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...

In LGMDR1-Calpain-3 related, as in all muscular dystrophies, clinical trial monitoring remains a challenge due to the lack of reliable biomarkers. This study assessed IL-32 concentrations in both serum and urine, uncovering a marked increase in patients compared to healthy controls. Serum IL-32 levels were especially elevated in young adults, suggesting a possible link to the early and more active phases of disease onset. Meanwhile, urinary IL-32 levels showed consistent elevation across all age...

BackgroundAberrant myelination represents a critical but understudied mechanism in cognitive difficulties associated with neurodevelopmental conditions. Neurofibromatosis 1 (NF1), provides a unique monogenic model to investigate this relationship, as white matter abnormalities are consistently observed, yet their microstructural basis remains uncharacterized. We present the first dual-modality quantitative myelin mapping study in NF1, employing Magnetization Transfer and T1W/T2W ratio imaging to...

Leber hereditary optic neuropathy (LHON) is primarily caused by pathogenic mitochondrial DNA (mtDNA) variants, most commonly the m.11778G>A variant in the MT-ND4 gene. The presence of this variant alone is insufficient to trigger disease symptoms, of which vision loss is the hallmark. Given the incomplete penetrance and inter-population variability in modifying factors, this study aimed to investigate two previously proposed genetic risk factors for LHON in the Polish population. Using quantitat...

PurposeMyasthenia gravis (MG) is a rare neuromuscular disease. In-person appointments in specialized centers are not readily available, especially on short notice. The purpose of this study was to analyze patient-specialist communication through a telemedical platform. MethodsIn a randomized controlled study 45 MG patients were observed over three months. The intervention group (N=30) was monitored via a mobile application ( app) that enabled chat function and assessed MG-specific outcome measu...

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...

Patients with amyotrophic lateral sclerosis (ALS) often experience dysphagia, leading to malnutrition and weight loss. Percutaneous endoscopic gastrostomy (PEG) tubes help address these issues, but complications and limited patient education may diminish their benefits. This project evaluated the patient experience from an educational pamphlet created by a multi-disciplinary team at our academic centers ALS Clinic. The pamphlet was distributed at the time of PEG placement and covered tube functi...

ObjectiveDuchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder for which monitoring biomarkers are urgently needed. We aimed to evaluate whether proteins in serum can accurately monitor patients function within the duration of a clinical trial. MethodsIn this study, we evaluated longitudinal serum proteins of DMD patients participating to the FOR-DMD clinical trial, comparing daily and intermittent corticosteroid regimens in boys aged 4-8 years at baseline. Using the aptamer...

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...

IntroductionVestibular schwannoma (VS) is a benign tumor of the vestibulocochlear nerve, often causing hearing loss, balance disturbances, and psychosocial challenges. While surgical resection is standard, the long-term biopsychosocial impact of surgery is poorly understood. Research questionWhat are the physical, psychological, and social challenges experienced by patients up to five years after VS surgery? Material and MethodsA qualitative study was conducted using semi-structured video call...

PURPOSEBEST1-associated inherited retinal disease constitutes one of the largest inherited retinal disease patient populations across the world. Innovative therapies are currently in development to address this significant unmet need. To better understand the scale of unmet need, and the distribution of phenotypes and genotypes, we conducted a meta-analysis of BEST1 patients reported in the literature to provide up-to-date patient number estimates. METHODSWe utilized the GeneScape(R) IRD Patien...

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...

1PurposeThe KIND (KINder mit Diabetes) cohort investigates diabetic peripheral neuropathy (DPN) in paediatric type 1 diabetes (T1D). Current guidelines recommend DPN screening at puberty or from 11 years and 2-5 years after T1D diagnosis, yet subclinical neurophysiological changes occur within the first 2 years. The cohort examines: (1) longitudinal associations between glycaemic metrics (HbA1c and continuous glucose monitoring-derived variability metrics) and peripheral nerve function and struc...

BackgroundThe Canadian Guidelines for Post COVID-19 Condition (CAN-PCC), along with related knowledge mobilization (KM) resources, have been developed to support key interest-holders (e.g., public, healthcare providers, and policymakers) to make informed health decisions related to post COVID-19 condition (PCC). The purpose of this report is to describe the process and findings of our usability testing with members of the public on eight public-facing KM resources to support the CAN-PCC guidelin...

BackgroundDuring the COVID-19 pandemic, Ontario implemented a self-triage tool that assessed risk and directed users to care. Screening for entry to workplaces and schools was provincially mandated, allowing for adaptation to specific needs, often implemented with digital symptom checkers. Thus, self-assessment tools that looked similar, may have varied in purpose, and possibly in assessment criteria. ObjectiveThis study asks: what can we learn from family medicine providers experiences with, a...

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...

Persistent Postural-Perceptual Dizziness (PPPD) is among the most prevalent chronic neuro-otologic disorders, affecting 15-20% of adults seen in neurology and specialized dizziness clinics. Classified as a functional vestibular disorder and defined by established diagnostic criteria, PPPD typically follows peripheral or central otoneurological disorders. However, the mechanisms underlying the transition from these disorders to chronic perceptual dizziness remain unclear. Beyond maladaptive postu...

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...