medRxiv [Preprint]. 2025 Feb 18:2025.02.16.25322147. doi: 10.1101/2025.02.16.25322147.

ABSTRACT

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a poorly understood and underdiagnosed syndrome of chronic bladder/pelvic pain with urinary frequency and urgency. Though IC/BPS can be hereditary, little is known of its genetic etiology. Using the eMERGE data, we confirmed known phenotypic associations such as gastroesophageal reflux disease and irritable bowel syndrome and detected new associations, including osteoarthrosis/osteoarthritis and Barrett's esophagus. An exome wide ultra-rare variants analysis in 348 IC/BPS and 11,981 controls extended the previously reported association with ATP2C1 and ATP2A2, implicated in Mendelian desquamating skin disorders, but did not provide evidence for other previously proposed pathogenic pathways such as bladder development, nociception or inflammation. Pathway analysis detected new associations with "anaphase-promoting complex-dependent catabolic process", the "regulation of MAPK cascade" and "integrin binding". These findings suggest perturbations in biological networks for epithelial integrity and cell cycle progression in IC/BPS pathogenesis, and provide a roadmap for its future investigation.

PMID:40034785 | PMC:PMC11875234 | DOI:10.1101/2025.02.16.25322147

IEEE J Biomed Health Inform. 2025 Mar;29(3):2161-2171. doi: 10.1109/JBHI.2024.3500094. Epub 2025 Mar 6.

ABSTRACT

The automated diagnosis of rare skin diseases using dermoscopy images, known as a few-shot learning (FSL) problem, remains challenging, since traditional FSL research tends to disregard the intrinsic hierarchical nature of rare diseases and data uncertainty. To address these issues, we propose to conduct rare skin disease diagnosis in hyperbolic space, which facilitates implicit class hierarchical structures and precise uncertainty measurement due to pivotal geometrical properties. We propose a Hyperbolic Geometry-driven Robustness Enhancement (HGRE) framework specifically tailored for diagnosing rare skin diseases. The HGRE framework uses implicit hierarchical relation in the hyperbolic space to better represent the features of rare diseases. Moreover, the framework incorporates an Adversarial Proxy Construction (APC) module to address the problem of data uncertainty. Specifically, the APC module uses the distance to the hyperbolic space origin as an indicator of uncertainty to filter and construct adversarial proxies for each uncertain prototype to achieve adversarial robust training. Leveraging the two unique geometrical properties, our HGRE framework effectively addresses the limitations of insufficient hierarchical relation utilization and data uncertainty in FSL-based rare skin disease diagnosis. This enhancement of the model's robustness in training has been corroborated by extensive empirical validation on two skin lesion datasets, where HGRE's performance notably surpassed existing state-of-the-art FSL methods.

PMID:40030401 | DOI:10.1109/JBHI.2024.3500094

Proc Natl Acad Sci U S A. 2025 Mar 11;122(10):e2419992122. doi: 10.1073/pnas.2419992122. Epub 2025 Mar 3.

ABSTRACT

Variants with large effect contribute to congenital heart disease (CHD). To date, recessive genotypes (RGs) have commonly been implicated through anecdotal ascertainment of consanguineous families and candidate gene-based analysis; the recessive contribution to the broad range of CHD phenotypes has been limited. We analyzed whole exome sequences of 5,424 CHD probands. Rare damaging RGs were estimated to contribute to at least 2.2% of CHD, with greater enrichment among laterality phenotypes (5.4%) versus other subsets (1.4%). Among 108 curated human recessive CHD genes, there were 66 RGs, with 54 in 11 genes with >1 RG, 12 genes with 1 RG, and 85 genes with zero. RGs were more prevalent among offspring of consanguineous union (4.7%, 32/675) than among nonconsanguineous probands (0.7%, 34/4749). Founder variants in GDF1 and PLD1 accounted for 74% of the contribution of RGs among 410 Ashkenazi Jewish probands. We identified genome-wide significant enrichment of RGs in C1orf127, encoding a likely secreted protein expressed in embryonic mouse notochord and associated with laterality defects. Single-cell transcriptomes from gastrulation-stage mouse embryos revealed enrichment of RGs in genes highly expressed in the cardiomyocyte lineage, including contractility-related genes MYH6, UNC45B, MYO18B, and MYBPC3 in probands with left-sided CHD, consistent with abnormal contractile function contributing to these malformations. Genes with significant RG burden account for 1.3% of probands, more than half the inferred total. These results reveal the recessive contribution to CHD, and indicate that many genes remain to be discovered, with each likely accounting for a very small fraction of the total.

PMID:40030011 | DOI:10.1073/pnas.2419992122

Med Sci (Paris). 2025 Feb;41(2):173-179. doi: 10.1051/medsci/2025016. Epub 2025 Mar 3.

ABSTRACT

The aim of the MITOMICS project is to establish a clinical database of patients diagnosed with mitochondrial diseases, combined with a « multiomics » integrated approach in order to gain a better understanding of the molecular mechanisms underlying these diseases, and ultimately, to offer better patient care. The MITOMICS project thus contributes to the consolidation of a French "mitochondrial medicine", a notion that deserves to be examined. With the upcoming launch of the fourth national plan for rare diseases, it is an example of the study and management of rare and ultrarare diseases in France. This article traces the emergence of mitochondrial medicine since the early 1960s. It presents its main characteristics (genocentrism, strong techno-dependence), as well as its major technical and theoretical limitations, with a view to developing personalized mitochondrial medicine for the years to come.

PMID:40028956 | DOI:10.1051/medsci/2025016

Rev Mal Respir. 2025 Mar;42(3):148-152. doi: 10.1016/j.rmr.2025.02.009. Epub 2025 Feb 28.

ABSTRACT

Post-infectious bronchiolitis obliterans (PIBO) is a rare but severe pulmonary disease in children, often associated with adenovirus infection. Risk factors include male sex, hypoxemia, and mechanical ventilation. Diagnosis is based on clinical history, bronchial obstruction, and radiological abnormalities. PIBO is characterized by chronic inflammation leading to tissue remodeling and bronchiolar fibrosis. Airway epithelial lesions, potentially linked to viral infection, are considered key mechanisms of PIBO. In the absence of specific treatments, research efforts aim to better understand mechanisms of PIBO, identify biomarkers, and improve management strategies.

PMID:40023714 | DOI:10.1016/j.rmr.2025.02.009

Int J Gynecol Cancer. 2025 Mar;35(3):101669. doi: 10.1016/j.ijgc.2025.101669. Epub 2025 Jan 29.

ABSTRACT

More than half of all gynecological cancers are classified as rare (annual incidence <6 per 100,000), and present significant challenges in diagnosis, management, and research. Rare cancers collectively comprise more than 20% of new cancer diagnoses and exceed the burden of individual common cancers. Their rarity complicates evidence-based guideline development, clinical trial design, and drug access, and is exacerbated by variations in epidemiology, histology, and biological behavior. Key controversies include the need for centralized pathological reviews and harmonized diagnostic criteria. Recent World Health Organization classification updates, such as the redefinition of ovarian and fallopian tube cancers, illustrate the impact of evolving guidelines on epidemiology and patient management. Variations in the classification among pathologists and limited access to molecular diagnostics further hinder effective management. Multidisciplinary care in expert centers improves outcomes; however, significant geographic and resource disparities persist. National and international collaborations including European Reference Network for rare adult solid tumors, Gynecologic Cancer Intergroup, Gynecologic Oncology Group, Asia-Pacific Gynecologic Oncology Trials Group, and European Network for Gynaecological Oncology Trials have made strides in standardizing care and advancing research. Novel trial designs, such as basket and umbrella trials, alongside synthetic control arms, are essential for addressing the small sample sizes typical of rare tumors. Emerging consortia, such as International Ovarian Tumor Tissue Analysis Consortium and International Consortium for Low-grade Serous Ovarian Cancer, provide robust platforms for translational research and biomarker validation. However, challenges remain in fostering cross-border collaboration, streamlining regulatory pathways, and ensuring equitable access to trials and therapy. To optimize outcomes, a comprehensive approach that integrates centralized care, innovative trial designs, and international networks is imperative. This paradigm fosters the harmonization of care, accelerates translational research, and bridges the gap between scientific innovation and patient benefits.

PMID:40022843 | DOI:10.1016/j.ijgc.2025.101669

Clin Exp Rheumatol. 2025 Feb;43(2):309-315. doi: 10.55563/clinexprheumatol/dyjcsn. Epub 2025 Feb 26.

ABSTRACT

OBJECTIVES: This paper aims to provide insight into the challenges and opportunities of conducting an investigator-led, international, multicentre clinical trial for Inclusion Body Myositis (IBM), a rare inflammatory myopathy.

METHODS: An international, multicentre, randomised, controlled trial of a repurposed drug (sirolimus) was initiated based on promising results from a mono-centric pilot study. The progress of the trial was analysed to identify key challenges encountered and solutions developed.

RESULTS: This large, collaborative study has presented a mosaic of challenges and opportunities, many ubiquitous with investigator-led trials. Key challenges have included securing adequate funding, coordinating manufacture of placebo, negotiating international contracts, managing limited study budgets and delays linked to the COVID-19 pandemic. Alongside these challenges, the study team have found opportunities for creative and effective solutions, including the flexibility of building study databases, optimising digital data capture and harnessing patient involvement.

CONCLUSIONS: Instrumental to the progress of the trial has been the collaboration between site teams, patient partnership and adaptability.

PMID:40018747 | DOI:10.55563/clinexprheumatol/dyjcsn

NPJ Genom Med. 2025 Feb 27;10(1):13. doi: 10.1038/s41525-025-00474-8.

ABSTRACT

Advances in genomic technologies have revolutionized the diagnosis of rare genetic diseases, leading to the emergence of precision therapies. However, there remains significant effort ahead to ensure the promise of precision medicine translates to improved outcomes. Here, we discuss the challenges in advancing precision child health and highlight how international collaborations such as the International Precision Child Health Partnership, which embed research into clinical care, can maximize benefits for children globally.

PMID:40016282 | DOI:10.1038/s41525-025-00474-8

Turk J Ophthalmol. 2025 Feb 27;55(1):49-52. doi: 10.4274/tjo.galenos.2024.23934.

ABSTRACT

The purpose of this report is to present simultaneous bilateral penetrating keratoplasty (PK) in Acanthamoeba keratitis (AK). A 42-year-old male with keratoconus, wearing bilateral hybrid contact lenses, presented with pain in the left eye. He had a history of intrastromal corneal ring segment placement in the right and PK in the left eye. His best corrected visual acuity (BCVA) was 20/640 in the right eye and 20/2000 in the left. Slit-lamp examination revealed a ring-shaped infiltration on the left. Despite two months of broad-spectrum topical antibiotic therapy, microbiological examination of corneal scraping samples was repeated but revealed no evidence of microbial agents. In vivo confocal microscopy findings were not compatible with AK. During the follow-up, corneal infiltration and stromal melt were observed in the right eye. Corneal scraping samples from the right eye were sent for microbiological examination, but again no microbial agents were identified. Histopathological examination revealed spherical cysts consistent with AK. Corneal perforation developed in the right eye, while simultaneous wound dehiscence occurred in the left eye. Since the patient had a history of renal failure, simultaneous bilateral tectonic-therapeutic PK was performed to minimize the risks arising from general anesthesia. Postoperative BCVA was 20/50 in the right eye and 20/125 in the left eye at 6 months. Diagnostic tools can be misleading in eyes with altered anatomy. Careful examination and a timely decision to perform tectonic-therapeutic PK are vital in preventing devastating complications.

PMID:40013506 | DOI:10.4274/tjo.galenos.2024.23934

Orphanet J Rare Dis. 2025 Feb 26;20(1):88. doi: 10.1186/s13023-025-03581-y.

ABSTRACT

BACKGROUND: The mucopolysaccharidoses are a group of rare, inherited metabolic disorders. MPS II is a X-linked recessive disease, also known as Hunter syndrome. Clinical manifestations include upper and lower respiratory tract, and head and neck pathologies influencing quality of life, morbidity, and mortality. Medical and surgical intervention outcomes for MPS are reported inconsistently, creating a challenge when synthesising and contrasting evidence. This study set out to address the inconsistency in outcome measurement in this field. International recommendations for developing a core outcome set were adopted. Available data from qualitative studies and outcomes from a modified e-Delphi surveys were used to develop a list of candidate outcomes for consideration. Three consensus meetings with patients diagnosed with MPS II alongside their parents/carers were ran to help finalise a list of outcome domains.

RESULTS: Survival, airway obstruction, and quality of life were outcomes identified as important to always measure in all MPS II clinical trials and/or in clinical practice. Other outcomes for younger children included swallowing difficulties, cognitive development, ability to participate in education, and communication. The adolescent group included safety of chewing and swallowing, complications of anaesthesia, sleep quality and apnoea, nasal problems, and chronic otitis media. The adult group identified sleep apnoea, and hearing, as additional outcomes to measure.

CONCLUSIONS: A novel methodology for determining a core outcome set in rare diseases has been recommended. Both functional and quality of life outcomes were identified by the three age groups of individuals and/or their parents. Adoption of these sets of outcomes in future clinical trials and/or clinical practice will enable comparison of outcomes reported.

PMID:40011961 | DOI:10.1186/s13023-025-03581-y

Int J Equity Health. 2025 Feb 26;24(1):56. doi: 10.1186/s12939-025-02388-4.

ABSTRACT

BACKGROUND: Rare diseases, defined variably by global regions, collectively impact approximately 300 million individuals despite affecting small population segments individually. Historically there were no treatments developed for these conditions, leading to significant care challenges. Public interventions have incentivized treatment development, yet up to this day, many rare disease patients are deprived of timely diagnosis and treatment in comparison to patients with more common diseases. This study evaluates the challenges that rare disease patients and healthcare systems face in the Middle East and North Africa (MENA), seeking strategies to enhance treatment accessibility.

METHODS: We followed a three-step approach for the study. First, we searched scientific publications and grey literature for the global challenges faced by rare disease patients. Our search also collected information on orphan drug regulations implemented in different countries. Subsequently, we used the findings to conduct a survey to pharmaceutical company representatives across three countries in the region (The Kingdom of Saudi Arabia, Egypt, and the United Arab Emirates). The survey assessed the challenges facing rare disease patients in the MENA region and the policies that have been implemented to overcome these challenges. The survey was then followed by governmental expert interviews to validate the survey responses and provide recommendations to mitigate the challenges.

RESULTS: The literature and survey results revealed several challenges facing rare diseases, including lack of awareness, difficulty in acquiring marketing authorization and reimbursing orphan drugs. Validation meetings provided recommendations to mitigate such challenges in the selected countries. For instance, the collaboration between the Ministry of Health and pharmaceutical companies was recommended to improve rare diseases care. A separate registration process for orphan drugs with clear criteria and timelines was suggested. A differential cost-effectiveness threshold for orphan drugs was recommended. It was also recommended to establish a definition for rare diseases and to increase the utilization of managed entry agreements for orphan drugs.

CONCLUSIONS: Rare diseases present challenges in the MENA region and globally, requiring focused attention and innovative solutions. By implementing comprehensive strategies that consider both economic efficiency and fairness, healthcare systems can better serve rare disease patients and improve their quality of life.

PMID:40011905 | DOI:10.1186/s12939-025-02388-4

Sci Rep. 2025 Feb 26;15(1):6932. doi: 10.1038/s41598-025-90450-0.

ABSTRACT

Rare diseases (RDs) are a group of pathologies that individually affect less than 1 in 2000 people but collectively impact around 7% of the world's population. Most of them affect children, are chronic and progressive, and have no specific treatment. RD patients face diagnostic challenges, with an average diagnosis time of 5 years, multiple specialist visits, and invasive procedures. This 'diagnostic odyssey' can be detrimental to their health. Machine learning (ML) has the potential to improve healthcare by providing more personalized and accurate patient management, diagnoses, and in some cases, treatments. Leveraging the MIMIC-III database and additional medical notes from different sources such as in-house data, PubMed and chatGPT, we propose a labeled dataset for early RD detection in hospital settings. Applying various supervised ML methods, including logistic regression, decision trees, support vector machine (SVM), deep learning methods (LSTM and CNN), and Transformers (BERT), we validated the use of the proposed resource, achieving 92.7% F-measure and a 96% AUC using SVM. These findings highlight the potential of ML in redirecting RD patients towards more accurate diagnostic pathways and presents a corpus that can be used for future development and refinements.

PMID:40011510 | DOI:10.1038/s41598-025-90450-0

Orphanet J Rare Dis. 2025 Feb 25;20(1):86. doi: 10.1186/s13023-025-03595-6.

ABSTRACT

BACKGROUND: Rare diseases are conditions that have a low prevalence in the population and a high disease burden and are often chronic and progressive. International evidence concerning the experience of people and families living with rare diseases is scarce, leading to late and erroneous diagnoses, as well as non-specific treatments. This study explored the therapeutic trajectories of people and families living with rare diseases within Chile's public and private healthcare systems from the perspective of patients, caregivers, and medical teams, including the initial symptoms, first consultation, testing, diagnosis, treatment, and follow-up.

METHODS: A qualitative exploratory study was conducted through multiple case studies. Sixty participants were interviewed in person and/or virtually: patients (n = 16), caregivers (n = 22), healthcare workers (n = 20), and two patient organisation leaders. The material was analysed using thematic analysis. The project was approved by the Scientific Ethics Committee of Facultad de Medicina Clínica Alemana, Universidad del Desarrollo.

RESULTS: After similar initial symptoms and first consultation, three main types of trajectories were identified: (i) the path taken by those who reach a diagnosis for a disease that has specific treatment available; (ii) the journey of those who reach a diagnosis for their health condition, but their disease does not have a specific treatment available; and (iii) the trajectory of those who have not reached a diagnosis and receive symptomatic treatments for symptoms.

CONCLUSIONS: The therapeutic trajectories of patients with rare symptoms are similar in terms of initial symptoms and first consultation. However, their paths diverge at the diagnostic stage, with diverse experiences related to these journeys, largely based on having a diagnosis and whether there is a specific treatment. Rare conditions in Chile requires further attention and urgent action that considers those who live with them and their families.

PMID:40001237 | DOI:10.1186/s13023-025-03595-6

Lung Cancer. 2025 Mar;201:108449. doi: 10.1016/j.lungcan.2025.108449. Epub 2025 Feb 19.

ABSTRACT

BACKGROUND AND AIMS: NUT carcinoma (NC) is a sporadic, highly aggressive tumor that primarily affects children, adolescents, and young adults and is characterized by the presence of somatic NUTM1 rearrangements. This analysis by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) aims to fill the knowledge gap regarding the clinical characteristics of children with NC.

METHODS: A retrospective case series of NC-patients aged 0-18 years treated between 2011 and 2023 was conducted using the EXPeRT database. Relevant clinical characteristics, including treatment and outcome were recorded.

RESULTS: Twenty-seven patients with a median age of 13 years (range 7-18) were analyzed. Thirteen patients were initially misdiagnosed. Sixteen patients had thoracic and 11 extra-thoracic tumors, including three in the nasal/sinus region and two in the submandibular glands. Despite intense multimodal treatment, median event-free and overall survivals were 1.5 and 6.5 months, respectively.

CONCLUSIONS: Early diagnosis of NC by examination of the NUTM1 rearrangement in undifferentiated or poorly differentiated carcinomas is crucial in order to initiate specific and intensive therapy as quickly as possible. Similar to adult patients, only a minority of pediatric patients achieved prolonged survival. Therefore, the development of novel therapeutic strategies in future joint clinical trials is essential.

PMID:39999637 | DOI:10.1016/j.lungcan.2025.108449

BMC Cancer. 2025 Feb 25;25(1):352. doi: 10.1186/s12885-025-13782-0.

ABSTRACT

BACKGROUND: Patients with a rare cancer in rural, regional, and remote Australia experience heightened challenges in their illness journey, including significant psychosocial impacts. Although peer support has shown benefits for common cancer patients living in urban areas, these programs often do not reach underserved groups for instance those with a rare cancer, or those living in rural, regional or remote areas. This study aimed to explore the characteristics of peer support programs for patients with a rare cancer living in rural, regional or remote areas.

METHODS: Focus groups and interviews were conducted with 39 people with a rare cancer and 10 healthcare providers to explore key points for inclusion in a peer support service for people diagnosed with a rare cancer living in rural, regional or remote areas. Data were transcribed verbatim and analysed thematically, using Nvivo.

RESULTS: Participants described their peer support needs using the key terms who, what, how, where, and when. Participants advocated for a flexible, multicomponent intervention that could meet the varied and fluctuating needs of this group. Participants also noted challenges with the practical delivery of such a service, specifically, the risk of receiving misinformation, adverse emotional reactions, interpersonal challenges and implementation issues.

CONCLUSIONS: This study highlights the role of peer support in addressing unmet needs of patients with a rare cancer, particularly in rural areas, emphasising the importance of tailored, flexible, and multimodal interventions for the delivery of peer support that addresses diverse needs.

PMID:40001049 | DOI:10.1186/s12885-025-13782-0

Yonsei Med J. 2025 Mar;66(3):187-194. doi: 10.3349/ymj.2023.0628.

ABSTRACT

PURPOSE: Rare diseases occur in <50 per 100000 people and require lifelong management. However, essential epidemiological data on such diseases are lacking, and a consecutive monitoring system across time and regions remains to be established. Standardized digital phenotypes are required to leverage an international data network for research on rare endocrine diseases. We developed digital phenotypes for rare endocrine diseases using the observational medical outcome partnership common data model.

MATERIALS AND METHODS: Digital phenotypes of three rare endocrine diseases (medullary thyroid cancer, hypoparathyroidism, pheochromocytoma/paraganglioma) were validated across three databases that use different vocabularies: Severance Hospital's electronic health record from South Korea; IQVIA's United Kingdom (UK) database for general practitioners; and IQVIA's United States (US) hospital database for general hospitals. We estimated the performance of different digital phenotyping methods based on International Classification of Diseases (ICD)-10 in the UK and the US or systematized nomenclature of medicine clinical terms (SNOMED CT) in Korea.

RESULTS: The positive predictive value of digital phenotyping was higher using SNOMED CT-based phenotyping than ICD-10-based phenotyping for all three diseases in Korea (e.g., pheochromocytoma/paraganglioma: ICD-10, 58%-62%; SNOMED CT, 89%). Estimated incidence rates by digital phenotyping were as follows: medullary thyroid cancer, 0.34-2.07 (Korea), 0.13-0.30 (US); hypoparathyroidism, 0.40-1.20 (Korea), 0.59-1.01 (US), 0.00-1.78 (UK); and pheochromocytoma/paraganglioma, 0.95-1.67 (Korea), 0.35-0.77 (US), 0.00-0.49 (UK).

CONCLUSION: Our findings demonstrate the feasibility of developing digital phenotyping of rare endocrine diseases and highlight the importance of implementing SNOMED CT in routine clinical practice to provide granularity for research.

PMID:39999994 | DOI:10.3349/ymj.2023.0628

Cells. 2025 Feb 16;14(4):293. doi: 10.3390/cells14040293.

ABSTRACT

In vitro models serve as valuable tools for understanding the complex cellular and molecular interactions involved in granuloma formation, providing a controlled environment to explore the underlying mechanisms of their development and function. Various models have been developed to replicate granulomatous diseases, even though they may lack the sophistication needed to fully capture the variability present in clinical spectra and environmental influences. Traditional cultures of PBMCs have been widely used to generate granuloma models, enabling the study of aggregation responses to various stimuli. However, growing cells on a two-dimensional (2D) plastic surface as a monolayer can lead to altered cellular responses and the modulation of signaling pathways, which may not accurately represent in vivo conditions. In response to these limitations, the past decade has seen significant advancements in the development of three-dimensional (3D) in vitro models, which more effectively mimic in vivo conditions and provide better insights into cell-cell and cell-microenvironment interactions. Meanwhile, the use of in vivo animal models in biomedical research must adhere to the principle of the three Rs (replacement, reduction, and refinement) while ensuring that the models faithfully replicate human-specific processes. This review summarizes and compares the main models developed to investigate granulomas, focusing on their contribution to advancing our understanding of granuloma biology. We also discuss the strengths and limitations of each model, offering insights into their biological relevance and practical applications.

PMID:39996765 | DOI:10.3390/cells14040293

Neurol Genet. 2025 Feb 21;11(2):e200249. doi: 10.1212/NXG.0000000000200249. eCollection 2025 Apr.

ABSTRACT

OBJECTIVES: The primary objective of this paper was to present the establishment of the Spastic Paraplegia-Centers of Excellence Research Network (SP-CERN) aimed at promoting clinical trial readiness for hereditary spastic paraplegia (HSP). SP-CERN is unique in its approach to addressing the diagnostic and therapeutic challenges associated with HSP through a large-scale, collaborative effort.

METHODS: Participants with HSP are identified through multicenter collaborations across 11 institutions in the United States. SP-CERN systematically collects longitudinal clinical data, biospecimens, and wearable device data from patients. Data are stored in a centralized REDCap database, facilitating shared access for analysis. Patients are evaluated using standardized assessment tools for motor function, biomarkers, and digital outcome measures.

RESULTS: SP-CERN has established a biorepository, centralized data collection methods, and standardized clinical assessments. It is conducting natural history studies for all HSP subtypes, enabling the validation of biomarkers and development of gene-based therapies.

DISCUSSION: SP-CERN's collaborative approach bridges gaps in clinical care and research for HSP by improving diagnostic capabilities and promoting clinical trial readiness. This initiative represents a framework for rare disease research, accelerating the development of novel therapies and improving patient outcomes through standardized, multi-institutional collaboration.

PMID:39996129 | PMC:PMC11849523 | DOI:10.1212/NXG.0000000000200249

J Plast Surg Hand Surg. 2025 Feb 25;60:51-66. doi: 10.2340/jphs.v60.42953.

ABSTRACT

This qualitative systematic review aims to get a better understanding of what it means to live with a rare congenital craniofacial condition according to patients and their parents. Eight patient representatives provided input to this study. After a systematic search, 1,291 studies were screened and 32 qualitative and mixed methods articles (> 691 participants) were included. ENhancing Transparency in REporting the synthesis of Qualitative research (ENTREQ), Cochrane, and COnsolidated criteria for REporting Qualitative research (COREQ) checklists were used for reporting qualitative evidence synthesis and assessment of reporting of included studies. Studies predominantly included parents' perspectives and used mixed samples of diagnosis and sometimes combined the parent and patient perspectives. The results sections of the articles were analyzed inductively using Thematic Synthesis (i.e. line-by-line coding, generating descriptive and analytical themes). Five analytical themes were identified that describe experiences and perspectives: (1) Healthcare experiences, (2) Raising and Growing up, (3) Development of character, (4) Physical impact of the condition, and (5) Social experiences. Underlying themes illustrate that the different aspects throughout life are intertwined, that relationships in all different domains play an important role in shaping perspectives, and that experiences may change over time. Furthermore, it demonstrates that living with a craniofacial condition and undergoing treatment is multifaceted and that the perspectives of patients and parents may differ. In conclusion, well-being and quality of life of patients and their parents are dependent on many different aspects, and surgeons and other healthcare professionals should tailor their skills, expertise, and support to individual-specific needs besides medical indications and move beyond surgical excellence.

PMID:39995315 | DOI:10.2340/jphs.v60.42953

Am J Med Genet A. 2025 Feb 24:e63979. doi: 10.1002/ajmg.a.63979. Online ahead of print.

ABSTRACT

Transient abnormal myelopoiesis (TAM) is a transitory, myeloproliferative condition nearly exclusively present in infants with complete trisomy 21 (T21), or in its rare form, T21 mosaicism. We present here a case study of a neonate diagnosed with T21 mosaicism and TAM who did not exhibit the typical phenotypic features of down syndrome (DS), but displayed hematologic abnormalities, in addition to hepatosplenomegaly. Initial genetic testing suggested acute myeloid leukemia (AML) but subsequent evaluations were indicative of T21 mosaicism confined to the myeloid cell line, with negative results from lymphocytes cultured from a skin biopsy. A pathogenic GATA1 variant was found in the bone marrow in addition to three copies of RUNX1, associated with aberrant hematopoiesis in TAM. The infant responded to a brief course of chemotherapy and demonstrated normal growth and development at four years of age. In addition to this case, we identified 25 cases from the literature of mosaic T21 restricted to the myeloid cell line supporting normal development following treatment for TAM. As this case and the literature review demonstrate, T21 mosaicism apparently isolated to the bone marrow is unlikely to be associated with systemic or neurodevelopmental manifestations of DS.

PMID:39995092 | DOI:10.1002/ajmg.a.63979