Rare最新文献

{"title":"Venture philanthropy in rare disease therapy","authors":"JA Levine","doi":"10.1016/j.rare.2025.100099","DOIUrl":"10.1016/j.rare.2025.100099","url":null,"abstract":"<div><h3>Purpose</h3><div>Rare diseases affect ∼350 million people globally, yet 94 % of those affected lack effective treatments due to funding gaps and high R&amp;D costs. Traditional investment models often fail due to a combination of small patient populations and limited commercial return. This study investigates venture philanthropy (VP) as an alternative model that merges philanthropic goals with venture capital strategies to accelerate the development of rare disease therapies. The research explores (i) VP’s impact on financial sustainability, translational efficiency, and clinical advancement; (ii) the structural, operational, and strategic factors influencing VP-funded biotech outcomes; and (iii) the utility of the DACMAR (Disruption, Adoption, Collaboration, Management, Adaptability, and Resource Optimization) framework in optimizing VP investments.</div></div><div><h3>Methods</h3><div>A mixed-methods design was employed. Data sources included (i) stakeholder focus groups to identify key issues in rare disease VP; (ii) semi-structured interviews with 15 stakeholders, including funders, advocates, and biotechnology company executives; (iii) a systematic analysis of 26 VP organizations using 30 investment criteria; and (iv) the application of DACMAR to assess best practices. A thematic analysis was applied to the qualitative data to evaluate the alignment between organizational practices and therapeutic advancement.</div></div><div><h3>Findings</h3><div>Organizations fulfilling multiple DACMAR domains demonstrated improved outcomes, including clinical trial progression and regulatory designations. Disruptive investment in antisense and gene therapies, early regulatory engagement (Adopt), and formal collaborations (Collaborate) accelerated trials. Additionally, milestone-based funding (Manage), adaptive decision-making (Adapt), and long-term infrastructure planning (Resource Optimization) enhanced organizational resilience. Persistent barriers included regulatory delays, limited low- and middle- income country engagement, and insufficient data systems.</div></div><div><h3>Conclusion</h3><div>VP is a viable mechanism for addressing unmet needs in rare disease therapeutics. DACMAR offers a practical, replicable framework for de-risking investments and scaling impact. This work’s findings can inform funders, biotech leaders, and policymakers committed to advancing patient-centered innovation.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100099"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary ciliary dyskinesia: A review","authors":"Shally Awasthi ,&nbsp;Shambhavi Mishra","doi":"10.1016/j.rare.2025.100098","DOIUrl":"10.1016/j.rare.2025.100098","url":null,"abstract":"<div><h3>Context</h3><div>Primary ciliary dyskinesia (PCD) is a rare genetic disease characterized by impaired mucociliary clearance in the respiratory tract due to abnormal ciliary motility. The disease is often diagnosed late with bronchiectasis. This review explores the clinical and genetic correlates of PCD and advances in its management.</div></div><div><h3>Evidence acquisition</h3><div>Electronic databases such as PubMed, Scopus, Web of Science, and Google Scholar were searched using the keywords \"ciliary motility disorders,\" \"situs inversus,\" \"recurrent rhinitis,\" and \"bronchiectasis.\" Reference lists of the retrieved studies, including original articles, reviews, case reports, and case series from the last 30 years, were also reviewed.</div></div><div><h3>Results</h3><div>Nasal nitric oxide (nNO) is a screening tool, but some genetic variants show discrepancies with nNO measurements. Future diagnostics will focus on genotype determination and its association with phenotype, ciliary structure, and function.</div><div>Exhaled breath condensate is also a potential diagnostic tool. New treatments include azithromycin maintenance therapy (BESTCILIA-trial). Gene therapy and mRNA therapy are emerging as promising approaches.</div></div><div><h3>Conclusion</h3><div>PCD diagnosis and treatment are often delayed due to its presumed rarity.However, the increasing discovery of new genetic variants worldwide indicates it is underestimated. Unexplained neonatal respiratory distress, early onset recurrent rhinosinusitis, recurrent otitis media, and reduced fertility are subtle indicators of PCD.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100098"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A first large study of whole-exome sequencing (WES) in 489 patients with suspected rare genetic disorders at a tertiary centre in Malaysia","authors":"Lip Hen Moey ,&nbsp;Go Hun Seo ,&nbsp;Boon Eu Cheah ,&nbsp;Wee Teik Keng ,&nbsp;Hane Lee ,&nbsp;Gaik Siew Ch’ng","doi":"10.1016/j.rare.2025.100102","DOIUrl":"10.1016/j.rare.2025.100102","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Rare genetic disorders occur at a rate of 40–82 per 1000 live births worldwide. Identifying the molecular cause of rare genetic disorders is beneficial because it allows early diagnosis, facilitates treatment planning and provision of accurate genetic counselling. In Malaysia, it is estimated that 1.5–2 million (4–6 %) people from a population of 34 million suffer from rare disorders, most of which are genetic in origin. Tests offered to patients referred to genetic clinics in Malaysia include conventional karyotyping, Fragile X testing, metabolic screening and/or single gene testing. Chromosomal microarray analysis (CMA) and gene-panel testing are not routinely offered due to lack of laboratory resources. Hence, the majority of rare disease patients remain undiagnosed for many years. Whole exome sequencing (WES) is a comprehensive test that can detect not only many of the same large deletions and duplications as CMA, but also detect other genetic variants that are detected by gene panels. Therefore, WES is cost effective and fast becoming a routine clinical test worldwide for patients suspected to have rare genetic disorders.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;div&gt;This is a retrospective study conducted at a single genetic centre in Malaysia. From August 2020 to December 2021, proband-only WES was offered to patients suspected of having a genetic disorder after clinical evaluation by a clinical geneticist. WES was performed at a single reference laboratory in South Korea. Patient demographic information, clinical features, genetic test results were collected from the case notes for analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 489 patients underwent WES. Eighty-three percent (407/489) were paediatric patients. The majority of the patients presented with neurodevelopmental symptoms. WES identified the underlying genetic cause in 50 % (243/489, 95 % confidence interval (CI): 45 %-54 %) of the patients. A reanalysis of WES data, with or without additional phenotypic information, yielded a diagnosis for 17 of the 228 WES-negative patients, resulting in the final diagnostic yield of 53 % (260/489, 95 % CI: 49 %-58 %). Nine of these patients received dual molecular genetic diagnosis&lt;strong&gt;.&lt;/strong&gt; Twenty one patients were diagnosed with a copy-number-variant (CNV). The inheritance patterns of the diagnosed disorders were 64 % autosomal dominant (171/268), 24 % autosomal recessive (65/268) and 12 % X-linked (32/268). 82 % (401/489) of the patients opted to receive secondary finding results, of which 5.5 % (22/401, 95 % CI: 3.6 %-8.2 %) had P/LP variants in genes associated with cardiovascular disorders (64 %, 14/22) or cancer (27 %, 6/22).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This study demonstrated the high efficiency of WES in confirming rare genetic diagnoses among patients referred to a genetic clinic in Malaysia. Identifying resources to fund this test would be of utmost importance to achieve the aim o","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100102"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of living with Ehlers-Danlos Syndrome on health-related quality of life: A systematic review following the 2017 international EDS classification","authors":"Joanna Foster ,&nbsp;Elaine Walklet ,&nbsp;Danielle Stephens-Lewis","doi":"10.1016/j.rare.2025.100107","DOIUrl":"10.1016/j.rare.2025.100107","url":null,"abstract":"<div><h3>Objective</h3><div>The Ehlers-Danlos Syndromes (EDS) are a group of multi-systemic, chronic conditions with complex symptomology. This systematic review aimed to synthesise what is known about the impact of EDS on Health-Related Quality of Life (HRQoL), and associated moderating factors, following a change in diagnostic criteria.</div></div><div><h3>Methods</h3><div>Fifteen databases, grey literature and reference lists were systematically searched. A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and guidelines for narrative synthesis. Findings were grouped according to outcomes, moderating factors, and measurement instrument. A further synthesis aligned outcomes with domains of HRQoL. Risk of bias was addressed using the Effective Public Health Practice Project assessment tool.</div></div><div><h3>Results</h3><div>Eight quantitative studies met eligibility criteria. Findings indicate substantial impact due to symptoms and functional status. However, how HRQoL is measured potentially introduces bias such that other factors are overlooked.</div></div><div><h3>Conclusion</h3><div>This review suggests key aspects of how HRQoL is experienced remain underexplored and underreported. Issues of methodological rigour raise further concerns around the usefulness of study findings. Further research is required to clarify how aspects of HRQoL are prioritised and experienced and how they can best be measured, to improve management of this debilitating condition.</div><div><strong>PROSPERO registration number</strong> CRD42022318979</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100107"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Rare Hackathon: An extracurricular educational event to promote rare disease awareness among students in medicine and life sciences","authors":"Begum Utz ,&nbsp;Emine Eylul Taskin ,&nbsp;Ayca Yigit ,&nbsp;Emre Ozzeybek ,&nbsp;Kutay Bulut ,&nbsp;Ece Sonmezler ,&nbsp;Aykut Kuruoglu ,&nbsp;Aliye Kubra Unal ,&nbsp;Noor Fatima ,&nbsp;Pinar Gencpinar ,&nbsp;Duygu Sag ,&nbsp;Yavuz Oktay ,&nbsp;Nur Arslan ,&nbsp;Ayse Semra Hiz ,&nbsp;Nese Atabey ,&nbsp;Ugur Ozbek","doi":"10.1016/j.rare.2025.100106","DOIUrl":"10.1016/j.rare.2025.100106","url":null,"abstract":"<div><div>Globally, millions of individuals are affected by rare diseases (RDs), yet there remains a significant gap in medical and life sciences education regarding RDs. This gap frequently leads to delays and challenges for patients in clinical settings and negatively impacts RD research. To address this, the EU-funded RareBoost project team organized the ‘Rare Hackathon’, as part of 2025 Rare Disease Day activities. The hackathon was designed as an educational event for undergraduate and graduate students, in which the student teams were asked to ‘solve’ two complex rare disease scenarios. Unlike similar hackathons, this event did not involve a patient cohort reanalysis. The teams developed diagnostic solutions, investigated genotype-phenotype correlations, and suggested experimental disease models to study gene-disease relationships. In a public session, the teams presented their solutions to a jury and received awards to further boost their scientific education. A post-event survey revealed that most students had limited prior exposure to RDs. The students reported that the hackathon helped them gain a better understanding of RD research, diagnosis, and challenges. Many students also expressed interest in working in the RD field in the future. Furthermore, students had valuable suggestions such as extending the event duration, incorporating training sessions, and including treatment design aspects. The Rare Hackathon successfully demonstrated how an extracurricular activity can raise awareness of RDs among medical and life sciences students. Incorporating similar events during students’ academic training can help close the gap in RD education, and as a result, improve outcomes for individuals living with rare conditions.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100106"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstracts of the 2023 UDNI Conference","authors":"","doi":"10.1016/j.rare.2024.100055","DOIUrl":"10.1016/j.rare.2024.100055","url":null,"abstract":"","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of social deprivation as a modifier of phenotypic divergence in PTEN Hamartoma Tumor Syndrome","authors":"Parker L. Bussies ,&nbsp;David Bruckman ,&nbsp;Lamis Yehia ,&nbsp;Takae Mizukami ,&nbsp;Karen Hurley ,&nbsp;Jarrod Dalton ,&nbsp;Charis Eng","doi":"10.1016/j.rare.2024.100053","DOIUrl":"10.1016/j.rare.2024.100053","url":null,"abstract":"<div><div>Pathogenic mutations in phosphatase and tensin homolog (<em>PTEN</em>), a tumor suppressor gene, leads to the development of <em>PTEN</em> Hamartoma Tumor Syndrome (PHTS). Patients carry significantly increased risks for cancer and neurodevelopmental disorders such as autism spectrum disorder (ASD). The factors which modify <em>PTEN</em> function and drive PHTS phenotype remain unknown. Social determinants of health are increasingly being identified as important regulators of disease pathogenesis. Here, we conduct a retrospective cross-sectional study to evaluate the association between social deprivation, as measured by area deprivation index (ADI), and neurodevelopmental versus cancer phenotypes in patients with PHTS. Our findings suggest ADI alone is not associated with PHTS phenotype, and that its divergence is likely multifactorial in nature. More broadly, our study highlights the importance of integrating environmental pressures with genetic risk modification in the study of complex human disease.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143133067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare homozygous CNPY3 variant causing autosomal recessive developmental and epileptic encephalopathy 60: A case report","authors":"Nohela Rehman ,&nbsp;Zohra Hasan Ali ,&nbsp;Mahrukh Nasir ,&nbsp;Salman Kirmani","doi":"10.1016/j.rare.2025.100081","DOIUrl":"10.1016/j.rare.2025.100081","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Epilepsy is one of the most common neurological disorders, affecting around 50 million people globally. Developmental and epileptic encephalopathy 60 (DEE60) is an autosomal recessive disorder caused by mutations in the Canopy FGF signaling regulator 3 (&lt;em&gt;CNPY3&lt;/em&gt;) gene. Symptoms start in infancy and include developmental delay, seizures, and myoclonus, with EEGs showing hypsarrhythmia indicative of West syndrome. &lt;em&gt;CNPY3&lt;/em&gt; is crucial for Toll-like receptor chaperoning and can potentially cause neuronal circuit imbalances. This report examines the first reported instance of DEE60 in Pakistan with a missense mutation in the &lt;em&gt;CNPY3&lt;/em&gt; gene, aiming to advance the current literature on &lt;em&gt;CNPY3&lt;/em&gt; and bring attention to a rare condition that currently only has symptomatic treatment. Only five cases have been reported globally.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methodology&lt;/h3&gt;&lt;div&gt;Informed consent was obtained from the patient’s parents for the publication of this study and patient confidentiality has been maintained such that no data in the submission can reveal the patient's identity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Case presentation&lt;/h3&gt;&lt;div&gt;A 5-month-old male, born of consanguineous parents, presented to the Aga Khan University Hospital with severe seizures, a history of global developmental delay and a family history of seizures. The patient had his first seizure at 3 months and was started on antiseizure medications. He was born full-term via caesarean section, requiring oxygen support postnatally due to delayed cry and cyanosis. He exhibited delayed developmental milestones, low interaction levels, unresponsiveness to loud sounds and no smiling since birth. Systemic examinations were normal, but MRI and EEG findings suggested West Syndrome, DEE, and inborn errors of metabolism (IEM). Whole exome sequencing (WES) revealed a homozygous likely pathogenic variant in the &lt;em&gt;CNPY3&lt;/em&gt; gene (NM_006586.5) c.275 C&gt;T (p.Ser92Leu, rs556172653), confirming DEE60. At follow-up, the patient experienced increased seizure frequency, intermittent fever, recurrent chest infections and decreased muscle tone. Management included anti-seizure medications, benzodiazepines, anticonvulsants, neurobiotin, folic acid, vitamin B and ACTH. The parents were counselled about DEE60, prenatal testing, and a 25 % occurrence of recessive disorders. There is currently no gene therapy for this condition.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Comment&lt;/h3&gt;&lt;div&gt;The variant reported in dataebases is predicted to be deleterious, consistent with the phenotype observed in our patient. ClinVar records 34 &lt;em&gt;CNPY3&lt;/em&gt; variants with 20 variants of uncertain significance. This highlights the need for further research to understand &lt;em&gt;CNPY3&lt;/em&gt;-associated phenotypes and its role in neuronal activity. Improved newborn and genetic testing access in Pakistan is essential for timely diagnosis and management, given the high costs of foreign labs and the risk of undiagnosed cases.&lt;/d","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100081"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The BeWayAPDS project: Designing the best way to optimize management of activated PI3Kδ syndrome (APDS) in Spain from the perspective of key stakeholders","authors":"María Elena Seoane-Reula ,&nbsp;Carmen Garrido-Colino ,&nbsp;Inmaculada Mediavilla ,&nbsp;Laia Alsina ,&nbsp;Miguel García ,&nbsp;Jose Luis Poveda ,&nbsp;Carlos Mur ,&nbsp;Sandra Flores ,&nbsp;Carmen Alerany ,&nbsp;María Ángeles Escobar Palazón ,&nbsp;Carlos Jiménez ,&nbsp;Macarena Sierra ,&nbsp;Kirsten H. Herrmann ,&nbsp;Alicia Gil","doi":"10.1016/j.rare.2025.100071","DOIUrl":"10.1016/j.rare.2025.100071","url":null,"abstract":"<div><h3>Background</h3><div>Rare diseases represent a challenge for healthcare systems due to lack of awareness, complexity in management and the limited published evidence available. Activated phosphoinositide 3-kinase delta syndrome (APDS) involves different healthcare specialists from diagnosis to long-term follow-up. Being an ultra-rare chronic complex disorder categorized within inborn errors of immunity (IEI) without clinical guidelines or disease modifying treatments, several challenges arise in patient management. This study aims to elucidate current diagnosis and management processes, identify challenges and opportunities and design a patient pathway directed at improving patient outcomes.</div></div><div><h3>Methods</h3><div>A literature review was performed to develop a questionnaire to obtain evidence through individual interviews with a multistakeholder panel of experts. A patient pathway was proposed by the experts, including main challenges encountered through management of APDS and proposing potential practical solutions. Challenges were prioritised, identifying those with the highest potential to improve patient management. The proposed patient pathway and the prioritisation of challenges and solutions were then discussed in a reflective group discussion.</div></div><div><h3>Results</h3><div>A patient pathway was designed and validated including diagnosis, short- and long-term follow-up. Challenges identified impact different steps of the pathway, affecting optimal disease diagnosis, management and outcomes. The solutions proposed included the constitution of IEI multidisciplinary teams, early diagnosis in the symptomatic phase, development of an APDS treatment guideline/algorithm, implementation of artificial intelligence (AI) tools to support diagnosis, training in IEI in Primary Care (PC) centres and reinforcement of patient experience and perspective in decision-making.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening, diagnostic, and monitoring approaches of Bardet-Biedl Syndrome: A scoping review","authors":"Letícia Nunes Campos ,&nbsp;Ivo Valentin Rudzinski ,&nbsp;Gabriela Oriana Pintos ,&nbsp;Santino Curto ,&nbsp;Santiago Miguel Maximowicz ,&nbsp;Ayla Gerk ,&nbsp;Israel Dávila Rivera ,&nbsp;Federico Fernandez Zelcer ,&nbsp;Carlos Stegmann ,&nbsp;Carina Francisca Argüelles ,&nbsp;Jorgelina Stegmann","doi":"10.1016/j.rare.2025.100092","DOIUrl":"10.1016/j.rare.2025.100092","url":null,"abstract":"<div><h3>Introduction</h3><div>Bardet-Biedl Syndrome (BBS) is a rare, autosomal recessive, multisystemic ciliopathy. Providing care for BBS presents challenges due to limited data. This scoping review aimed to characterize evidence for screening, diagnosing, and monitoring BBS.</div></div><div><h3>Methods</h3><div>We searched ten databases for articles published in English and Spanish between January 2017 and October 2023. We selected human-based research that utilized methods to assess BBS, including experimental, quasi-experimental, observational studies, reviews, and guidelines. Screening and data extraction were performed by two independent reviewers, with a third reviewer involved to resolve disagreements. We employed descriptive statistical analyses and qualitative synthesis.</div></div><div><h3>Results</h3><div>We included 113 articles from 32 countries, mainly constituting case reports (n = 45, 39.8 %). Prenatal ultrasound was the most frequently reported screening method (n = 15, 13.3 %) for detecting early BBS indicators. Clinical manifestations were crucial in raising suspicion of BBS, with nearly all references adopting the diagnostic criteria by Forsythe and Beales. Central obesity, retinal rod-cone dystrophy, and postaxial polydactyly were the most frequently documented manifestations. Genetic testing was also essential to diagnosing BBS, with techniques such as next-generation sequencing confirming up to 80 % of cases. Articles reported variants in a total of 41 genes, including those encoding BBSome proteins, chaperones, and components of the IFT. Furthermore, we identified the most frequently assessed clinical features during patient follow-up. Notably, we observed that few articles reported complementary exams to evaluate BBS's clinical manifestations.</div></div><div><h3>Conclusions</h3><div>Our results provide valuable insights for healthcare professionals, facilitating evidence-based, ongoing care for patients with BBS.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100092"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}