Orphanet Journal of Rare Diseases最新文献

{"title":"Arthrogryposis Multiplex Congenita (AMC) and counselling before and during pregnancy: a questionnaire study.","authors":"Arda Arduç, Julia Slootbeek, Johanna I P de Vries, Maria B Tan-Sindhunata, Femke Stoelinga, Bonita Sawatzky, Isabel Filges, Ingeborg H Linskens","doi":"10.1186/s13023-025-03913-y","DOIUrl":"10.1186/s13023-025-03913-y","url":null,"abstract":"<p><strong>Background: </strong>Pre-pregnancy counselling in women with Arthrogryposis Multiplex Congenita (AMC) is not implemented as standard care. Prior surveys revealed that the majority of adults with AMC live independently with or without support, are working, and engage in social actifities. Although many of them underwent pregnancies, literature is scarce concerning women with AMC and pregnancies. This study enquires information of women with AMC and their preferences to optimize counselling and guidance concerning aspects related to (pre-)pregnancy, childbirth and parenthood. Women with AMC, being members of an international AMC patient support group or Canadian register, were invited anonymously via newsletter in mail or announcement on social media.</p><p><strong>Results: </strong>A total of 53 women with confirmed AMC participated in this questionnaire study. Pregnancies were reported in 64.2% (34/53) of the women and 26 women had multiple pregnancies and delivered in total 45 children. A third (15/45) of the children were born vaginally and the remaining per caesarean section. None of the children had AMC. Four women reported on complications during application of local analgesia in labour and in 3 while positioning on the operating table. Of the 47 women who answered this question, 95.7% (45/47) expressed a wish for standard pre-pregnancy counselling. As optimal circumstances they prefer counselling at or above 18 years of age, by a gynaecologist, at the outpatient clinic and for those with a relationship together with their partner. The importance of multidisciplinary team of physicians was emphasized as well as information from peer support groups and websites. Women expressed concerns about lack of knowledge on AMC in healthcare workers, discontinuity in care and attitude towards treatment and acknowledged the importance of this study.</p><p><strong>Conclusions: </strong>This study provides unique insights from women with AMC regarding pregnancy and parenthood. Participants emphasized the importance of tailored care. Their preferences strongly advocate for implementing pre-pregnancy counselling from the age of 18, ideally by a multidisciplinary team including a gynecologist. Incorporating these perspectives is essential to improve reproductive care.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"378"},"PeriodicalIF":3.5,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety findings from the phase 1/2 MOSAIC study of miransertib for patients with PIK3CA-related overgrowth spectrum or Proteus syndrome.","authors":"Whitney Eng, Ionela Iacobas, Jonathan Perkins, Giuseppe Zampino, Chiara Leoni, Paola Sabrina Buonuomo, Alessandra Simonetti, Himanshu Goel, Michael Briones, Mo Huang, Gregory Goldmacher, Danny Liaw, Adrienne Hammill","doi":"10.1186/s13023-025-03831-z","DOIUrl":"10.1186/s13023-025-03831-z","url":null,"abstract":"<p><strong>Background: </strong>PIK3CA-related overgrowth spectrum (PROS) and Proteus syndrome are associated with mosaic tissue overgrowth of varying severity that commonly presents in childhood. The multicenter, open-label, phase 1/2 MOSAIC study (NCT03094832) was designed to evaluate the clinical efficacy and safety of the selective pan-AKT inhibitor miransertib for participants with PROS or Proteus syndrome.</p><p><strong>Methods: </strong>Participants ≥ 2 years of age with PROS with documented somatic PIK3CA mutations or Proteus syndrome with documented somatic AKT1 mutations were enrolled to receive oral miransertib at a starting dose of 15 mg/m² every day for the first 3 cycles (1 cycle = 28 days) and miransertib 25 mg/m² every day thereafter, provided no clinically significant drug-related toxicities were observed. The initial primary objective of the study was to assess clinical response to miransertib. Due to study design and data collection limitations, evaluating efficacy was no longer considered feasible and the primary objective was updated in 2021 to evaluate the safety and tolerability of miransertib.</p><p><strong>Results: </strong>Between May 16, 2017 and January 25, 2021, 49 participants were enrolled and received ≥ 1 dose of study drug, comprising the safety analysis population. Forty-five participants had a diagnosis of PROS and four had a diagnosis of Proteus syndrome. The median (range) age at enrollment was 7 years (2-41). Median (range) duration of treatment was 20.5 months (9.9-45.6). A total of 23 (46.9%) participants had a drug-related adverse event, most commonly decreased neutrophil count (n = 6, 12.2%), increased blood insulin (n = 5, 10.2%), and stomatitis (n = 5, 10.2%). One (2.0%) participant experienced a grade 3 drug-related adverse event (deep vein thrombosis). No drug-related adverse events led to early study discontinuation or death. Laboratory assessment values remained generally stable throughout the study.</p><p><strong>Conclusion: </strong>Miransertib was safe and tolerable in participants with a confirmed diagnosis of PROS or Proteus syndrome. Future investigations are needed to determine whether patients receive measurable clinical benefit from miransertib.</p><p><strong>Trial registration: </strong>NCT03094832 registered Mar 28, 2017, https://clinicaltrials.gov/ct2/show/NCT03094832 .</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"375"},"PeriodicalIF":3.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype-phenotype variations in PURA syndrome: Asian and non-Asian perspectives from a systematic review.","authors":"Shu-Ning Liu, Ching-Shiang Chi, Hsiu-Fen Lee, Chi-Ren Tsai, Yao-Lun Yang, Pei-Yu Wu","doi":"10.1186/s13023-025-03908-9","DOIUrl":"10.1186/s13023-025-03908-9","url":null,"abstract":"<p><strong>Background: </strong>The focus of this study was a comparison of the phenotypical and genotypical differences in PURA syndrome among Asian and non-Asian patients. A retrospective cohort study was performed in a single medical center from January 2014 to May 2025 on patients carrying causative genes for PURA syndrome. A systematic search in PubMed, MEDLINE, Web of Science, and Embase covering the period from January 2014 to May 2025 was conducted. Individuals with PURA syndrome were collected and categorized into Asian and non-Asian groups for analysis. Clinical characteristics, imaging findings, and developmental outcomes were compared between the two groups using Chi-squared or Fisher's exact tests, with a p < 0.05 considered statistically significant.</p><p><strong>Results: </strong>Of 200 individuals enrolled, 44 were Asian and 156 were non-Asian. 80% or more of individuals with PURA syndrome in both groups shared common clinical features of hypotonia and feeding difficulties during the neonatal period. In terms of neurologic symptoms, there were significantly higher rates of pathological startle response (p < 0.01), and lower rates of epilepsy (p < 0.01) and movement disorders (p = 0.035) among Asian populations. For extra-neurologic symptoms, Asian populations showed a higher incidence of cardiac (p = 0.013) and urogenital abnormalities (p < 0.01), with statistical significance. A single patient in the cohort study exhibited second-degree atrioventricular block, which required pacemaker placement. Highly heterogeneous variants were identified with 106 causative variants in 200 individuals, including a novel causative variant, c.42_57del (p.Leu15fs), from our cohort. All individuals with PURA syndrome displayed evident psychomotor impairment during follow-up.</p><p><strong>Conclusions: </strong>PURA syndrome exhibits high phenotypic and genotypic heterogeneity. Increased pathological startle response, reduced epilepsy and movement disorders, and higher rates of cardiac and urogenital abnormalities were observed in the Asian group. Cardiac conduction disorder may prove fatal without timely intervention.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"376"},"PeriodicalIF":3.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introducing a revised version of the Kumamoto scale as an easy-to-use clinical tool for monitoring multisystemic changes in hereditary transthyretin amyloidosis.","authors":"Jonas Wixner, Björn Pilebro, Tale N Wien, Per Eldhagen, Henning Mölgaard, Björn Hedström, Astrid J Terkelsen","doi":"10.1186/s13023-025-03915-w","DOIUrl":"10.1186/s13023-025-03915-w","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin (ATTRv) amyloidosis is a rare but life-threatening multisystemic disease. Multiple disease-modifying treatments are now available and standardised instruments for early detection and disease monitoring are essential. Still, validated and easy-to-use tools for clinical follow-up are scarce.</p><p><strong>Methods: </strong>The Kumamoto scale was first described in 1997 as a method for systematically evaluating patients with ATTRv amyloidosis and has been used in clinical trials since. A panel of amyloidosis experts from Sweden, Denmark, and Norway discussed the strengths and limitations of the Kumamoto scale at the Nordic Amyloidosis Day at Arlanda in 2023, and it was decided to revise and improve the scale that has been used in routine clinical monitoring of patients in Sweden since 2020. Our aim is to introduce the revised version of the Kumamoto scale as a useful clinical monitoring tool.</p><p><strong>Results: </strong>Minor adjustments were applied to make the scale more sensitive and precise. Bedside instruments for sensory examination were defined as well as the sensory and motor levels. Constipation was added as a sign of autonomic dysfunction. The subtotal and total scores remain unchanged.</p><p><strong>Conclusions: </strong>We believe that the revised Kumamoto scale is a reliable and easy-to-use clinical tool for monitoring ATTRv amyloidosis.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"377"},"PeriodicalIF":3.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The burden of illness in Prader-Willi syndrome: a systematic literature review.","authors":"Dairine Dempsey, Maria Hall, Ben Lanning, Ben Barron-Millar, Michael Huang, Neil Cowen, Mitch Nagao, Raj Gandhi, Anish Bhatnagar","doi":"10.1186/s13023-025-03787-0","DOIUrl":"10.1186/s13023-025-03787-0","url":null,"abstract":"<p><strong>Background: </strong>Prader-Willi syndrome (PWS) is a rare, genetic neurobehavioral and metabolic disorder marked by hyperphagia, behavioral challenges, and significant comorbidities, requiring a multidisciplinary approach for effective management. This systematic review aimed to comprehensively evaluate the burden of disease associated with PWS, focusing on mortality, healthcare resource utilization, economic burden, and quality of life.</p><p><strong>Methods: </strong>The literature search, conducted on August 13, 2024, included the MEDLINE, Embase, and Cochrane Library databases, as well as conference proceedings. Original studies published since 2014 were selected based on relevance to PWS patient burden, covering mortality, humanistic and economic impacts. Data from the selected studies were extracted, and currency conversions were standardized.</p><p><strong>Results: </strong>For the topics of mortality, humanistic burden and economic burden, a total of 11 studies, 95 studies, and 33 studies were included, respectively. Individuals with PWS faced significantly reduced life expectancy compared to the general population, with leading causes of death including respiratory failure, consequences of uncontrolled hyperphagia, and cardiovascular complications. Hyperphagia contributed substantially to the disease burden, necessitating constant food security measures to prevent life-threatening complications. Primary caregivers, predominantly parents of individuals with PWS, experienced significant emotional and psychological strain. The time-intensive responsibilities of implementing food security measures heavily impacted their daily lives, social and family dynamics, as well as their financial health. Quality of life for patients was less frequently reported but markedly impaired, driven by physical health challenges, behavioral issues, and social isolation. Wider family dynamics were also often impacted, with siblings reporting increased psychosocial stress and feelings of neglect. The direct costs of managing PWS, including frequent hospitalizations and specialized care, were consistently reported to exceed those of matched controls without PWS, highlighting the substantial economic burden associated with the condition.</p><p><strong>Conclusion: </strong>This systematic literature review highlights the profound burden of PWS on patients, caregivers, payers of care, and healthcare systems. Complications of PWS reduce life expectancy, impair quality of life, and impose considerable financial strain. The findings underscore an urgent need for comprehensive support and innovative treatments that address the complex manifestations and consequences of PWS, particularly hyperphagia, to improve outcomes for patients and their families.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"374"},"PeriodicalIF":3.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophy.","authors":"Takanori Onuki, Makiko Tajika, Yohei Sugiyama, Masaru Shimura, Keiko Ichimoto, Toju Tanaka, Hiromi Nyuzuki, Motomichi Kosuga, Ohsuke Migita, Tetsuya Ito, Hideo Sasai, Ryosuke Bo, Junpei Hamada, Takashi Hamazaki, Norio Sakai, Takahito Inoue, Kimitoshi Nakamura, Torayuki Okuyama, Kei Murayama","doi":"10.1186/s13023-025-03848-4","DOIUrl":"10.1186/s13023-025-03848-4","url":null,"abstract":"<p><strong>Background: </strong>Recently, Newborn screening (NBS) has been expanded worldwide to include lysosomal storage diseases (LSDs) and adrenoleukodystrophy (ALD) due to the importance of early diagnosis and early treatment. In Japan, NBS for LSDs, termed expanded NBS, was first implemented in Kumamoto prefecture in 2006 as pilot study. NBS for ALD was subsequently introduced in Aichi prefecture and Gifu prefecture in 2021. Expanded NBS for LSDs and ALD has become more widespread in Japan. In light of this current situation, we considered it is necessary to clarify the usefulness of expanded NBS, prevalence of each disease, challenges encountered. Therefore, we reported the current implementation status of expanded NBS in Japan.</p><p><strong>Method: </strong>A survey was conducted among physicians responsible for expanded NBS in each target region Japan. The target regions were those that implemented NBS for LSDs and/or ALD for more than one year. The survey items included: the entity conducting expanded NBS, the facilities conducting the tests, the target areas, medical institutions for close examination such as detailed biochemical analysis and/or genetic sequencing, and treatments, types of target diseases, fee for NBS, sample collection methods, testing method, and quantitative data on expanded NBS, retesting, and diagnoses in each area.</p><p><strong>Results: </strong>Responses were received from nine regions and an organization (CReARID). The total number of 733,838 newborns were screening, with 101 diagnoses: 75 cases of Fabry disease, 10 of mucopolysaccharidosis (MPS) II, 8 of Pompe disease, 5 of Gaucher disease, 2 of MPS I, 1 of ALD, respectively) were diagnosed. More cases were diagnosed with the target disease than the estimated prevalence. In contrast, the positive predictive value was low and false-positive rates was elevated, particularly for PD, MPS II, and ALD, have been attributed to pseudodeficiency alleles and methodological differences. Moreover, variant of unknown significance (VUS) in the ABCD1 gene was detected in many of the patients with suspected ALD.</p><p><strong>Conclusion: </strong>In Japan, Expanded NBS for LSDs and ALD has become more widespread. Since its implementation, some patients have been diagnosed and received treatment. However, challenges such as pseudodeficiency, indications, testing methods, and VUS that require improvement.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"373"},"PeriodicalIF":3.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First 100 patients receiving long-acting growth hormone therapy: real-world evaluation from INSIGHTS-GHT registry.","authors":"Joachim Woelfle, I Kreitschmann-Andermahr, C J Strasburger, D B Pittrow, C Pausch, D Schnabel","doi":"10.1186/s13023-025-03898-8","DOIUrl":"10.1186/s13023-025-03898-8","url":null,"abstract":"<p><p>The development of long-acting growth hormone (LAGH) formulations offers a promising approach to reduce injection frequency and to improve adherence in growth hormone deficiency (GHD) treatment. INSIGHTS-GHT is the first product-independent registry to document the real-world use of recombinant human (rh) growth hormone (GH) replacement therapy within the labelling. Following the market launch of three LAGH products in Germany (lonapegsomatropin, somapacitan, and somatrogon) we aimed to provide early real-world evidence on their use in order to obtain an initial picture on patient selection and physician preferences outside of clinical trials.We report in this interim analysis on 70 pediatric patients from 15 centers across Germany as well as 31 adult patients from 6 German centers under LAGH treatment. The majority of the pediatric patients (76%) were male, with a mean age at LAGH initiation of 9.2 years. About half of the pediatric patients (54%) were switch patients transitioning from daily GH therapy. Notably, 82% of patients received a LAGH starting dose below the manufacturer's recommendation, with a median dose of 92% of the recommended level. In the group of adult patients, 65% were male, with a mean age of 38.2 years at LAGH initiation. In pediatric patients, before start of GH therapy, mean IGF-I (SDS) was - 2.1 ± 1.1 SDS, mean IGFBP-3 (SDS) was - 2.0 ± 1.5 SDS.All adult patients switched from daily GH therapy. More than half (55%) received the LAGH starting dose according to the manufacturer's recommendation, while 41% began with a lower-than-recommended dose. Our findings provide early insights into LAGH therapy adoption and highlight the need for continued follow-up to evaluate long-term efficacy, adherence, and safety in real-world settings.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"372"},"PeriodicalIF":3.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"It's like nursing a butterfly-so delicate, difficult, and unpredictable\" - challenges of nurses in caring for patients with epidermolysis bullosa: a qualitative study.","authors":"Parivash Karimi, Moloud Radfar, Yaser Moradi","doi":"10.1186/s13023-025-03925-8","DOIUrl":"10.1186/s13023-025-03925-8","url":null,"abstract":"<p><strong>Background: </strong>Patients with Epidermolysis Bullosa (EB) face extensive and complex challenges, and nurses play a decisive role in providing care for them and educating their families. However, the multifaceted nature of EB care introduces significant challenges for nurses.</p><p><strong>Objective: </strong>This study aimed to explore the challenges nurses face in caring for patients with EB.</p><p><strong>Methods: </strong>This is a qualitative study conducted from August to December 2024. Semi-structured, in-depth, face-to-face interviews were conducted with 15 nurses who provided care to patients with EB in Urmia, Northwest Iran. Data were analyzed using the conventional content analysis approach proposed by Graneheim and Lundman (2004).</p><p><strong>Results: </strong>Data analysis revealed three main categories of challenges faced by nurses in caring for patients with EB: \"Problematic Parental Reactions\" which includes harmful parental demands, difficult initial encounters, and parental detachment; \"Care Avoidance\" encompassing arduous routine care and the psycho-erosive nature of care; and \"The Forgotten Illness\" characterized by limited organizational support and insufficient organizational knowledge enhancement.</p><p><strong>Conclusion: </strong>Caring for EB patients presents numerous challenges for nurses, including Problematic Parental Reactions, care avoidance, and the broader context of a forgotten illness. Parental demands, difficult initial encounters, and parental detachment complicate the care, while the demanding and psycho-erosive nature of daily tasks exacerbates nurse fatigue. Furthermore, organizational neglect-stemming from inadequate resources and insufficient training-intensifies these difficulties. These findings highlight the need for targeted training programs and systemic support to address the unique difficulties inherent in caring for patients with EB.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"371"},"PeriodicalIF":3.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silver-Russell syndrome: phenotype features and oral health status.","authors":"Paula Piekoszewska-Ziętek, Aneta Witt-Porczyk, Krystyna Chrzanowska, Małgorzata Zadurska, Dorota Olczak Kowalczyk","doi":"10.1186/s13023-025-03886-y","DOIUrl":"10.1186/s13023-025-03886-y","url":null,"abstract":"<p><strong>Background: </strong>Silver-Russell Syndrome is a rare malformation syndrome with a variable clinical and genetic presentation. Its incidence is estimated at 1:70.000-1:100.000 births. Since the diagnosis of Silver-Russell syndrome is based primarily on the identification of clinical features, studies assessing the craniofacial/dental changes present in this group of patients are important. The aim of the study was to evaluate phenotype features and oral health status in patients with Silver-Russell syndrome.</p><p><strong>Results: </strong>In the extraoral examination, patients with SRS were found to have a triangular facial shape, facial asymmetry, low-set, protruding ears, narrow lips and downward-facing mouth angles. In intraoral examination, reduced tongue dimensions, cleft palate and gothic palate were observed. There were no statistically significant differences in Plaque Index values between the groups. Gingival Index values were significantly higher in the Silver-Russell syndrome. The prevalence of caries was also higher in the group of subjects with Silver-Russell syndrome.</p><p><strong>Conclusions: </strong>Patients with Silver-Russell syndrome present themselves with features that affect oral health. Prompt orthodontic and dental intervention in children with SRS can help normalize oral function and facial appearance.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"370"},"PeriodicalIF":3.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo applications and toxicities of AAV-based gene therapies in rare diseases.","authors":"Qian Zhao, Huifang Peng, Yujin Ma, Huijun Yuan, Hongwei Jiang","doi":"10.1186/s13023-025-03893-z","DOIUrl":"10.1186/s13023-025-03893-z","url":null,"abstract":"<p><p>Adeno-associated virus (AAV), renowned for its exceptionally low pathogenicity and significant efficacy in clinical gene therapy, has emerged as a leading delivery vector in the field of gene therapy. AAV can achieve stable gene expression in various tissues, which has made it a promising treatment for genetic disorders. To date, eight AAV-based gene therapies have been approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA). This review summarizes clinical trials of AAV gene therapies for rare diseases, including ophthalmic diseases, nervous system disorders, hematological diseases, neuromuscular diseases, lysosomal storage diseases. We also explore potential side effects and toxicities associated with AAV therapies. Our objective is to provide valuable insights for researchers and clinicians working on AAV-based therapies, helping improve the safety and effectiveness of these treatments.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"368"},"PeriodicalIF":3.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}