Orphanet J Rare Dis. 2023 May 5;18(1):106. doi: 10.1186/s13023-023-02719-0.

ABSTRACT

Patient registries serve to overcome the research limitations inherent in the study of rare diseases, where patient numbers are typically small. Despite the value of real-world data collected through registries, adequate design and maintenance are integral to data quality. We aimed to describe an overview of the challenges in design, quality management, and maintenance of rare disease registries.A systematic search of English articles was conducted in PubMed, Ovid Medline/Embase, and Cochrane Library. Search terms included "rare diseases, patient registries, common data elements, quality, hospital information systems, and datasets". Inclusion criteria were any manuscript type focused upon rare disease patient registries describing design, quality monitoring or maintenance. Biobanks and drug surveillances were excluded.A total of 37 articles, published between 2001 and 2021, met the inclusion criteria. Patient registries covered a wide range of disease areas and covered multiple geographical locations, with a predisposition for Europe. Most articles were methodological reports and described the design and setup of a registry. Most registries recruited clinical patients (92%) with informed consent (81%) and protected the collected data (76%). Whilst the majority (57%) collected patient-reported outcome measures, only few (38%) consulted PAGs during the registry design process. Few reports described details regarding quality management (51%) and maintenance (46%).Rare disease patient registries are valuable for research and evaluation of clinical care, and an increasing number have emerged. However, registries need to be continuously evaluated for data quality and long-term sustainability to remain relevant for future use.

PMID:37147718 | PMC:PMC10163740 | DOI:10.1186/s13023-023-02719-0

BMC Med Inform Decis Mak. 2023 May 5;23(1):86. doi: 10.1186/s12911-023-02181-9.

ABSTRACT

BACKGROUND: Computational text phenotyping is the practice of identifying patients with certain disorders and traits from clinical notes. Rare diseases are challenging to be identified due to few cases available for machine learning and the need for data annotation from domain experts.

METHODS: We propose a method using ontologies and weak supervision, with recent pre-trained contextual representations from Bi-directional Transformers (e.g. BERT). The ontology-driven framework includes two steps: (i) Text-to-UMLS, extracting phenotypes by contextually linking mentions to concepts in Unified Medical Language System (UMLS), with a Named Entity Recognition and Linking (NER+L) tool, SemEHR, and weak supervision with customised rules and contextual mention representation; (ii) UMLS-to-ORDO, matching UMLS concepts to rare diseases in Orphanet Rare Disease Ontology (ORDO). The weakly supervised approach is proposed to learn a phenotype confirmation model to improve Text-to-UMLS linking, without annotated data from domain experts. We evaluated the approach on three clinical datasets, MIMIC-III discharge summaries, MIMIC-III radiology reports, and NHS Tayside brain imaging reports from two institutions in the US and the UK, with annotations.

RESULTS: The improvements in the precision were pronounced (by over 30% to 50% absolute score for Text-to-UMLS linking), with almost no loss of recall compared to the existing NER+L tool, SemEHR. Results on radiology reports from MIMIC-III and NHS Tayside were consistent with the discharge summaries. The overall pipeline processing clinical notes can extract rare disease cases, mostly uncaptured in structured data (manually assigned ICD codes).

CONCLUSION: The study provides empirical evidence for the task by applying a weakly supervised NLP pipeline on clinical notes. The proposed weak supervised deep learning approach requires no human annotation except for validation and testing, by leveraging ontologies, NER+L tools, and contextual representations. The study also demonstrates that Natural Language Processing (NLP) can complement traditional ICD-based approaches to better estimate rare diseases in clinical notes. We discuss the usefulness and limitations of the weak supervision approach and propose directions for future studies.

PMID:37147628 | PMC:PMC10162001 | DOI:10.1186/s12911-023-02181-9

Folia Med (Plovdiv). 2023 Apr 30;65(2):305-310. doi: 10.3897/folmed.65.e76245.

ABSTRACT

Autoimmune polyglandular syndromes (APS) are rare disorders characterized by the coexistence of endocrine and non-endocrine dysfunctions mediated by autoimmune mechanisms. Autoimmune polyglandular syndrome type 1 is defined as coexistence of chronic mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenal insufficiency. Addison's disease as the obligatory component is potentially life threatening.Herein, we demonstrate a case of a 44-year-old woman with APS-1 (hypoparathyroidism, adrenal insufficiency, hypergonadotropic hypogonadism) and SARS-CoV-2-induced adrenal crisis. The patient presented with the typical manifestations of hypotensive shock, electrolyte disturbances of hyponatremia and hyperkalemia, and hypoglycaemia.Our case report illustrates the increased risk of severe course of COVID-19 in APS-1 syndrome patients along with heightened exposure to medical complications. The case reinforced the significance of a timely diagnosis, appropriate treatment, and education of patients with such a rare condition like APS-1.

PMID:37144317 | DOI:10.3897/folmed.65.e76245

Mol Ther. 2023 May 3;31(5):1191-1192. doi: 10.1016/j.ymthe.2023.04.004.

NO ABSTRACT

PMID:37141855 | DOI:10.1016/j.ymthe.2023.04.004

Emerg Microbes Infect. 2023 Dec;12(1):2208685. doi: 10.1080/22221751.2023.2208685.

ABSTRACT

Dermatophytic pseudomycetoma is a rare invasive infection, involving both immunocompetent and immunocompromised individuals. Since the discovery of inherited immune disorders such as the impairment of CARD9 gene, extended dermatophyte infections are mostly ascribed to any of these host factors. This study is to present and explore the potential causes in a fatal dermatophytic pseudomycetoma patient. We present a chronic and deep pseudomycetoma caused by the common dermatophyte Microsporum canis which ultimately led to the death of the patient. Mycological examination, genetic studies and host immune responses against fungi were performed to explore the potential factors. The patient had decreased lymphocyte counts with significantly reduced CD4+ T cells, although all currently known genetic parameters proved to be normal. Through functional studies, we demonstrated that peripheral blood mononuclear cells from the patient showed severe impairment of adaptive cytokine production upon fungus-specific stimulation, whereas innate immune responses were partially defective. This is, to our knowledge, the first report of fatal dermatophytic pseudomycetoma in a patient with non-HIV CD4 lymphocytopenia, which highlights the importance of screening for immune deficiencies in patients with deep dermatophytosis.

PMID:37128909 | PMC:PMC10193896 | DOI:10.1080/22221751.2023.2208685

Am J Manag Care. 2023 Apr;29(4 Suppl):S51-S60. doi: 10.37765/ajmc.2023.89365.

ABSTRACT

Patients with rare diseases such as Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), a hematologic malignancy affecting approximately 1500 new patients per year, experience barriers to care involving both clinical and administrative factors. Optimal patient outcomes depend on timely identification, diagnosis of disease, and treatment initiation. For patients living with Ph+ ALL, the process can be delayed by limited treatment options approved by the US Food and Drug Administration and administrative hurdles that often delay treatment initiation. An overhaul of utilization management processes, such as the requirement for prior authorization (PA) for treatment, are needed to ensure patients have access to appropriate treatments in a timely manner. An AJMC Roundtable in November 2022 brought together a panel of payers and providers to discuss the challenges and shortcomings of current PA processes and to present ideas for potential solutions for improving them. Panelists at the roundtable discussed approaches including the use of guideline-concordant electronic PAs and other digital solutions, expedited approval pathways for use in specific conditions, use of real-world evidence in decision-making, issuance of PA "Gold Cards" to select providers, and a shift to value-based care agreements. Roundtable attendees agreed that, regardless of the strategy for PA-process improvement, there is a need for improved communication between providers and payers to ensure that the decision-making system meets the essential need for timely patient access to optimal care. This article reviews utilization management and guideline-concordant care through the lens of rare diseases and then presents solutions to utilization.

PMID:37129958 | DOI:10.37765/ajmc.2023.89365

AMIA Annu Symp Proc. 2023 Apr 29;2022:319-328. eCollection 2022.

ABSTRACT

Patient representation learning methods create rich representations of complex data and have potential to further advance the development of computational phenotypes (CP). Currently, these methods are either applied to small predefined concept sets or all available patient data, limiting the potential for novel discovery and reducing the explainability of the resulting representations. We report on an extensive, data-driven characterization of the utility of patient representation learning methods for the purpose of CP development or automatization. We conducted ablation studies to examine the impact of patient representations, built using data from different combinations of data types and sampling windows on rare disease classification. We demonstrated that the data type and sampling window directly impact classification and clustering performance, and these results differ by rare disease group. Our results, although preliminary, exemplify the importance of and need for data-driven characterization in patient representation-based CP development pipelines.

PMID:37128436 | PMC:PMC10148332

JAMA Neurol. 2023 May 1. doi: 10.1001/jamaneurol.2023.0473. Online ahead of print.

ABSTRACT

IMPORTANCE: Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy subtype and is often refractory to antiseizure medications. While most patients with MTLE do not have pathogenic germline genetic variants, the contribution of postzygotic (ie, somatic) variants in the brain is unknown.

OBJECTIVE: To test the association between pathogenic somatic variants in the hippocampus and MTLE.

DESIGN, SETTING, AND PARTICIPANTS: This case-control genetic association study analyzed the DNA derived from hippocampal tissue of neurosurgically treated patients with MTLE and age-matched and sex-matched neurotypical controls. Participants treated at level 4 epilepsy centers were enrolled from 1988 through 2019, and clinical data were collected retrospectively. Whole-exome and gene-panel sequencing (each genomic region sequenced more than 500 times on average) were used to identify candidate pathogenic somatic variants. A subset of novel variants was functionally evaluated using cellular and molecular assays. Patients with nonlesional and lesional (mesial temporal sclerosis, focal cortical dysplasia, and low-grade epilepsy-associated tumors) drug-resistant MTLE who underwent anterior medial temporal lobectomy were eligible. All patients with available frozen tissue and appropriate consents were included. Control brain tissue was obtained from neurotypical donors at brain banks. Data were analyzed from June 2020 to August 2022.

EXPOSURES: Drug-resistant MTLE.

MAIN OUTCOMES AND MEASURES: Presence and abundance of pathogenic somatic variants in the hippocampus vs the unaffected temporal neocortex.

RESULTS: Of 105 included patients with MTLE, 53 (50.5%) were female, and the median (IQR) age was 32 (26-44) years; of 30 neurotypical controls, 11 (36.7%) were female, and the median (IQR) age was 37 (18-53) years. Eleven pathogenic somatic variants enriched in the hippocampus relative to the unaffected temporal neocortex (median [IQR] variant allele frequency, 1.92 [1.5-2.7] vs 0.3 [0-0.9]; P = .01) were detected in patients with MTLE but not in controls. Ten of these variants were in PTPN11, SOS1, KRAS, BRAF, and NF1, all predicted to constitutively activate Ras/Raf/mitogen-activated protein kinase (MAPK) signaling. Immunohistochemical studies of variant-positive hippocampal tissue demonstrated increased Erk1/2 phosphorylation, indicative of Ras/Raf/MAPK activation, predominantly in glial cells. Molecular assays showed abnormal liquid-liquid phase separation for the PTPN11 variants as a possible dominant gain-of-function mechanism.

CONCLUSIONS AND RELEVANCE: Hippocampal somatic variants, particularly those activating Ras/Raf/MAPK signaling, may contribute to the pathogenesis of sporadic, drug-resistant MTLE. These findings may provide a novel genetic mechanism and highlight new therapeutic targets for this common indication for epilepsy surgery.

PMID:37126322 | DOI:10.1001/jamaneurol.2023.0473

Ann Nucl Cardiol. 2020;6(1):33-38. doi: 10.17996/anc.20-00128. Epub 2020 Aug 31.

ABSTRACT

Background: Triglyceride (TG) deposit cardiomyovasculopathy (TGCV) is a novel cardiovascular disorder and was recently encoded as an orphan disease in Europe (ORPHA code: 565612). Defective lipolysis results in TG accumulation in the myocardium and coronary arteries in TGCV. The myocardial washout rate (WR) of iodine-123-β-methyl iodophenyl-pentadecanoic acid (BMIPP) is an essential indicator to evaluate myocardial lipolysis in vivo. TGCV is classified into primary and idiopathic type with and without PNPLA2 mutation, respectively. Here, we present the clinical correlation perspectives of TGCV patients in Chiba, Japan, to increase the awareness of this orphan disease and facilitate its diagnosis. Methods: We enrolled 234 patients who underwent BMIPP scintigraphy between September 2015 and July 2019. The diagnosis of TGCV was made based on the criteria we reported previously. Blood smear tests were performed for TGCV classification. The distributions of TGCV in each comorbidity were investigated. Results: In total, 104 patients were diagnosed with definitive idiopathic TGCV (I-TGCV). They had various comorbid conditions, including heart failure with reduced ejection fraction and multivessel coronary artery disease requiring revascularization. Moreover, the serum TG levels in I-TGCV patients were not high, and there was no correlation between serum TG level and BMIPP WR (n=205, p-value=0.31), supporting the pathophysiological hypothesis of TGCV. Conclusion: I-TGCV patients showed multiple coexistence of coronary artery disease, heart failure of unknown etiology, or diabetes mellitus. For patients with such clinical characteristics, BMIPP scintigraphy and calculation of WR should be considered proactively for the diagnosis of TGCV.

PMID:37123494 | PMC:PMC10133925 | DOI:10.17996/anc.20-00128

J Transl Med. 2023 Apr 30;21(1):292. doi: 10.1186/s12967-023-04152-0.

ABSTRACT

The recent paper by Kariampuzha et al. describes an exciting application of artificial intelligence to rare disease epidemiology. The authors' AI model appears to offer a major leap over Orphanet, the resource which is often a "first stop" for basic epidemiological data on rare diseases. To ensure appropriate use of this exciting tool, it is important to consider its strengths and weaknesses in context. The tool currently incorporates only PubMed abstracts, so key information located in the full text of articles is absent. Such missing information may include incidence and prevalence values, as well as important elements of study design and context. Additionally, results from the public version of the tool differ from those described in the original article, including obsolete values for prevalence and the use of non-prevalence studies in place of those listed in the article. At present, it would be appropriate to utilize the AI tool much like Orphanet: a helpful "first stop" which should be manually checked for completeness and accuracy. Users should understand the benefits of this exciting technology, and that it is not yet a panacea for the challenges of analyzing rare disease epidemiology.

PMID:37122037 | DOI:10.1186/s12967-023-04152-0

Orphanet J Rare Dis. 2023 Apr 29;18(1):99. doi: 10.1186/s13023-023-02703-8.

ABSTRACT

If esophageal papilloma (EP) is a rare condition, esophageal papillomatosis (EPS) is a distinct rarity. To date, only 53 well documented cases have been described in English literature. However, the number of reports on EPS significantly increased to over 40 cases during the past 20 years. Perhaps, this is due to the broad use of endoscopy and related research achievements. Most of the cases are individual and it seems that there are no associations between them. And up to now no guidelines can be followed. To further understand this exceedingly rare disease, we had a comprehensive review of the epidemiology, etiology, clinical manifestations, pathogenesis, treatment, and clinical course of EPS.

PMID:37120568 | DOI:10.1186/s13023-023-02703-8

Orphanet J Rare Dis. 2023 Apr 28;18(1):97. doi: 10.1186/s13023-023-02672-y.

ABSTRACT

BACKGROUND: Rare diseases are a particular field of public health that is characterized by scattered, often insufficient knowledge and infrastructure. The scarcity of specialized knowledge often forces clinicians and patients to an incomplete picture of the diseases and their associated risks. Effective person-centred networks appear promising for solving such real world and life-defining problems by purposely sourcing expert knowledge that is geographically-dispersed. The design and implementation of the RARE-e-CONNECT network technology is described. The project was funded to create collaborative spaces for the development of international partnerships in Cyprus' healthcare, promoting the dissemination of expert knowledge on rare diseases while saving resources through teleconsultation. Parameters that matter for patients, providers and policy-makers through the RARE-e-CONNECT experience were evaluated through a participatory mixed-method approach, consisting of (1) a needs assessment survey with 27 patients/families and 26 healthcare professionals at the two referral hospitals for the diagnosis and management of rare diseases in Cyprus; (2) interviews with 40 patients, families and patient representatives, as well as 37 clinicians and laboratory scientists, including national ERN coordinators/members; (3) activity metrics from 210 healthcare professionals and 251 patients/families/patient representatives who participated on the platform at the time of the research.

RESULTS: Our results indicate usage and intention by both healthcare professionals and patients/families to openly provide decentralized specialized information for raising suspicion amongst clinicians to facilitate the necessary referrals, as well as peer to peer psychosocial support to help cope with the everyday challenges of living with the disease. User behavior was largely affected by the prevailing social norm favoring individual practice, as well as missing policies for telemedicine and shared care. This article discusses how telehealth is inextricably linked to social, cultural, organizational, technological and policy factors affecting uptake.

CONCLUSIONS: We argue that collective intelligence tools need to be formally considered and work hand in hand with national and European policies/regulatory frameworks to promote proactiveness amongst the healthcare community with regard to the timely diagnosis of rare diseases and the facilitation of patients' pathway to specialists. Collaborative channels between countries need to be established to source collective intelligence on complex cases and save resources through teleconsultation/telementoring.

PMID:37118739 | PMC:PMC10142407 | DOI:10.1186/s13023-023-02672-y

Viruses. 2023 Apr 18;15(4):995. doi: 10.3390/v15040995.

ABSTRACT

Mpox (previously known as monkeypox) is an infectious viral illness caused by the mpox virus (MPXV), an orthopoxvirus that belongs to the family Poxviridae. The symptoms of mpox in humans are similar to those of smallpox, although the mortality rate is lower. In recent years, the concern over a potential global pandemic has increased due to reports of mpox spreading across Africa and other parts of the world. Prior to this discovery, mpox was a rare zoonotic disease restricted to endemic regions of Western and Central Africa. The sudden emergence of MPXV cases in multiple regions has raised concerns about its natural evolution. This review aims to provide an overview of previously available information about MPXV, including its genome, morphology, hosts and reservoirs, and virus-host interaction and immunology, as well as to perform phylogenetic analysis on available MPXV genomes, with an emphasis on the evolution of the genome in humans as new cases emerge.

PMID:37112975 | PMC:PMC10142743 | DOI:10.3390/v15040995

Int J Mol Sci. 2023 Apr 21;24(8):7666. doi: 10.3390/ijms24087666.

ABSTRACT

Kimura's disease (KD) is a rare lymphoproliferative fibroinflammatory disorder that commonly affects the subcutaneous tissue and lymph nodes of the head and neck. The condition is a reactive process involving T helper type 2 cytokines. Concurrent malignancies have not been described. Differential diagnosis with lymphoma can be challenging without tissue biopsy. Here, we present the first reported case of coexisting KD and eosinophilic nodular sclerosis Hodgkin lymphoma of the right cervical lymphatics in a 72-year-old Taiwanese man.

PMID:37108825 | PMC:PMC10146151 | DOI:10.3390/ijms24087666

Int J Mol Sci. 2023 Apr 14;24(8):7275. doi: 10.3390/ijms24087275.

ABSTRACT

The expression "rare disease" describes a group of diseases whose individual prevalence is low (between 3.9 and 6.6 in 10,000 subjects depending on the country) but which in total affect up to the 3-6% of the worldwide population [...].

PMID:37108436 | PMC:PMC10139002 | DOI:10.3390/ijms24087275

Ann Med Surg (Lond). 2023 Apr 10;85(4):1231-1234. doi: 10.1097/MS9.0000000000000473. eCollection 2023 Apr.

ABSTRACT

Alagille syndrome has been described as a multisystemic clinical spectrum caused by an autosomal dominant genetic disorder. Although it is estimated that there is 1 case per 100 000 live births, the prognosis for survival and quality of life for these patients is varied but tends to be negative. In Colombia, this condition is considered an orphan disease with difficult management due to the lack of specialized centers that have all the medical specialties and subspecialties. Some reports state that no more than 30 cases have been published in this country.

MATERIALS AND METHODS: The authors report a case of a male baby who, at 8 days old, he was taken to the general practitioner's outpatient clinic for persistent jaundice. At 3 months of age, he was reviewed by the pediatric gastroenterology department, which requested liver and biliary tract scintigraphy, showing atresia of the biliary tract, hepatomegaly, and the absence of a gallbladder.

RESULTS: Liver transplantation is the definitive solution. However, in low- and middle-income countries, where there are no well-established organ transplantation programs, the prognosis for these patients is presumed to be worse.

CONCLUSION: Alagille syndrome is a rare disease that requires an accurate and early diagnosis and timely multidisciplinary management to reduce the impact of multisystemic complications. It is necessary to advance in transplant programs in low- and middle-income countries, to provide a solution to cases where there are no other therapeutic alternatives, and to contribute to the quality of life of the affected patient.

PMID:37113962 | PMC:PMC10129178 | DOI:10.1097/MS9.0000000000000473

Medicina (Kaunas). 2023 Apr 11;59(4):745. doi: 10.3390/medicina59040745.

ABSTRACT

Background and objectives: Bullous pemphigoid (BP), the most common subepidermal autoimmune skin blistering disease (AIBD) has an estimated annual incidence of 2.4 to 42.8 new cases per million in different populations, designating it an orphan disease. Characterized by disruption of the skin barrier combined with therapy-induced immunosuppression, BP could pose a risk for skin and soft tissue infections (SSTI). Necrotizing fasciitis (NF) is a rare necrotizing skin and soft tissue infection, with a prevalence of 0.40 cases per 100,000 to 15.5 cases per 100,000 population, often associated with immunosuppression. Low incidences of NF and BP classify them both as rare diseases, possibly contributing to the false inability of making a significant correlation between the two. Here, we present a systematic review of the existing literature related to the ways these two diseases correlate. Materials and methods: This systematic review was conducted according to the PRISMA guidelines. The literature review was conducted using PubMed (MEDLINE), Google Scholar, and SCOPUS databases. The primary outcome was prevalence of NF in BP patients, while the secondary outcome was prevalence and mortality of SSTI in BP patients. Due to the scarcity of data, case reports were also included. Results: A total of 13 studies were included, six case reports of BP complicated by NF with six retrospective studies and one randomized multicenter trial of SSTIs in BP patients. Conclusions: Loss of skin integrity, immunosuppressive therapy, and comorbidities commonly related to BP patients are risk factors for necrotizing fasciitis. Evidence of their significant correlation is emerging, and further studies are deemed necessary for the development of BP-specific diagnostic and treatment protocols.

PMID:37109703 | DOI:10.3390/medicina59040745

Genes (Basel). 2023 Mar 23;14(4):779. doi: 10.3390/genes14040779.

ABSTRACT

BACKGROUND: Children and adolescents with early-onset psychosis (EOP) have more rare genetic variants than individuals with adult-onset forms of the illness, implying that fewer EOP participants are needed for genetic discovery. The Schizophrenia Exome Sequencing Meta-analysis (SCHEMA) study predicted that 10 genes with ultra-rare variation were linked to adult-onset schizophrenia. We hypothesized that rare variants predicted "High" and "Moderate" by the Variant Effect Predictor Algorithm (abbreviated as VEPHMI) in these 10 genes would be enriched in our EOP cohort.

METHODS: We compared rare VEPHMI variants in individuals with EOP (N = 34) with race- and sex-matched controls (N = 34) using the sequence kernel association test (SKAT).

RESULTS: GRIN2A variants were significantly increased in the EOP cohort (p = 0.004), with seven individuals (20% of the EOP cohort) carrying a rare VEPHMI variant. The EOP cohort was then compared to three additional control cohorts. GRIN2A variants were significantly increased in the EOP cohort for two of the additional control sets (p = 0.02 and p = 0.02), and trending towards significance for the third (p = 0.06).

CONCLUSION: Despite a small sample size, GRIN2A VEPHMI variant burden was increased in a cohort of individuals with EOP in comparison to controls. GRIN2A variants have been associated with a range of neuropsychiatric disorders including adult-onset psychotic spectrum disorder and childhood-onset schizophrenia. This study supports the role of GRIN2A in EOP and emphasizes its role in neuropsychiatric disorders.

PMID:37107537 | DOI:10.3390/genes14040779

Sci Rep. 2023 Apr 27;13(1):6869. doi: 10.1038/s41598-023-33374-x.

ABSTRACT

Up to 40% of rare disorders (RD) present facial dysmorphologies, and visual assessment is commonly used for clinical diagnosis. Quantitative approaches are more objective, but mostly rely on European descent populations, disregarding diverse population ancestry. Here, we assessed the facial phenotypes of Down (DS), Morquio (MS), Noonan (NS) and Neurofibromatosis type 1 (NF1) syndromes in a Latino-American population, recording the coordinates of 18 landmarks in 2D images from 79 controls and 51 patients. We quantified facial differences using Euclidean Distance Matrix Analysis, and assessed the diagnostic accuracy of Face2Gene, an automatic deep-learning algorithm. Individuals diagnosed with DS and MS presented severe phenotypes, with 58.2% and 65.4% of significantly different facial traits. The phenotype was milder in NS (47.7%) and non-significant in NF1 (11.4%). Each syndrome presented a characteristic dysmorphology pattern, supporting the diagnostic potential of facial biomarkers. However, population-specific traits were detected in the Colombian population. Diagnostic accuracy was 100% in DS, moderate in NS (66.7%) but lower in comparison to a European population (100%), and below 10% in MS and NF1. Moreover, admixed individuals showed lower facial gestalt similarities. Our results underscore that incorporating populations with Amerindian, African and European ancestry is crucial to improve diagnostic methods of rare disorders.

PMID:37106005 | PMC:PMC10140286 | DOI:10.1038/s41598-023-33374-x

Orphanet J Rare Dis. 2023 Apr 25;18(1):93. doi: 10.1186/s13023-023-02698-2.

ABSTRACT

PURPOSE: The transition process from paediatric/adolescent to adult medical care settings is of utmost importance for the future health of adolescents with chronic diseases and poses even more difficulties in the context of rare diseases (RDs). Paediatric care teams are challenged to deliver adolescent-appropriate information and structures. Here we present a structured transition pathway which is patient-focused and adoptable for different RDs.

METHODS: The transition pathway for adolescents 16 years and older was developed and implemented as part of a multi-centre study in 10 university hospitals in Germany. Key elements of the pathway included: assessment of patients' disease-related knowledge and needs, training/educational and counselling sessions, a structured epicrisis and a transfer appointment jointly with the paediatric and adult specialist. Specific care coordinators from the participating university hospitals were in charge of organization and coordination of the transition process.

RESULTS: Of a total of 292 patients, 286 completed the pathway. Deficits in disease-specific knowledge were present in more than 90% of participants. A need for genetic or socio-legal counselling was indicated by > 60%. A mean of 2.1 training sessions per patient were provided over a period of almost 1 year, followed by the transfer to adult care in 267 cases. Twelve patients remained in paediatric care as no adult health care specialist could be identified. Targeted training and counselling resulted in improved disease-specific knowledge and contributed to empowering of patients.

CONCLUSION: The described transition pathway succeeds to improve health literacy in adolescents with RDs and can be implemented by paediatric care teams in any RD specialty. Patient empowerment was mainly achieved by individualized training and counselling.

PMID:37098531 | PMC:PMC10131406 | DOI:10.1186/s13023-023-02698-2