Orphanet Journal of Rare Diseases

Background and objectives STXBP1-related disorder (STXBP1-RD), caused by pathogenic variants in the STXBP1 gene, is a rare neurodevelopmental condition, characterized by early-onset seizures, developmental delay, intellectual disability (ID), and prominent motor dysfunction. Despite the high prevalence of motor symptoms, systematic gait characterization remains limited. We therefore aimed to quantitively assess gait in individuals with STXBP1-RD. Methods In this cross-sectional study, we include...

BackgroundLiving with multiple long-term conditions (MLTC) is becoming increasingly common with far-reaching consequences for individuals and healthcare systems. People with MLTC often face complex care pathways through health systems - especially hospitals, which are largely configured for specialist treatment of single conditions - yet evidence on people with MLTCs lived experience in the hospital setting is limited. This study aimed to understand the hospital care experiences of people living...

BackgroundCommunication issues across the primary-secondary care interface are considered one of the most important challenges in improving patient safety in primary care in the UK. Teleconferencing offers a potential means of improving communication during referrals but is largely unevaluated. AimTo explore teleconferencing as an alternative to written Advice and Guidance (A&G) referrals for neurology cases, by assessing its impact on GP-specialist communication and relationships, and explorin...

BackgroundMultiple long-term conditions (MLTC) are increasingly common and place significant strain on healthcare systems designed around single-organ conditions, often resulting in fragmented and reactive care for people living with MLTC. There is limited understanding of how health care professionals (HCPs) make decisions for and with individuals with MLTC at the point of hospital presentation. This study examined how HCPs in emergency and acute settings make decisions around pathways and plac...

ObjectivesTo screen the entire genome for genes associated with risk for lateral epicondylopathy and improve understanding of underlying biological mechanisms and inform future research aimed at risk stratification and personalized prevention and treatment strategies. MethodsA genome-wide association study was conducted using UK Biobank data. Lateral epicondylopathy cases were identified based on electronic health records from individuals of European ancestry. Logistic regression tested associa...

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in ageing populations, with oxidative stress recognised as a key pathogenic driver. The dietary antioxidant and cytoprotectant, L-ergothioneine (ET), is avidly accumulated in many tissues, especially the eye. However its relationship to AMD has not been investigated. Here, we examined ETs distribution in ocular tissue and assessed circulating and intraocular ET levels in patients with neovascular AMD. Compared...

BackgroundDystonia is a debilitating movement disorder that is difficult to assess when co-existing with spasticity, as is typical in cerebral palsy (CP). Querying caregivers about their childrens movements is known to increase clinical dystonia identification. However, beyond identification, determining whether dystonia is the predominant vs. accompanying movement feature in a child with CP can guide clinical decision making, particularly regarding surgical candidacy. ObjectiveTo determine whe...

ATP1A3-related syndromes represent a continuously expanding clinical spectrum and present with an extraordinarily wide range of symptoms. New phenotypes continue to emerge, posing ongoing challenges for both diagnosis and development of treatments. In this context, telemedicine offers a unique opportunity to greatly expand outreach to patients. Remote, high-resolution assessments help refine phenotypic characterization and the identification of novel and intermediate phenotypes. In this study w...

BackgroundA Hospital Medicine Advanced Practice Provider (HMAPP)-led care model developed in response to the high acuity and increased patient volumes associated with the Covid-19 pandemic. Although anecdotally perceived as a successful model, questions remained if there was adequate pre-planning and formal implementation strategy for stakeholder buy-in. ObjectiveTo elicit HM physicians and APPs perceptions of the HMAPP-led care model implementation and consider necessary steps for optimal futu...

Protocadherin-12 (PCDH12), a cell-adhesion protein belonging to the non-clustered protocadherin family, plays a crucial role in the establishment and regulation of neuronal connections and communication. Bi-allelic loss-of-function (LoF) variants in the PCDH12 gene have been associated with several neurodevelopmental disorders (NDDs) such as diencephalic-mesencephalic junction dysplasia (DMJD) syndrome, cerebral palsy, and cerebellar ataxia, often accompanied by ocular abnormalities. However, ge...

BackgroundColorectal carcinoma (CRC) remains a significant cause of cancer morbidity and mortality worldwide. Right- and left-sided tumours differ in clinical, morphological, and molecular features. Microsatellite instability-high (MSI-H) tumours, often right-sided, are associated with distinct histopathological characteristics and prognostic implications. In Sri Lanka, molecular MSI testing is currently unavailable, highlighting the need for alternative predictive approaches. ObjectivesGeneral...

ObjectivesFunctional neurological symptoms which do not meet clinical definitions of functional neurological disorder (FND) are common in clinical practice. Understanding the distinction between these benign functional symptoms and FND is crucial in defining FND as an entity for study, and as a clinical syndrome. We aimed to measure the frequency of functional symptoms in people who do not have FND. MethodsA survey was administered to 95 clinicians who attended an international conference on F...

AbstractsO_ST_ABSBackgroundC_ST_ABSSelf-management is essential for stroke survivors to maintain a healthy lifestyle and reduce recurrence risk. Although theory-based self-management interventions are widely recommended, the theoretical frameworks underpinning them and their comparative effectiveness remain unclear. AimsTo systematically identify the theories, models, and frameworks (TMFs) used in self-management interventions for stroke survivors, to explore how they guide interventions, and e...

ObjectiveTo evaluate the criterion-related and discriminant validity, test-retest reliability and minimal detectable difference of The Index of ME Symptoms (TIMES) in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) MethodsPeople with ME/CFS in the UK completed the TIMES online (n=1055). Rasch-transformed interval data and parametric statistics were used: Pearson correlations (with the ME severity scale); analysis of variance; intra-class correlations (ICC) and standard error of meas...

ObjectiveTo develop and psychometrically evaluate an assessment of symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) MethodsAn initial symptom list was devised from the relevant literature with the patient and clinician advisory groups. An online survey with 85 symptom items in eight domains was completed by people with ME/CFS. Each item had two response structures (assessing symptom frequency and severity on five-point scales). Rasch analysis assessed each domain for unid...

BackgroundAlthough ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) are very similar regarding pathophysiology and clinical treatments, especially NSTEMI comprises a much more heterogenic group of patients and underlying diseases. We therefore aimed to assess the treatments and outcomes of both entities in a large contemporary cohort. MethodsPatients with STEMI and NSTEMI between 01/2010 to 12/2018 were identified from the largest German Health Insurance (AOK, {approx}2...

Background: Platform trials are an efficient trial design which enable testing of multiple interventions simultaneously. They could advance knowledge of treatments for intracerebral haemorrhage (ICH). We aimed to investigate the views of clinicians involved in stroke research on recruitment to a future platform trial for ICH. Methods: Between April and July 2025, we conducted a UK-wide online survey of clinicians actively involved in stroke research using convenience sampling through professiona...

Causal discovery algorithms are often leveraged for inferring causal relationships and recovering a causal model from data. However, causal discovery from data alone is limited by the structural constraints of the used dataset, the lack of causal logic, and the lack of external knowledge. Thus, data-driven causal discovery can only suggest possible causal relationships at best. To overcome these limitations, Large Language Models (LLMs) and knowledge systems, such as Retrieval-Augmented Generati...

PurposeWhile genomic testing is integral to pediatric inborn errors of immunity (IEI) care, few studies have examined strategies to support its optimal delivery. This study aimed to characterize a pediatric IEI cohort and assess the impact of implementing a mainstream model-of-care (MoC). Materials/MethodsComprehensive chart audit was conducted for patients ([≤]18y) who received IEI genomic testing in Queensland, Australia, from 2017-2025. Descriptive analyses captured demographic and clinic...

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by reduced expression of the survival motor neuron (SMN) protein. In addition to affecting motor neuron survival, SMN deficiency impacts multisystem physiology and neurotransmission. Dopaminergic dysfunction has been reported in mouse models of SMA, leading to postural and locomotor impairments that improve upon treatment with L-DOPA and benserazide. However, whether altered dopamine metabolism contributes to clinical sympto...