Epidemiology, aetiology, interventions and genomics in children with arthrogryposis multiplex congenita: protocol for a multisite registry.

INTRODUCTION: Arthrogryposis multiplex congenita (AMC) is an umbrella term including hundreds of conditions with the common clinical manifestation of multiple congenital contractures. AMC affects 1 in 3000 live births and is caused by lack of movement in utero. To understand the long-term needs of individuals diagnosed with a rare condition, it is essential to know the prevalence, aetiology and functional outcomes in a large sample. The development and implementation of a multicentre registry is critical to gather this data. This registry aims to improve health through genetic and outcomes research, and ultimately identify new therapeutic targets and diagnostics for treating children with AMC. METHODS AND ANALYSIS: Participants for the AMC registry will be recruited from seven orthopaedic hospitals in North America. Enrollment occurs in two phases; Part 1 focuses on epidemiology, aetiology and interventions. For this part, retrospective and cross-sectional data will be collected using a combination of patient-reported outcomes and clinical measures. Part 2 focuses on core subset of the study team, including a geneticist and bioinformatician, identifying causative genes and linking the phenotype to genotype via whole genome sequencing to identify genetic variants and correlating these findings with pedigree, photographs and clinical information. Descriptive analyses on the sample of 400 participants and logistic regression models to evaluate relationships between outcomes will be conducted. ETHICS AND DISSEMINATION: Ethical approval has been granted from corresponding governing bodies in North America. Dissemination of findings will occur via traditional platforms (conferences, manuscripts) for the scientific community. Other modalities will be employed to ensure that all stakeholders, including youth, families and patient support groups, may be provided with findings derived from the registry. Ensuring the findings are circulated to a maximum amount of interested parties will ensure that the registry can continue to serve as a platform for hypothesis-driven research and further advancement for AMC.

Rehabilitation needs of youth with arthrogryposis multiplex congenita: Perspectives from key stakeholders.

Background: Arthrogryposis multiplex congenita is a term used to describe congenital contractures in at least two body parts with an overall prevalence of 1 in 3000 live births. It is often caused by lack of fetal movement in utero and presents as contractures of varying severity, which may affect the upper and lower extremities, the spine and jaw. Currently, no practice recommendations exist to inform best clinical practice for arthrogryposis multiplex congenita.Purpose: To identify the needs surrounding rehabilitation as experienced by youth with arthrogryposis multiplex congenita, caregivers, and clinicians and to propose solutions to develop family- and client-centred rehabilitation recommendations.Materials and methods: A modified experience-based co-design methodology was used where qualitative interviews were conducted with key stakeholders.Results: Twenty-seven participants completed the interviews and demographic information was collected where early-active rehabilitation began at birth in most cases and became less frequent through adolescence. Three overarching themes were determined for each stakeholder group.Conclusions: All participants reported that early-active rehabilitation is beneficial as it helps determine future treatments. Transition times and participation need to be at the center of interventions to ensure that the needs of youth with arthrogryposis multiplex congenita are being met. The development a condition-specific outcome-measure and rehabilitation practice recommendations will assist clinicians in addressing the needs of youth with arthrogryposis multiplex congenita.Implications for rehabilitationArthrogryposis multiplex congenita presents in at least two different areas of the body as multiple congenital contractures of varying severity which may affect the upper and lower extremities, spine and jaw.Youth with arthrogryposis multiplex congenita identified participation as an essential component of their life, however caregivers and clinicians did not emphasize this need.Gathering information from different stakeholders is important to ensure varying needs are addressed.Rehabilitation was reported to be beneficial from early childhood to late adolescence by youth, caregivers, and clinicians.Frequency of rehabilitation diminished over time, emphasizing the need for continued follow-up into adolescence.

Development of a research platform for children with arthrogryposis multiplex congenita: study protocol for a pilot registry.

INTRODUCTION: Arthrogryposis multiplex congenita (AMC) describes a heterogeneous group of conditions with multiple congenital contractures. These conditions may be attributed to genetic or other factors inducing decreased fetal movements, including maternal and paternal factors. Discovering the underlying genetic pathways has important repercussions for prevention, gene therapy and genetic counselling. The current literature mainly consists of small-scale, single-site studies, limiting comparability and pooling of findings across individual studies. A pilot registry for children presenting with AMC is proposed to provide the framework for a large-scale AMC registry. This registry will provide the platform to support high-quality studies to inform the distribution, clinical practice and genetics contributing to this group of conditions. METHODS AND ANALYSIS: The registry will be piloted on 40 families of children from birth to 21 years of age presenting with AMC. Data will be collected on the child (demographic and newborn variables), mother and father (demographic, lifestyle habits and medical history). To promote standardised data collection, a manual of operations will be developed. Descriptive statistics will be used to summarise relevant data, regression analyses will be used to explore associations to generate hypotheses regarding factors contributing to AMC. Qualitative analysis will also be used to better describe the various phenotypes. ETHICS AND DISSEMINATION: Ethics approval was obtained at the participating sites. The pilot registry will provide the platform for multisite AMC registry that will generate multiple research avenues to enhance current care and establish new therapies. Following this pilot study, the participant selection criteria will be refined and datasets will be expanded to include rehabilitation and surgical interventions, and genetic sequencing. The best timing for the questionnaire administration and frequency of follow-up prior to the implementation of a multisite AMC registry will be determined.