semiotics to analyse the affective elements within intervention materials. RESULTS: Whilst all studies examined tacitly rely on affect, only one sought to explicitly deploy affect. Three thematic categories of affect are identified within the materials in which specific ideological machinery is deployed: (1) monsters, bugs, and superheroes; (2) responsibility, threat, and the misuse/abuse of antibiotics; (3) the figure of the child. CONCLUSIONS: The study demonstrates how affect is a present but tacit communication strategy of antimicrobial stewardship interventions but has not - to date - been adequately theorized or explicitly considered in the intervention design process. Certain affective features were explored in relation to the effectiveness of antimicrobial resistance interventions and warrant further investigation. We argue that further research is needed to systematically illuminate and capitalize upon the use of affect to effect behaviour change concerning antimicrobial stewardship. Statement of contribution What is already known on this subject? The (mis)use of antibiotics and consequent risk of antimicrobial resistance is a critical public health problem. If sufficient action is not taken, global society will face the 'post-antibiotic' era, in which common infections will lead to death for many millions. Key desirable behavioural changes are decreased patient demands for antibiotics, use of them for targeted purposes alone, and compliance with prescribed dosing. There is a growth of interest in the role of affect in mass media interventions designed to engage publics and produce health-related behavioural change. What does this study add? This article presents a novel analytic approach to understanding and intervening within behaviour change in public health that may complement other types of analysis. We present findings specifically from an 'affective' analysis based on semiotics in which we critically interrogated the visual imagery being deployed in mass media public health interventions concerning antimicrobial stewardship. Three thematic categories of affect are identified within the materials in which specific ideological machinery is deployed and that demonstrate some association with intervention effectiveness worthy of further investigation and testing.

What are the 'active ingredients' of interventions targeting the public's engagement with antimicrobial resistance and how might they work?

OBJECTIVES: Changing public awareness of antimicrobial resistance (AMR) represents a global public health priority. A systematic review of interventions that targeted public AMR awareness and associated behaviour was previously conducted. Here, we focus on identifying the active content of these interventions and explore potential mechanisms of action. METHODS: The project took a novel approach to intervention mapping utilizing the following steps: (1) an exploration of explicit and tacit theory and theoretical constructs within the interventions using the Theoretical Domains Framework (TDFv2), (2) retrospective coding of behaviour change techniques (BCTs) using the BCT Taxonomy v1, and (3) an investigation of coherent links between the TDF domains and BCTs across the interventions. RESULTS: Of 20 studies included, only four reported an explicit theoretical basis to their intervention. However, TDF analysis revealed that nine of the 14 TDF domains were utilized, most commonly 'Knowledge' and 'Environmental context and resources'. The BCT analysis showed that all interventions contained at least one BCT, and 14 of 93 (15%) BCTs were coded, most commonly 'Information about health consequences', 'Credible source', and 'Instruction on how to perform the behaviour'. CONCLUSIONS: We identified nine relevant TDF domains and 14 BCTs used in these interventions. Only 15% of BCTs have been applied in AMR interventions thus providing a clear opportunity for the development of novel interventions in this context. This methodological approach provides a useful way of retrospectively mapping theoretical constructs and BCTs when reviewing studies that provide limited information on theory and intervention content. Statement of contribution What is already known on this subject? Evidence of the effectiveness of interventions that target the public to engage them with AMR is mixed; the public continue to show poor knowledge and misperceptions of AMR. Little is known about the common, active ingredients of AMR interventions targeting the public and information on explicit theoretical content is sparse. Information on the components of AMR public health interventions is urgently needed to enable the design of effective interventions to engage the public with AMR stewardship behaviour. What does this study add? The analysis shows very few studies reported any explicit theoretical basis to the interventions they described. Many interventions share common components, including core mechanisms of action and behaviour change techniques. The analysis suggests components of future interventions to engage the public with AMR.

Effectiveness of interventions to improve the public's antimicrobial resistance awareness and behaviours associated with prudent use of antimicrobials: a systematic review.

Background: A global antimicrobial resistance (AMR) awareness intervention targeting the general public has been prioritized. Objectives: To evaluate the effectiveness of interventions that aim to change AMR awareness and subsequent stewardship behaviours amongst the public. Methods: Five databases were searched between 2000 and 2016 for interventions to change the public's AMR awareness and/or antimicrobial stewardship behaviours. Study designs meeting the Cochrane Effective Practice and Organization of Care (EPOC) criteria, non-controlled before-and-after studies and prospective cohort studies were considered eligible. Participants recruited from healthcare settings and studies measuring stewardship behaviours of healthcare professionals were excluded. Quality of studies was assessed using EPOC risk of bias criteria. Data were extracted and synthesized narratively. Registration: PROSPERO international prospective register of systematic reviews (PROSPERO 2016: CRD42016050343). Results: Twenty studies were included in the review with nine meeting the EPOC criteria. The overall risk of bias was high. Nineteen studies were conducted in high-income countries. Mass media interventions were most common (n = 7), followed by school-based (n = 6) and printed material interventions (n = 6). Seventeen studies demonstrated a significant effect on changing knowledge, attitudes or the public's antimicrobial stewardship behaviours. Analysis showed that interventions targeting schoolchildren and parents have notable potential, but for the general public the picture is less clear. Conclusions: Our work provides an in-depth examination of the effectiveness of AMR interventions for the public. However, the studies were heterogeneous and the quality of evidence was poor. Well-designed, experimental studies on behavioural outcomes of such interventions are required.

Catastrophizing Mediates the Relationship Between the Personal Belief in a Just World and Pain Outcomes Among Chronic Pain Support Group Attendees.

Health-related research suggests the belief in a just world can act as a personal resource that protects against the adverse effects of pain and illness. However, currently, little is known about how this belief, particularly in relation to one's own life, might influence pain. Consistent with the suggestions of previous research, the present study undertook a secondary data analysis to investigate pain catastrophizing as a mediator of the relationship between the personal just world belief and chronic pain outcomes in a sample of chronic pain support group attendees. Partially supporting the hypotheses, catastrophizing was negatively correlated with the personal just world belief and mediated the relationship between this belief and pain and disability, but not distress. Suggestions for future research and intervention development are made.

Refinement of genotype-phenotype correlation in 18 patients carrying a 1q24q25 deletion.

Interstitial deletion 1q24q25 is a rare rearrangement associated with intellectual disability, growth retardation, abnormal extremities and facial dysmorphism. In this study, we describe the largest series reported to date, including 18 patients (4M/14F) aged from 2 days to 67 years and comprising two familial cases. The patients presented with a characteristic phenotype including mild to moderate intellectual disability (100%), intrauterine (92%) and postnatal (94%) growth retardation, microcephaly (77%), short hands and feet (83%), brachydactyly (70%), fifth finger clinodactyly (78%) and facial dysmorphism with a bulbous nose (72%), abnormal ears (67%) and micrognathia (56%). Other findings were abnormal palate (50%), single transverse palmar crease (53%), renal (38%), cardiac (38%), and genital (23%) malformations. The deletions were characterized by chromosome microarray. They were of different sizes (490 kb to 20.95 Mb) localized within chromosome bands 1q23.3-q31.2 (chr1:160797550-192912120, hg19). The 490 kb deletion is the smallest deletion reported to date associated with this phenotype. We delineated three regions that may contribute to the phenotype: a proximal one (chr1:164,501,003-167,022,133), associated with cardiac and renal anomalies, a distal one (chr1:178,514,910-181,269,712) and an intermediate 490 kb region (chr1:171970575-172460683, hg19), deleted in the most of the patients, and containing DNM3, MIR3120 and MIR214 that may play an important role in the phenotype. However, this genetic region seems complex with multiple regions giving rise to the same phenotype.

Gross deletions in TCOF1 are a cause of Treacher-Collins-Franceschetti syndrome.

Treacher-Collins-Franceschetti syndrome (TCS) is an autosomal dominant craniofacial disorder characterised by midface hypoplasia, micrognathia, downslanting palpebral fissures, eyelid colobomata, and ear deformities that often lead to conductive deafness. A total of 182 patients with signs consistent with a diagnosis of TCS were screened by DNA sequence and dosage analysis of the TCOF1 gene. In all, 92 cases were found to have a pathogenic mutation by sequencing and 5 to have a partial gene deletion. A further case had a novel in-frame deletion in the alternatively spliced exon 6A of uncertain pathogenicity. The majority of the pathogenic sequence changes were found to predict premature protein termination, however, four novel missense changes in the LIS1 homology motif at the 5' end of the gene were identified. The partial gene deletions of different sizes represent ~5.2% of all the pathogenic TCOF1 mutations identified, indicating that gene rearrangements account for a significant proportion of TCS cases. This is the first report of gene rearrangements resulting in TCS. These findings expand the TCOF1 mutation spectrum indicating that dosage analysis should be performed together with sequence analysis, a strategy that is predicted to have a sensitivity of 71% for patients in whom TCS is strongly suspected.