Calcif Tissue Int. 2025 May 9;116(1):73. doi: 10.1007/s00223-025-01382-w.

ABSTRACT

Transition care (TC) is crucial for young persons with rare bone and mineral conditions (RBMCs) as they move from pediatric to adult healthcare. Effective TC prevents care disruptions and supports medical and psychosocial needs. However, gaps in communication, a shortage of adult RBMC specialists, and challenges in navigating adult healthcare necessitate standardized care. This study aimed to develop consensus-based recommendations for TC in RBMCs, focusing on best practices for seamless transition and patient empowerment. A two-round Delphi survey (September 2023-April 2024) was conducted among European RBMC experts, including 3 pediatric and 8 adult clinicians and 3 patient representatives from the European Calcified Tissue Society (ECTS). The panel formulated and refined statements through literature review and iterative scoring. Statements reaching ≥ 70% consensus were retained. A total of 81 statements were finalized across seven domains: initiation and planning, TC requirements, patient empowerment, organization and communication, service infrastructure and funding, and clinical care. Consensus was achieved on 64 out of 81 statements, with strong agreement on general and RBMC-specific recommendations. Key priorities included structured coordination among healthcare providers and a patient-centered approach that fosters self-advocacy and self-management. This Delphi consensus provides a structured framework for TC in young persons with RBMCs, emphasizing multidisciplinary care and patient empowerment. Future studies should assess the feasibility and impact of these guidelines across diverse healthcare systems.

PMID:40346280 | DOI:10.1007/s00223-025-01382-w

Nurs Clin North Am. 2025 Jun;60(2):349-368. doi: 10.1016/j.cnur.2024.12.005. Epub 2025 Mar 3.

ABSTRACT

Rare diseases (RDs) are predominantly genetic in etiology and characterized by low frequency and high medical complexity. Although individually infrequent, the cumulative public health impact of ∼7000 RDs is significant, and patients and families experience significant psychosocial burden. Health disparities stem from delays in diagnosis (diagnostic odyssey), difficulty accessing care, and lack of effective treatments. This article provides an overview of rare genetic diseases and highlights exemplar cases demonstrating nursing's role in advancing comprehensive, person-centered care for rare genetic diseases. Resources and recommendations are provided for nurses to enhance quality care for individuals and families living with RDs.

PMID:40345765 | DOI:10.1016/j.cnur.2024.12.005

Funct Integr Genomics. 2025 May 9;25(1):101. doi: 10.1007/s10142-025-01608-y.

ABSTRACT

Mulvihill-Smith Syndrome (MSS) is a clinically complex and genetically unsolved nano-rare disorder with only 12 patients reported in the literature. Most patients (91%) have immunological impairments, succumb to infection, and might develop cancer later in life. Its pathogenesis remains elusive and therapeutic options are limited. We used single-cell MULTI-omics (sc-MULTI-omics), combining transcriptomics (gene expression, TCR, and BCR repertoire) and proteogenomic (Cellular Indexing of Transcriptomes and Epitopes by Sequencing; CITE-seq), to decipher the pathophysiology of nano-rare disease patient. We report a new patient who is a 16-year-old girl. She had an increased leukocyte counts and typical manifestations of MSS such as short stature, older appearance, multiple pigmented nevi, microcephaly, monolateral keratoconus, Marcus-Gunn syndrome, hearing loss, vitamin D deficiency, mild hypercortisolism, and diabetes mellitus with very high insulin resistance (T3DM). sc-MULTI-omics CITE-seq showed that the MSS patient had increased central memory CD4+ T cells as well as effector memory CD8+ T cells, whilst reduced naïve T cells (both CD4+ and CD8+ T cells). Furthermore, we identified genes and pathways associated with the progeria-like phenotype, inflammation, and cancer progression, which may contribute to the clinical signs of MSS. sc-MUTLI-omics CITE-seq analyses improve our understanding of complex human disease pathophysiology and provides an alternative approach in personalized medicine in nano-rare disease.

PMID:40343591 | DOI:10.1007/s10142-025-01608-y

Am Soc Clin Oncol Educ Book. 2025 Jun;45(3):e473106. doi: 10.1200/EDBK-25-473106. Epub 2025 May 8.

ABSTRACT

Rare uterine malignancies present treatment challenges because of their clinical and biological heterogeneity. Among the rarest of the uterine cancers are leiomyosarcomas, uterine stromal tumors, and the mesonephric-like and serous carcinomas. In this article, we review recent advancements in diagnostic precision, risk stratification, and identification of biomarker-guided therapeutic options for these rare subtypes of uterine tumors. The improved understanding of the molecular profile of these tumors has led to the development of targeted treatment approaches. Further progress will depend on a coordinated, global effort to further characterize these diseases and enroll patients on biomarker-driven clinical trials.

PMID:40340459 | DOI:10.1200/EDBK-25-473106

Rev Med Interne. 2025 May;46(5):287-292. doi: 10.1016/j.revmed.2025.03.424. Epub 2025 May 5.

ABSTRACT

This review describes the role of real-world data (RWD) at each step of drug development for rare diseases like immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). We also describe the main sources of RWD in rare diseases and how the generation of real-world evidence (RWE) is crucial for decisions of regulatory health agencies regarding drugs for rare disease.

PMID:40328530 | DOI:10.1016/j.revmed.2025.03.424

JAMA Netw Open. 2025 May 1;8(5):e258330. doi: 10.1001/jamanetworkopen.2025.8330.

ABSTRACT

IMPORTANCE: Treatments are urgently needed for the more than 9500 rare diseases with no US Food and Drug Administration-approved therapies. Although repurposing can be less time- and cost-intensive compared with novel drug development, hurdles have impeded systematic repurposing. Rare disease nonprofit organizations (RDNPs) are well-positioned to overcome barriers and have spearheaded rare disease repurposing efforts for decades. However, no comprehensive data are available on the state of rare disease repurposing or features of successful efforts.

OBJECTIVE: To characterize the state of rare disease drug repurposing, identify factors associated with successful outcomes, and share thematic insights using the interactive Repurposing of All Drugs, Mapping All Paths (ROADMAP) Project web tool.

DESIGN, SETTING, AND PARTICIPANTS: The ROADMAP study was a qualitative study using a mixed-methods analysis of US-based RDNP leaders and their stakeholders, including a national survey and semistructured interviews of RDNP leaders, conducted from September 29, 2021, to January 6, 2022. Surveys and interviews revealed themes associated with RDNP strategies, timelines, and support mechanisms. Data were analyzed from January 22, 2024, to April 23, 2024.

MAIN OUTCOMES AND MEASURES: The primary survey outcome was the repurposing project stage (abandoned, early, clinical, late, or successful). Qualitative outcomes included themes characterizing repurposing experiences. Two random forest models of drug- and disease- specific as well as organization-specific variables were used to evaluate factor importance toward inferring the project stage. Orthogonal significance testing was conducted using Spearman rank correlation, and P values in each model were corrected for multiple hypothesis testing using a Benjamini-Hochberg procedure.

RESULTS: Representative organizations submitted survey responses, including 147 of 698 potential US-based RDNPs. The median RDNP age was 10 years (IQR, 5-20 years), and the median annual revenue was $355 390 (IQR, $90 028-$946 108). Among 34 leaders who were interviewed, representing 25 RDNPs, 23 were female (67.6%), and the RDNPs had a median age of 15 years (IQR, 6-19 years) and a median revenue of $670 719 (IQR, $193 587-$1 830 890). Among the surveyed RDNPs, 58 of 138 (42.0%) specifically identifying their involvement in repurposing supported repurposing projects, and 94 drugs were in various stages of repurposing, of which 23 met success criteria (5 with US Food and Drug Administration approval and 18 with off-label use with subjective benefit). Survey factors associated with successful outcomes included nonprofit-supported patient recruitment into trials (Gini importance, 3.90; ρ = 0.50; adjusted P < .001) and provision of nonfinancial research support (Gini importance, 0.69; ρ = 0.33; adjusted P = .02). Interview themes were synthesized into a 5-stage repurposing framework with roadblocks and recommendations that included (1) enabling drug repurposing, (2) identifying a drug therapy, (3) validating a drug therapy, (4) clinical use and testing, and (5) reaching an optimal end point for clinical practice.

CONCLUSIONS AND RELEVANCE: The findings of this qualitative study of RDNP repurposing suggest that several opportunities were associated with successful outcomes and can be considered to optimize systematic repurposing among RDNPs, external collaborators, and policymakers with the use of an interactive tool showcasing insights to facilitate data-driven drug repurposing.

PMID:40323602 | DOI:10.1001/jamanetworkopen.2025.8330

Int J Med Inform. 2025 Sep;201:105942. doi: 10.1016/j.ijmedinf.2025.105942. Epub 2025 Apr 21.

ABSTRACT

OBJECTIVE: Dravet Syndrome (DS) is a developmental and epileptic encephalopathy that is characterized by severe, prolonged motor seizures and high resistance to multiple antiseizure medications (ASMs) with multiple comorbidities. Evaluating the efficacy of new drugs in DS preclinical models and mapping them to human phenotypes of DS through analysis of published literature is an important goal for improving outcomes in this rare pediatric epilepsy.

MATERIALS AND METHODS: Large language models (LLM) have demonstrated great promise in parsing published literature; however, the performance of LLMs falls short in medical applications. In this study, we investigate the effectiveness of domain ontology developed by human experts to optimize LLMs for medical text processing in a rare disease. Utilizing a benchmark dataset that describes the efficacy of 17 ASMs tested in preclinical models and DS patients, we define a new ontology-augmented phased in-context learning (PCL) approach to process 4935 full-text DS articles. We expand this analysis to 7 new drugs that demonstrate efficacy in reducing seizures to identify gaps in current knowledge for designing new experimental studies for drug discovery in DS.

RESULTS: Few-shot or in-context learning is a foundational capability of LLMs and the few-shot learning capability of the Gemini 1.0 Pro version LLM dramatically increases when we augment prompts with the DS epilepsy ontology. The DS epilepsy ontology is the largest epilepsy and seizure ontology in clinical use that was developed by DS basic scientists and clinical neurologists. The ontology-augmented PCL prompt achieves 100% accuracy in reproducing the benchmark drug efficacy dataset for 17 ASMs with only two examples for in-context learning.

CONCLUSION: The new ontology-augmented PCL approach significantly accelerates the few-shot learning capabilities of the Gemini LLM, thereby reducing the number of required examples and time needed to optimize LLMs for medical applications.

PMID:40311258 | DOI:10.1016/j.ijmedinf.2025.105942

Cancer Radiother. 2025 Apr 30;29(2):104622. doi: 10.1016/j.canrad.2025.104622. Online ahead of print.

ABSTRACT

PURPOSE: Lung cancers associated with interstitial lung disease are challenging to diagnose and manage. We investigated the prevalence of interstitial lung disease among consecutively irradiated cancer patients, and the tolerance and prognosis of patients with or without interstitial lung disease after thoracic radiotherapy.

MATERIAL AND METHODS: This bicentric study was designed as a case-control study of patients with interstitial lung disease prior to radiotherapy (cases) and controls without interstitial lung disease. Patients were irradiated with curative intent for localized, locally advanced or oligometastatic non-small cell lung cancer. Consecutive lung cancer patients undergoing curative radiotherapy between January 2018 and December 2020 had centralized review of their baseline and 6-month CT scans by a multidisciplinary board. Functional evaluation, radiological scores, clinical toxicities, best objective response, progression-free survival and overall survival were assessed.

RESULTS: Twelve cases were detected out of 166 patients (7.2 %), including six diagnosed a posteriori by central review (50 %). Initial patient, tumour and lung cancer treatment characteristics were similar between cases and controls except for performance status (P=0.004), Kazerooni scores of fibrosis and ground glass patterns (P<0.001). Cases and controls underwent three-dimensional radiotherapy in 0 and 37 (24.2 %), intensity-modulated radiotherapy in eight (66.7 %) and 60 (39.2 %), stereotactic body radiotherapy in four (33.3 %) and 56 (36.6 %), respectively (P=0.079). Grade≥2 pneumonitis occurred in 41.7 % of cases versus 11 %, of controls (P=0.01). Hospitalization rates were 16 % in cases versus 2 % in controls and one case died of lung toxicity. Best objective response was worse for cases (P=0.046). Median progression-free survival was 9.35 months for cases and 18.56 months for controls. Median overall survival was 17 months for cases and not reached for controls (P=0.002). Sex, tumour stage, histology, and interstitial pulmonary fibrosis were prognostic factors for overall survival on univariate analysis.

CONCLUSION: Interstitial lung disease was present in 7 % of the patients with lung cancer. Patients with interstitial lung disease had higher risks of toxicity events and poorer prognosis, suggesting the lungs should be assessed carefully and that specific management strategies are warranted.

PMID:40311519 | DOI:10.1016/j.canrad.2025.104622

J Genet Couns. 2025 Jun;34(3):e70015. doi: 10.1002/jgc4.70015.

ABSTRACT

In recent years, an increasing number of affected children have been diagnosed through whole-exome sequencing (WES); however, it remains unclear whether the problems faced by the patients' parents during the undiagnosed period were resolved. This exploratory qualitative study aimed to clarify the needs of the parents of children who have been diagnosed with rare genetic diseases and determine the factors that may help provide the environment necessary for the family to understand and accept the symptoms and characteristics associated with the disease and live with their affected child. Semi-structured interviews were conducted with the parents of children (less than 18 years old) who participated in a research project, namely the Initiative on Undiagnosed and Rare Diseases (IRUD), at Kyoto University Hospital between November 2016 and December 2021. A reflective thematic analysis generated three themes: the benefits of diagnosis from the perspective of parents, the challenges to be solved after diagnosis, and the significance and issues of revealing genetic information. The results showed that the diagnoses provided psychological satisfaction for the parents. However, diagnosis of a hereditary and rare disease can lead to social and medical isolation, and it was necessary to improve the environment around the affected children's families, mainly by taking advantage of the IRUD research system. The analysis indicated the need for psychological support, which can be provided by the clinical genetic department, the need for a follow-up system in collaboration with various clinical departments, and the need to improve the general public's understanding of human genetics.

PMID:40305385 | DOI:10.1002/jgc4.70015

Sci Rep. 2025 Apr 29;15(1):15093. doi: 10.1038/s41598-025-99539-y.

ABSTRACT

Computational methods for identifying gene-disease associations can use both genomic and phenotypic information to prioritize genes and variants that may be associated with genetic diseases. Phenotype-based methods commonly rely on comparing phenotypes observed in a patient with databases of genotype-to-phenotype associations using measures of semantic similarity. They are constrained by the quality and completeness of these resources as well as the quality and completeness of patient phenotype annotation. Genotype-to-phenotype associations used by these methods are largely derived from the literature and coded using phenotype ontologies. Large Language Models (LLMs) have been trained on large amounts of text and data and have shown their potential to answer complex questions across multiple domains. Here, we evaluate the effectiveness of LLMs in prioritizing disease-associated genes compared to existing bioinformatics methods. We show that LLMs can prioritize disease-associated genes as well, or better than, dedicated bioinformatics methods relying on pre-defined phenotype similarity, when gene sets range from 5 to 100 candidates. We apply our approach to a cohort of undiagnosed patients with rare diseases and show that LLMs can be used to provide diagnostic support that helps in identifying plausible candidate genes. Our results show that LLMs may offer an alternative to traditional bioinformatics methods to prioritize disease-associated genes based on disease phenotypes. They may, therefore, potentially enhance diagnostic accuracy and simplify the process for rare genetic diseases.

PMID:40301638 | DOI:10.1038/s41598-025-99539-y

J Manag Care Spec Pharm. 2025 May;31(5):491-498. doi: 10.18553/jmcp.2025.31.5.491.

ABSTRACT

BACKGROUND: More than 10,000 rare diseases affect more than 30 million Americans, nearly 70% of which manifest in childhood. The drug development pipeline boasts hundreds of candidates for pediatric-onset rare disease, but little is known about the impact of potential approvals.

OBJECTIVE: To quantify US projected product approvals, patients treated, and product revenues for pediatric-onset rare disease treatments through 2033.

METHODS: Four-stage model consisting of a Markov Chain Monte Carlo simulation of US Food and Drug Administration approvals, calculation of eligible patients per clinical trial criteria, and projection of adoption and list price revenues, all using publicly available data.

RESULTS: By 2033 the pipeline will yield approximately 45 new product approvals, a 14% growth in annual treated patients, and an incremental $10.7B in list price drug revenues ($28.2B: 2023; $38.9B: 2033) prior to any health care cost offsets, caregiving impacts, long-term social benefits, or other benefits from treating the additional patients.

CONCLUSIONS: The projected approvals over the next decade will undoubtedly be transformational for the patient communities impacted, many of whom have no currently approved treatments. However, the number of newly identified rare diseases is likely to outpace the rate of new therapies to treat them. Resources are needed to accelerate progress as 95% of pediatric-onset rare diseases are projected to still have no approved treatments in the next decade, and even for the 5% that have some options, more is needed.

PMID:40298308 | DOI:10.18553/jmcp.2025.31.5.491

Psychiatry Res. 2025 Jul;349:116509. doi: 10.1016/j.psychres.2025.116509. Epub 2025 Apr 19.

ABSTRACT

People presenting to centres for rare diseases (CRD) for diagnostic work-up often suffer from mental disorders. The prevalence and distribution of these mental disorders and their relevance for care remain largely unclear and well-controlled multicentre studies are missing. The ZSE-DUO study was a multicentre, prospective, controlled cohort study involving 11 German CRD. In total, 662 adult patients with an unclear diagnosis were evaluated by an additional mental health specialist along with their usual CRD care. Mental disorders were assessed through a standardized clinical examination, including the Mini-DIPS interview. Prevalence of diagnosed mental disorders (ICD-10 coding) was assessed and compared to population prevalence. A total of 54.5 % (361 patients) of adults with unexplained symptoms presenting to a CRD had current mental disorders. Mental disorders were deemed the sole explanation for the entire symptomatology in 53.5 % of cases. In 36.2 % of cases, a combination of a mental disorder with a somatic disease was considered to explain the unexplained symptoms. In 8.3 % of cases, it was assessed that the mental disorder was not involved in explaining the unexplained symptoms. Assessing whether a mental disorder contributes to the patient's symptom complex is crucial for determining suitable treatment strategies in terms of a bio-psycho-social approach.

PMID:40286780 | DOI:10.1016/j.psychres.2025.116509

BMC Med Res Methodol. 2025 Apr 26;25(1):114. doi: 10.1186/s12874-025-02559-5.

ABSTRACT

INTRODUCTION: Rare events data have proven difficult to explain and predict. Standard statistical procedures can sharply underestimate the probability of rare events, such as intravenous immune globulin therapy (IVIg) for bullous pemphigoid.

METHODS: This retrospective cross-sectional study used Department of Defense TRICARE data to determine factors associated with IVIg therapy among bullous pemphigoid patients. We used prior and weighted correction methods for logit regression to solve rare event bias.

RESULTS: We identified 2,720 individuals diagnosed with bullous pemphigoid from 2019 to 2022, of which 14 were treated with IVIg. Patients who received IVIg therapy were younger (65.07 vs. 75.85, P =.0016) and more likely to be female (13 vs. 1, P =.0036). The underestimation with the standard regression model for event probabilities ranged from 11% to 102% using the prior correction method and from 15% to 107% using the weighted correction method.

CONCLUSION: Rare events are low-frequency, high-severity problems that can have significant consequences. Rare diseases and rare therapies are individually unique but collectively contribute to substantial health and social needs. Therefore, correct estimation of the events is the first step toward assessing the burden of rare diseases and the pricing of their therapies.

PMID:40287629 | DOI:10.1186/s12874-025-02559-5

Pharmaceutics. 2025 Mar 31;17(4):450. doi: 10.3390/pharmaceutics17040450.

ABSTRACT

The mRNA- and DNA-based "genetic" COVID-19 vaccines can induce a broad range of adverse events (AEs), with statistics showing significant variation depending on the timing and data analysis methods used. Focusing only on lipid nanoparticle-enclosed mRNA (mRNA-LNP) vaccines, this review traces the evolution of statistical conclusions on the prevalence of AEs and incidents associated with these vaccines, from initial underestimation of atypical, severe toxicities to recent claims suggesting the possible contribution of COVID-19 vaccinations to the excess deaths observed in many countries over the past few years. Among hundreds of different AEs listed in Pfizer's pharmacovigilance survey, the present analysis categorizes the main symptoms according to organ systems, with nearly all of them being affected. Using data from the US Vaccine Adverse Event Reporting System and a global vaccination dataset, a comparison of the prevalence and incidence rates of AEs induced by genetic versus flu vaccines revealed an average 26-fold increase in AEs with the use of genetic vaccines. The difference is especially pronounced in the case of severe 'Brighton-listed' AEs, which are also observed in COVID-19 and post-COVID conditions. Among these, the increases in incidence rates relative to flu vaccines, given as x-fold rises, were 1152x, 455x, 226x, 218x, 162x, 152x, and 131x for myocarditis, thrombosis, death, myocardial infarction, tachycardia, dyspnea, and hypertension, respectively. The review delineates the concept that genetic vaccines can be regarded as prophylactic immuno-gene therapies and that the observed chronic disabling AEs might be categorized as iatrogenic orphan diseases. It also examines the unique vaccine characteristics that could be causally related to abnormal immune responses which potentially lead to adverse events and complications. These new insights may contribute to improving the safety of this platform technology and assessing the risk/benefit balance of various products.

PMID:40284445 | DOI:10.3390/pharmaceutics17040450

Int J Tuberc Lung Dis. 2025 May 25;29(5):199-201. doi: 10.5588/ijtld.25.0157.

ABSTRACT

Until relatively recently, bronchiectasis (not due to cystic fibrosis) was considered an orphan disease, lacking clinical and commercial interest, and was rarely diagnosed. Since the 2000s, several working groups have emerged in Europe and the US - with the first register for bronchiectasis launching in Spain - and these have demonstrated the impact bronchiectasis has on health. Today, bronchiectasis is considered the third most common chronic inflammatory disease of the airways, after COPD and asthma, and represents a significant economic burden. We make the case for further characterization of these registries to better understand the heterogeneous epidemiology of bronchiectasis.

PMID:40281677 | DOI:10.5588/ijtld.25.0157

Trends Cardiovasc Med. 2025 Apr 23:S1050-1738(25)00052-0. doi: 10.1016/j.tcm.2025.04.003. Online ahead of print.

NO ABSTRACT

PMID:40280353 | DOI:10.1016/j.tcm.2025.04.003

Nucleic Acids Res. 2025 Apr 22;53(8):gkaf346. doi: 10.1093/nar/gkaf346.

ABSTRACT

Developing customized gene-targeting therapies for the millions of individuals affected by ultra-rare diseases globally requires breaking new ground in therapeutic and regulatory innovation. To address this need, the N=1 Collaborative (N1C) was established to unite academia, industry, patients, and regulators, building an open, shared ecosystem for personalized medicines. Initially focusing on antisense oligonucleotides (ASOs) for rare, fatal neurodegenerative conditions, the N1C aims to develop frameworks that can rapidly extend to other treatment modalities and conditions. Progress in the advancement of personalized therapies has also propelled advancements in the nucleic acids field, offering critical insights into dosing, safety, and efficacy. In October 2024, the N1C convened scientific, regulatory, and advocacy leaders in ASO development for an inaugural meeting. This review report examines the current state of the scientific and clinical ecosystems enabling customized genetic therapies and explores the innovation, frameworks, and systems needed to deliver additional individualized medicines safely and at scale.

PMID:40277082 | DOI:10.1093/nar/gkaf346

Inn Med (Heidelb). 2025 May;66(5):533-539. doi: 10.1007/s00108-025-01892-7. Epub 2025 Apr 24.

ABSTRACT

Rare diseases, defined in the European Union as conditions affecting fewer than five per 10,000 inhabitants, often manifest themselves in childhood, but are playing an increasingly important role in internal medicine due to the significantly improved long-term prognosis and a number of diseases that primarily occur in adulthood. Although noteworthy structures already exist nationally and internationally (networks, registers, databases, self-help groups), awareness of these diseases in daily routine and knowledge of the partly divergent care structures must be improved. There are no specific treatments for many of these diseases, but drugs are increasingly being developed-particularly in oncology-that are subject to special orphan drug status.

PMID:40272470 | DOI:10.1007/s00108-025-01892-7

Indian J Ophthalmol. 2025 May 1;73(5):622-636. doi: 10.4103/IJO.IJO_1542_24. Epub 2025 Apr 24.

ABSTRACT

Rare pediatric retinal disorders present significant challenges in diagnosis and management due to their limited prevalence and diverse clinical manifestations. This paper provides a comprehensive review of select rare retinal disorders affecting the pediatric population, focussing a brief on their epidemiology, clinical characteristics, diagnostic modalities, and therapeutic interventions. Through a systematic examination of current literature and clinical case studies, this review aims to elucidate the distinct features and challenges associated with each disorder. Despite the rarity of these conditions, their impact on visual function and quality of life necessitates heightened awareness among clinicians and researchers to facilitate timely diagnosis, appropriate management, and improved outcomes for affected children as their visual systems are still developing. Furthermore, advancements in diagnostic modalities such as fundus fluorescein angiography, optical coherence tomography, electroretinography, and genetic testing are examined for their role in enhancing our understanding of rare pediatric retinal disorders and facilitating early intervention strategies. The literature selection for this article was conducted through PubMed, Google Scholar, and the Cochrane Library databases. A thorough systematic search was carried out for the concerned diseases. Relevant review articles, original research studies, case series, and reports were examined. Additionally, references from these sources were reviewed and included if they provided pertinent information on the topic. The search was not restricted by publication date.

PMID:40272290 | DOI:10.4103/IJO.IJO_1542_24

Orphanet J Rare Dis. 2025 Apr 23;20(1):193. doi: 10.1186/s13023-025-03691-7.

ABSTRACT

BACKGROUND: The socioeconomic impact of rare diseases has been mostly studied at the macrolevel, but evidence at the microlevel is lacking, which overshadows health-related social inequalities affecting people with rare diseases, namely, health selection effects.

AIM: This study presents an overview of employment and work ability in individuals living with rare diseases, two factors related to health selection effects.

METHODS: A systematic literature review was conducted using the PRISMA checklist. Three electronic databases, PubMed, Embase, and Web of Science, were searched from 2013 to 2023. Eligible studies needed to investigate at least one work-related outcome measuring employment or work ability in individuals living with rare diseases and to compare it with a control group. Indeed, including only studies with matched or standardized control groups is essential for ensuring the reliability and validity of research findings.

RESULTS: Of the 7,694 abstracts identified, 44 studies, including 34 rare diseases, met the inclusion criteria. Administrative databases were used to collect work-related data in 48% of the studies, and 73% of the studies employed matching methods for comparison. Overall, 52% of the studies focused solely on employment, 14% focused solely on work ability and 34% included both categories. Individuals with rare diseases were less likely to be employed or more likely to be unemployed than controls in 68% of the studies and 87% of the studies reported that individuals with rare diseases were more likely to be work disabled. Regarding work ability, 90% of the studies reported more missed work time in cases than in controls, and more perceived impairment at work was found in 100% of the studies.

DISCUSSION/CONCLUSION: These results show that individuals with rare diseases tend to have poor work outcomes, but methodological limitations hamper the understanding of health selection effects. Implications for future research and policy-making are discussed.

PMID:40270029 | DOI:10.1186/s13023-025-03691-7