Orphanet J Rare Dis. 2025 Feb 14;20(1):74. doi: 10.1186/s13023-025-03552-3.

ABSTRACT

In a recent publication by Klein et al., the need for real-world data on rare diseases is highlighted. We strongly support this need, and the collaboration with the patient community to collect data, as promoted in this publication. Our concern, however, is that this paper may be misunderstood as suggesting that the Sanofi-run Rare Disease Registries (RDRs) are sufficient to provide the datasets needed to evaluate current and future therapies. Industry-driven registries focus on their own product(s) and, therefore, do not provide the opportunity to compare products from different companies. Today, multiple companies produce treatments for all diseases included in the RDRs. Each company will have to run its own registry for regulatory purposes. This will lead to data fragmentation, which is prohibitive of truly understanding the effects of the various treatment options for these rare diseases. Therefore, independently funded and owned registries are essential to generate real-world evidence (RWE) unrelated to specific products. We discuss options for this for Pompe disease, including the International Pompe Survey, which has collected patient-reported outcomes independently from industry since 2002. This letter aims to raise awareness of the problem of siloed data and advocate for a new way forward where independent registries provide post-marketing surveillance data.

PMID:39953542 | DOI:10.1186/s13023-025-03552-3

J Pak Med Assoc. 2025 Feb;75(2):313-316. doi: 10.47391/JPMA.20212.

ABSTRACT

Gorham-Stout disease is an exceptionally rare disease which is characterised by massive osteolysis of the bone, oedema, and in severe cases pleural effusion and chylothorax. Its aetiopathology is unknown, and no specific treatment has been modulated thus far. We report the case of a 17-year-old male with osteolysis in the bones of his entire left arm and persistent chylothorax. Due to the late presentation and patient's desire for a better quality of life, amputation was the only choice left for treatment. This case was evaluated and treated at the Orthopaedic Surgery and Trauma department of Rehman Medical Institute in Peshawar, Pakistan.

PMID:39948797 | DOI:10.47391/JPMA.20212

J Intellect Disabil Res. 2025 Feb 13. doi: 10.1111/jir.13218. Online ahead of print.

ABSTRACT

BACKGROUND: Dravet Syndrome (DS), Helsmoortel-Van Der Aa Syndrome (HVDAS) and Tuberous Sclerosis Complex (TSC) are rare genetic syndromes, sharing intellectual disability (ID) and motor delay. In DS, two distinct gait patterns, crouch and non-crouch, have been described using instrumented 3D gait analysis (i3DGA). This cross-sectional study measures gait in participants with TSC and HVDAS. The findings are compared to the known crouch and non-crouch gait patterns observed in DS and to typical gait.

METHODS: Participants (6-22 years) with DS (n = 37; 19 crouch and 18 non-crouch), HVDAS (n = 12) or TSC (n = 8) were compared with typically developing (TD) peers (n = 33). All participants underwent i3DGA (Plugin Gait model processed with Vicon Nexus and MATLAB®) to investigate spatiotemporal and lower-limb kinematics.

RESULTS: All three genetic syndromes showed increased step width. Participants with HVDAS and DS, but not participants with TSC walked with decreased step length and velocity compared to TD. HVDAS demonstrated increased knee flexion during the stance phase, lack of hip extension during pre-swing, and increased ankle dorsiflexion during some phases of the gait cycle (p < 0.001). Additionally, HVDAS showed similar kinematic deviations to DS-NonCrouch. No significant differences were found in terms of kinematics between TSC and TD peers (p > 0.05).

CONCLUSION: The current study reveals differences in gait characteristics from typical functional gait in rare genetic disorders. DS-Crouch, DS-NonCrouch and HVDAS display a more impaired gait from a biomechanical perspective than TSC. The variability of clinical and genetic features might explain heterogeneity in gait deviations and should be further explored.

PMID:39948735 | DOI:10.1111/jir.13218

Orphanet J Rare Dis. 2025 Feb 13;20(1):71. doi: 10.1186/s13023-025-03590-x.

ABSTRACT

BACKGROUND: EQ-5D-Y is a pediatric preference-based health-related quality of life (HRQL) measure that is recommended in health economic evaluation according to China's guidelines. However, there is limited evidence regarding how the EQ-5D-Y perform in patients with rare diseases in the country. Neurofibromatosis type 1 (NF1) is a rare disease that affects the growth and development of underage patients. This study aimed to examine the performance of EQ-5D-Y proxy version among underage NF1 patients in China.

METHODS: Data from a nationwide cross-sectional survey from Nov 2022 to Jan 2023 was used. A total of 154 caregivers for underage NF1 patients who completed the EQ-5D-Y proxy version, PedsQL 4.0 Generic Core Scales (PedsQL GCS) proxy version, and Zarit Burden Interview (ZBI-22) were included. The performance of the EQ-5D-Y was assessed by response pattern (ceiling and floor effects), convergent validity against the PedsQL GCS, known-groups validity, and Shannon (H') and Shannon evenness (J') indices.

RESULT: Data from 154 caregivers were analyzed. The mean age of caregivers was 38.23 (6.02) years, and 78.57% of them were mothers of NF1 patients. The mean age of NF1 patients was 8.38 (3.34) years, with 51.30% being females. The ceiling effect of EQ-5D-Y was 30.52%, and floor effect was 0%. Moderate to strong correlations were found between EQ-5D-Y and PedsQL GCS dimensions that share similar constructs (rho - 0.42 to -0.60, all p values < 0.001). The hypotheses of known-groups defined by different PedsQL GCS and ZBI scores were validated. The EQ-5D-Y exhibited the strongest informativity and discriminatory power of the "feeling worried, sad or unhappy" dimension and weakest for the "mobility" dimension (H'(mobility) = 0.60, J'(mobility) = 0.38; H'(feeling worried, sad or unhappy) = 1.23, J'(feeling worried, sad or unhappy) = 0.78).

CONCLUSIONS: EQ-5D-Y is acceptable for measuring HRQL of underage NF1 patients in China. More evidence for using EQ-5D-Y in rare diseases is awaited.

PMID:39948669 | DOI:10.1186/s13023-025-03590-x

Int J Pharm. 2025 Feb 11:125342. doi: 10.1016/j.ijpharm.2025.125342. Online ahead of print.

ABSTRACT

Adrenal insufficiency, an orphan disease, may lead to significant morbidity despite its rare occurrence. Therefore, it requires a daily replacement therapy of hydrocortisone, which displays a highly variable pharmacokinetic profile in individual patients, highlighting the need for personalized dosing. Like most hormones, cortisol follows a circadian rhythm and most conventional dosage forms fail to result in an accurate chronorelease profile. Semi-solid extrusion 3D printing can design unique dosage forms that have the potential to address such needs. Despite several developments and investigations in this area, the existing formulations either fail to facilitate the nocturnal release of cortisol or are unable to meet the personal requirements of patients. Our investigation, thus, focuses on a tablet-in-tablet (core-shell tablet) approach to enable nocturnal release of hydrocortisone and provide personalized dosing. The shell consisted of Klucel™ HF, which acted as rate limiting barrier and provided an initial delayed release of the drug whereas the core comprised of the drug, along with soluble and insoluble diluents, suspended in Klucel™ JF gel. The resulting paste was characterized by its rheology. The optimum parameters for printing both, the core and shell paste were found to be nozzle gauge of 21G, printing speed of 15 mm/s, and the layer height of 0.51 mm. Physicochemical characterization of tablets was conducted with respect to measuring their breaking force, friability, drug content, FTIR, X-ray powder diffraction, SEM, and in-vitro dissolution. This work successfully demonstrates the potential of SSE 3D printing to fabricate Chronotherpeutic release personalized Tablets to improve patient compliance and treatment adherence.

PMID:39947361 | DOI:10.1016/j.ijpharm.2025.125342

Int J Mol Sci. 2025 Jan 31;26(3):1244. doi: 10.3390/ijms26031244.

ABSTRACT

Rare diseases (RDs) often have a genetic basis, yet conventional diagnostic techniques fail to identify causative genetic variations in up to 50% of cases. Structural variants (SVs), including balanced rearrangements, frequently evade detection by karyotyping, microarray, and exome sequencing. The present study utilized optical genome mapping (OGM) to investigate two patients with RDs whose genetic etiology remained unresolved despite prior genomic analyses. Patient 1 exhibited a balanced reciprocal translocation disrupting the BCL11A gene, associated with Dias-Logan syndrome. Patient 2 had a mosaic 682 kb deletion near the IHH gene, causing ectopic enhancer-promoter interactions and polydactyly, mirroring phenotypes observed in mouse models and similar human cases. These findings highlight OGM's efficacy in identifying complex SVs and underline novel pathogenic mechanisms in rare genetic disorders. Consequently, the incorporation of OGM into routine diagnostic procedures will enhance genetic diagnosis, discover new syndromes of currently unknown cause, and eventually improve the clinical management of numerous patients with rare diseases.

PMID:39941010 | DOI:10.3390/ijms26031244

Nutrients. 2025 Jan 26;17(3):455. doi: 10.3390/nu17030455.

ABSTRACT

Background: Telemedicine represents a growing opportunity to improve access to personalized care for patients with rare diseases, addressing the challenges of specialized healthcare that is often limited by geographical barriers. The aim of this narrative review is to explore how telemedicine can facilitate tailored nutritional interventions for rare diseases, focusing on inherited metabolic diseases, rare neurological disorders, such as leukodystrophies, and neuromuscular disorders, including spinal muscular atrophies. Methods: This narrative review is based on a systematic search of the published literature over the past 20 years, and includes systematic reviews, meta-analysis, retrospective studies, and original articles. References were selected through searches in databases such as PubMed and Scopus, applying predefined inclusion and exclusion criteria. Among the inclusion criteria, studies focusing on pediatric patients aged 0 to 18 years, diagnosed with rare neurological diseases or inherited metabolic disorders, and using telemedicine in addition to in-person visits at their reference center were considered. Among the exclusion criteria, studies involving patients with other pathologies or comorbidities and those involving patients older than 18 years were excluded. Results: A total of 66 documents were analyzed to examine the challenges and specific needs of patients with rare diseases, highlighting the advantages and limitations of telemedicine compared to traditional care. The use of telemedicine has revolutionized the medical approach, facilitating integrated care by multidisciplinary teams. Conclusions: Telemedicine still faces several technical, organizational, and security challenges, as well as disparities in access across different geographical areas. Emerging technologies such as artificial intelligence could positively transform the monitoring and management of patients with rare diseases. Telemedicine has great potential ahead of it in the development of increasingly personalized and effective care, in fact, emerging technologies are important to provide remote care, especially for patients with rare diseases.

PMID:39940313 | DOI:10.3390/nu17030455

Arkh Patol. 2025;87(1):28-36. doi: 10.17116/patol20258701128.

ABSTRACT

Dysferlinopathy represents an orphan disease within the spectrum of progressive muscular dystrophies, occurring at a frequency of 1 to 9 cases per 1.000.000 individuals (Orphanet, 2024). It arises from mutations in the DYSF gene (OMIM 603009, 2p13, NM_003494.4), which is responsible for coding the transmembrane protein dysferlin. Dysferlin plays a critical role in the repair of muscle fiber membranes and the cellular processes of skeletal muscle regeneration. Although the molecular mechanisms of dysferlin-mediated repair are under active investigation, reports on the ultrastructural alterations in human skeletal muscles due to dysferlin deficiency are sparse.

OBJECTIVE: To identify the ultrastructural pathomorphological features of skeletal muscles in 6 patients with dysferlinopathy.

MATERIAL AND METHODS: This study presents pathomorphological, immunohistochemical, and ultrastructural data from skeletal muscle biopsies of 6 patients with molecularly confirmed dysferlinopathy.

RESULTS: Examination of paraffin-embedded sections of the anterior tibialis and vastus lateralis muscles, stained with hematoxylin and eosin, identified a primarily myopathic pattern of skeletal muscle injury. Immunohistochemical staining with dysferlin antibodies revealed the absence of the protein in muscle tissue compared to the positive control. Transmission electron microscopy has revealed ultrastructural alterations characteristic of dysferlinopathy, although not specific, including thickening and fragmentation of the basal membrane, thinning and lysis of myofibrils, folding and disruptions of the sarcolemma, destruction of mitochondria, and, newly described in this disease, necrosis of myosatellite cells and telocytes in skeletal muscles.

CONCLUSION: Despite the non-specificity of the identified ultrastructural alterations, electron microscopy of skeletal muscle biopsies in dysferlinopathy can provide additional information about the mechanisms underlying the disease development. The finding of myosatellite cell and telocyte necrosis indicates the impairment of skeletal muscle regenerative capacity, which may be a novel link in the pathogenesis of dysferlinopathy.

PMID:39943726 | DOI:10.17116/patol20258701128

Elife. 2025 Feb 12;13:RP98523. doi: 10.7554/eLife.98523.

ABSTRACT

Endosomes have emerged as major signaling hubs where different internalized ligand-receptor complexes are integrated and the outcome of signaling pathways are organized to regulate the strength and specificity of signal transduction events. Ezrin, a major membrane-actin linker that assembles and coordinates macromolecular signaling complexes at membranes, has emerged recently as an important regulator of lysosomal function. Here, we report that endosomal-localized EGFR/Ezrin complex interacts with and triggers the inhibition of the Tuberous Sclerosis Complex (TSC complex) in response to EGF stimuli. This is regulated through activation of the AKT signaling pathway. Loss of Ezrin was not sufficient to repress TSC complex by EGF and culminated in translocation of TSC complex to lysosomes triggering suppression of mTORC1 signaling. Overexpression of constitutively active EZRINT567D is sufficient to relocalize TSC complex to the endosomes and reactivate mTORC1. Our findings identify EZRIN as a critical regulator of autophagy via TSC complex in response to EGF stimuli and establish the central role of early endosomal signaling in the regulation of mTORC1. Consistently, Medaka fish deficient for Ezrin exhibit defective endo-lysosomal pathway, attributable to the compromised EGFR/AKT signaling, ultimately leading to retinal degeneration. Our data identify a pivotal mechanism of endo-lysosomal signaling involving Ezrin and its associated EGFR/TSC complex, which are essential for retinal function.

PMID:39937579 | DOI:10.7554/eLife.98523

Cien Saude Colet. 2025 Feb;30(2):e07652023. doi: 10.1590/1413-81232025302.07652023. Epub 2023 Nov 6.

ABSTRACT

The scope of this study was to understand the experiences of patients with rare diseases based on the reconstruction of therapeutic itineraries, obtained between 2021 and 2022 using thematic analysis. Common experiences in coping with rare diseases were observed, similar to those referred to globally, perpetuating the vicious circle between specialties, obtaining a diagnosis, post-diagnostic therapies, lack of qualified information and dissemination of knowledge. Arrival at the rare disease reference service revealed a new meaning, based on trust in therapeutic relationships and diagnostic chances, however there was an absence and discontinuity in the provision of some specialties and multidisciplinary therapies. on a continuous basis, providing opportunities in an equal manner. In addition to the need for coordination of care, it was evident that the responsibility for coping with illness is primarily exercised by women, who assume responsibility for the daily therapeutic activities and care of their children. The role of primary care in timely referral and coordination of care in the care network was reaffirmed, promoting equal access and alleviating the burden of management borne by families, which goes beyond and overloads their journey, especially for women.

PMID:39936676 | DOI:10.1590/1413-81232025302.07652023

Rom J Ophthalmol. 2024 Oct-Dec;68(4):466-469. doi: 10.22336/rjo.2024.84.

ABSTRACT

BACKGROUND: Stevens-Johnson syndrome (SJS) is a life-threatening condition resulting from a severe reaction to the use of certain drugs, with the highest incidence found in children. It manifests as a triad of skin, orifice, and ocular mucosa lesions. Ocular manifestations most commonly involve the conjunctiva and eyelids. This case report further discusses symblepharon as an ocular manifestation of SJS.

METHOD: A case report.

CASE REPORT: A 10-year-old boy came with decreased vision and an inability to produce tears. On examination, pseudomembranous conjunctivitis was found in both eyes, granulation tissue in the right eye, and erosion of the corneal epithelium in the left eye. The posterior segment could not be assessed due to symblepharon. It was known that the patient previously experienced SJS in early 2023. Symblepharectomy was carried out with the indication of separate adhesions caused by symblepharon.

DISCUSSION: Symblepharon is a rare, severe ocular manifestation of SJS (Stevens-Johnson syndrome). Previous studies found that severe ocular occurred in around 4% and 11.1% of cases. This happened because of ongoing chronic inflammation due to SJS. Symblepharon is an adhesion of eyelids and bulbar conjunctiva, which can harm the eye because it can cause cicatricial then disruption of the tear film meniscus, limit eye mobility, and cause visual disturbances.

CONCLUSION: Symblepharon occurs due to prolonged inflammation, which can structurally and functionally disrupt the eye. Early discovery of symblepharon, especially in severe manifestations of SJS, can help prevent further damage to the eye.

PMID:39936062 | PMC:PMC11809831 | DOI:10.22336/rjo.2024.84

Orphanet J Rare Dis. 2025 Feb 11;20(1):68. doi: 10.1186/s13023-024-03436-y.

ABSTRACT

BACKGROUND: CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) disease is a newly identified condition with an estimated worldwide prevalence of < 100 patients. Patient interviews can ensure that what is important to patients is assessed in a clinical trial program. Due to the rare and potentially fatal nature of CHAPLE disease, interviews were conducted as part of the pozelimab clinical trial, rather than in a separate study before the trial. The aim of the interviews was to identify the key disease-related signs, symptoms, and health-related quality-of-life (HRQoL) impacts that are important and relevant to patients with CHAPLE disease.

METHODS: Interviews were conducted with patients and/or caregivers at two timepoints (screening and Week 24) during the pozelimab trial to document the signs/symptoms and HRQoL impacts of CHAPLE disease, and document the most bothersome sign/symptom at screening. At Week 24, interviews gathered additional information on the patient experience from caregivers and patients (note: the impact of pozelimab treatment was also collected, though these results are presented elsewhere).

RESULTS: Ten patients, aged 3-19 years, were enrolled in the trial; caregivers contributed to nine interviews. Thirty-one signs‌/symptoms and 65 HRQoL impacts were reported during the interviews. Abdominal pain, diarrhea, facial and peripheral edema/‌swelling, nausea, and vomiting emerged as the core signs/‌symptoms of CHAPLE disease (i.e., experienced by ≥ 90% of patients prior to treatment). The remaining 25 signs/symptoms were experienced by four or fewer (n ≤ 4, ≤ 40.0%) patients, and 15 were only reported by one patient each. Abdominal pain and facial edema were reported as the most bothersome signs/‌symptoms (n = 9, 90.0% and n = 1, 10.0%, respectively). The most frequently reported (i.e., ≥ 80% of interviews) HRQoL impacts were restricted diet (n = 10, 100.0%), sleep disruptions (n = 10, 100.0%), missing school (n = 9, 90.0%), ability to get dressed independently (n = 8, 80.0%), and difficulty engaging in play activities (n = 8, 80.0%).

CONCLUSIONS: The main finding from these patient interviews is the identification of six core signs/symptoms of CHAPLE disease: abdominal pain, diarrhea, facial edema/swelling, peripheral edema/swelling, nausea, and vomiting. The severity of the core signs/symptoms leads to substantial impacts on patients' lives.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT04209634. Registered 20 December 2019 https://classic.

CLINICALTRIALS: gov/ct2/show/NCT04209634 .

PMID:39934837 | DOI:10.1186/s13023-024-03436-y

Sci Data. 2025 Feb 8;12(1):234. doi: 10.1038/s41597-025-04558-z.

ABSTRACT

Although rare diseases (RDs) affect over 260 million individuals worldwide, low data quality and scarcity challenge effective care and research. This work aims to harmonise the Common Data Set by European Rare Disease Registry Infrastructure, Health Level 7 Fast Healthcare Interoperability Base Resources, and the Global Alliance for Genomics and Health Phenopacket Schema into a novel rare disease common data model (RD-CDM), laying the foundation for developing international RD-CDMs aligned with these data standards. We developed a modular-based GitHub repository and documentation to account for flexibility, extensions and further development. Recommendations on the model's cardinalities are given, inviting further refinement and international collaboration. An ontology-based approach was selected to find a common denominator between the semantic and syntactic data standards. Our RD-CDM version 2.0.0 comprises 78 data elements, extending the ERDRI-CDS by 62 elements with previous versions implemented in four German university hospitals capturing real world data for development and evaluation. We identified three categories for evaluation: Medical Data Granularity, Clinical Reasoning and Medical Relevance, and Interoperability and Harmonisation.

PMID:39922817 | DOI:10.1038/s41597-025-04558-z

J Bras Nefrol. 2025 Apr-Jun;47(2):e20240087. doi: 10.1590/2175-8239-JBN-2024-0087en.

ABSTRACT

Atypical hemolytic uremic syndrome (aHUS) is a rare cause of thrombotic microangiopathy (TMA) caused by the dysregulation of the alternative complement pathway. The diagnosis of TMA is made clinically by the triad: microangiopathic hemolytic anemia, thrombocytopenia, and organ damage (mainly acute kidney injury). The heterogeneity of clinical manifestation and the lack of a gold standard diagnostic test makes the precise diagnosis of aHUS a challenging process that may impact patient management. Until one decade ago, there was no specific treatment for aHUS and patients were submitted to plasma therapy (plasma exchange and/or plasma infusion) and/or liver transplantation, procedures that are not free of serious complications and that do not address the underlying pathophysiology of the disease. Since 2011, an anti-C5 complement monoclonal antibody has been approved by the Food and Drug Administration (FDA) for aHUS patients beginning a new era in treatment. Clinical trials on new complement inhibitors may also add to the treatment portfolio in the future. The Brazilian population is a mixed race with a unique genetic and clinical profile. This consensus aims to offer recommendations for the diagnosis and treatment of patients with aHUS in this population based on expert experience, data from the aHUS Brazilian Registry and literature review. The GRADE system was used to classify the quality of the evidence.

PMID:39918340 | DOI:10.1590/2175-8239-JBN-2024-0087en

Eur J Dermatol. 2024 Dec 1;34(6):643-650. doi: 10.1684/ejd.2024.4785.

ABSTRACT

Generalized pustular psoriasis (GPP) is a potentially life-threatening orphan disease. Interleukin (IL)-36 is a known pathogenetic key driver of GPP. The IL-36 receptor inhibitor spesolimab has shown efficacy and safety in clinical trials. However, evidence for spesolimab outside of clinical trials is limited. To provide additional evidence for the use of spesolimab beyond clinical trials, we evaluated individual patient data as part of the spesolimab Compassionate Use Program (CUP) for GPP patients in Germany. Adult patients with an acute GPP flare received 900 mg spesolimab intravenously at baseline and received a second dose on day 8. Data on demographics, efficacy and adverse events were collected from participating sites at baseline, on day 8 and at four weeks. The database included datasets from 12 GPP patients. At baseline, 72% of patients with complete data regarding efficacy (n=7) had a GPPGA (Generalized Pustular Psoriasis Physician Global Assessment) of ≥3, and all patients a PS (pustulation subscore) of ≥3. On day 8, 43% of patients had a GPPGA ≤1 and 72% a PS ≤1. After four weeks, all patients had a GPPGA ≤1 and 86% a PS ≤1. No drug-related adverse events were reported. These findings confirm the results of international, randomized clinical trials in a real-world setting. As spesolimab is no longer available in Germany, this study provides important information that cannot be replicated in this country.

PMID:39912471 | DOI:10.1684/ejd.2024.4785

Front Public Health. 2025 Jan 15;12:1501942. doi: 10.3389/fpubh.2024.1501942. eCollection 2024.

ABSTRACT

INTRODUCTION: Diagnosis, treatment and management of rare diseases (RD) pose unique challenges due to their complex nature, significantly impacting the daily experiences of researchers and healthcare professionals working in this field. Despite increasing awareness and progress in the field of RD worldwide in recent years, a significant gap remains in our understanding of the specific barriers that these professionals face in their work with RD. This study provides a detailed survey analysis that sheds light on the challenges that researchers and healthcare professionals face in diagnosing, treating, managing and conducting research on RD.

METHODS: We developed a national online survey with three RD stakeholder groups (Researchers, Healthcare professionals and researcher-healthcare professionals) to identify the main challenges and needs in Türkiye for the diagnosis, treatment and follow-up processes of rare and undiagnosed diseases.

RESULTS: The survey was completed by 363 participants, revealing that participants face key challenges such as the need to refer patients to specialized centers, financial burdens, limited access to necessary tests, inadequate support for rare disease research and a lack of interdisciplinary collaboration. Participants also noted that RD are inherently difficult to conduct research on with small cohorts. Survey results also suggest a number of policy improvements to accelerate research on RD: increased funding, establishment of robust surveillance systems, and development of comprehensive national action plans and guidelines on RD.

DISCUSSION: To the best of our knowledge, this is the first study to be conducted in Türkiye. This study contributes to the understanding of the needs of professionals in rare disease research and highlights the urgent need for system improvements to support them.

PMID:39911789 | PMC:PMC11795313 | DOI:10.3389/fpubh.2024.1501942

BMC Med Inform Decis Mak. 2025 Feb 5;25(Suppl 1):59. doi: 10.1186/s12911-025-02910-2.

ABSTRACT

BACKGROUND: Virtual Gene Panels (VGP) comprising disease-associated causal genes are utilized in the diagnosis of rare genetic diseases to evaluate candidate genes identified by whole-genome and whole-exome sequencing. VGPs generated by the PanelApp software were utilized in a UK 100,000 Genome Project pilot study to filter candidate genes, thus enhancing diagnostic efficiency for rare diseases. However, PanelApp also filtered out disease-causing genes in nearly 50% of the cases.

METHODS: Here, we propose various methods for optimized approach to design VGPs that significantly improve the diagnostic efficiency by leveraging the hierarchical structure of the Mondo disease ontology, without excluding disease-causing genes. We also performed computational experiments on an evaluation dataset comprising 74 patients to determine the optimal VGP design method.

RESULTS: Our results demonstrate that the proposed method can significantly enhance rare disease diagnosis efficiency by automatically identifying candidate genes. The proposed method successfully designed VGPs that improve diagnosis efficiency without excluding disease-causing genes.

CONCLUSION: We have developed novel methods for VGP design that leverage the hierarchical structure of the Mondo disease ontology to improve rare genetic disease diagnosis efficiency. This approach identifies candidate genes without excluding disease-causing genes, and thereby improves diagnostic efficiency.

PMID:39910609 | DOI:10.1186/s12911-025-02910-2

WMJ. 2024;123(6):619-624.

ABSTRACT

INTRODUCTION: The University of Wisconsin Undiagnosed Disease Program employs a "beyond the exome" approach to diagnose rare disease patients.

CASE PRESENTATIONS: We present 2 cases of rare neurodevelopmental disorders identified by whole genome sequencing. The first is a 12-year-old boy with global developmental delay/intellectual disability (GDD/ID) and congenital hypotonia who was diagnosed with CAPZA2-related disorder. The second is a 13-year-old boy with microcephaly, GDD/ID, and seizures who was diagnosed with neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures (NEDLAS).

DISCUSSION: Our use of whole genome sequencing identified the fifth reported case of CAPZA2-related neurodevelopmental disorder. Fewer than 40 patients have been reported with NEDLAS, and we identified the fourth patient with the AGO1 in-frame deletion p.Glu376del.

CONCLUSIONS: Whole genome sequencing can be effective in diagnosing patients with suspected genetic disorders despite negative standard of care clinical genetic testing and enables the practice of precision medicine.

PMID:39908527

Paediatr Anaesth. 2025 Feb 4. doi: 10.1111/pan.15071. Online ahead of print.

NO ABSTRACT

PMID:39905653 | DOI:10.1111/pan.15071

HNO. 2025 Mar;73(3):203-206. doi: 10.1007/s00106-025-01551-1. Epub 2025 Feb 3.

ABSTRACT

We describe an extremely rare case of a clival mucocele and complement the case report with a literature review. A 30-year-old woman presented to the emergency department with unclear neurologic symptoms after bouldering and left-sided hyposensitivity in her face and radial surface of the forearm. Magnetic resonance imaging was suspicious of a clival mucocele, which was confirmed in computed tomography. Endoscopic drainage of the mucocele was undertaken, after which the patient recovered fully.

PMID:39900815 | DOI:10.1007/s00106-025-01551-1