G Ital Cardiol (Rome). 2024 Feb;25(2):98-105. doi: 10.1714/4187.41758.

ABSTRACT

Left ventricular non-compaction (LVNC) is a myocardial disease characterized by a two-layered structure typically seen at the apical and lateral left portions of the ventricular myocardium, distal to the papillary muscles. While considered a rare disease, its prevalence in children is increasing due to the increased awareness of this condition and improved resolution of imaging techniques. The etiology is heterogeneous, ranging from inherited conditions to acquired diseases. Although many patients are asymptomatic, some patients may experience adverse events, including heart failure, arrhythmias, or thromboembolic events. Several echocardiographic or cardiac magnetic resonance imaging diagnostic criteria have been proposed for diagnosing LVNC. However, their application in children is significantly limited. This review aims to describe the clinical and genetic characteristics of children with LVNC and discuss the role of the proposed diagnostic criteria.

PMID:38270365 | DOI:10.1714/4187.41758

Dis Model Mech. 2024 Jun 1;17(6):dmm050672. doi: 10.1242/dmm.050672. Epub 2024 Jan 25.

NO ABSTRACT

PMID:38270284 | PMC:PMC10846506 | DOI:10.1242/dmm.050672

Stud Health Technol Inform. 2024 Jan 25;310:1151-1155. doi: 10.3233/SHTI231145.

ABSTRACT

SelEe is a German citizen science project aiming to develop a smartphone app for a patient-managed record. The goal is to study rare diseases with the support of interested citizens and people affected by rare diseases. We established a core research team, including professional researchers (leading the project) and citizens. Citizens have the opportunity to discuss the progress, make suggestions regarding the app's design and data entry and contribute to the dissemination of the project. To gather feedback and experiences from the core research team, we performed an online questionnaire regarding the topics "influence and communication", "improvements and learning effect", and "satisfaction". Finally, 9 citizens of the core research team participated. The results show that the citizens are very satisfied with the design of the app, their participation opportunities and the communication in the project.

PMID:38269995 | DOI:10.3233/SHTI231145

Stud Health Technol Inform. 2024 Jan 25;310:94-98. doi: 10.3233/SHTI230934.

ABSTRACT

Drug development in rare diseases is challenging due to the limited availability of subjects with the diseases and recruiting from a small patient population. The high cost and low success rate of clinical trials motivate deliberate analysis of existing clinical trials to understand status of clinical development of orphan drugs and discover new insight for new trial. In this project, we aim to develop a user centered Rare disease based Clinical Trial Knowledge Graph (RCTKG) to integrate publicly available clinical trial data with rare diseases from the Genetic and Rare Disease (GARD) program in a semantic and standardized form for public use. To better serve and represent the interests of rare disease users, user stories were defined for three types of users, patients, healthcare providers and informaticians, to guide the RCTKG design in supporting the GARD program at NCATS/NIH and the broad clinical/research community in rare diseases.

PMID:38269772 | DOI:10.3233/SHTI230934

BMJ Case Rep. 2024 Jan 23;17(1):e257130. doi: 10.1136/bcr-2023-257130.

ABSTRACT

Malakoplakia is a rare granulomatous disease. Its aetiology is unclear but possible theories include infection with microorganisms (especially Escherichia coli), immunosuppression and impaired lysosomal function. It has been commonly documented to affect the genitourinary tract but can affect any organ, with the gastrointestinal system being the next most affected. We present a woman in her 70s, with a 2-week history of right-sided abdominal pain, 13 years following her renal transplant. She was admitted for treatment of an E. coli bacteraemia. CT scan had shown a caecal pole mass, highly suspicious for malignancy. It was surgically resected, and histology revealed findings of malakoplakia within the colon. Surgical intervention was combined with a prolonged course of antibiotics for successful treatment. We highlight the ability of malakoplakia to mimic malignancy and should be considered in the differentials in the context of an immunosuppressed patient with radiological findings of a colonic mass.

PMID:38262716 | PMC:PMC10826489 | DOI:10.1136/bcr-2023-257130

Int J Mol Sci. 2024 Jan 13;25(2):1014. doi: 10.3390/ijms25021014.

ABSTRACT

Organoids are self-organized, three-dimensional structures derived from stem cells that can mimic the structure and physiology of human organs. Patient-specific induced pluripotent stem cells (iPSCs) and 3D organoid model systems allow cells to be analyzed in a controlled environment to simulate the characteristics of a given disease by modeling the underlying pathophysiology. The recent development of 3D cell models has offered the scientific community an exceptionally valuable tool in the study of rare diseases, overcoming the limited availability of biological samples and the limitations of animal models. This review provides an overview of iPSC models and genetic engineering techniques used to develop organoids. In particular, some of the models applied to the study of rare neuronal, muscular and skeletal diseases are described. Furthermore, the limitations and potential of developing new therapeutic approaches are discussed.

PMID:38256087 | PMC:PMC10815694 | DOI:10.3390/ijms25021014

BMC Med Genomics. 2024 Jan 22;17(1):29. doi: 10.1186/s12920-024-01801-1.

ABSTRACT

BACKGROUND: X-linked nephrogenic diabetes insipidus (NDI) is a rare genetic renal disease caused by pathogenic variants in the AVPR2 gene. Single nucleotide variants and small insertions/deletions in AVPR2 are reliably detected by routine clinical sequencing. Nevertheless, structural variants involving AVPR2 are challenging to identify accurately by conventional genetic testing. Here, we report a novel deletion of AVPR2 in a Czech family identified for the first time by targeted long-read sequencing (T-LRS).

METHODS: A male proband with X-linked NDI underwent clinical sequencing of the AVPR2 gene that failed and thus indicated possible whole-gene deletion. Therefore, PCR mapping and subsequent targeted long-read sequencing (T-LRS) using a Pacific Biosciences sequencer were applied to search for the suspected deletion. To validate the deletion breakpoints and prove variant segregation in the family with X-linked NDI, Sanger sequencing of the deletion junction was performed. Quantitative real-time PCR was further carried out to confirm the carrier status of heterozygous females.

RESULTS: By T-LRS, a novel 7.5 kb deletion of AVPR2 causing X-linked NDI in the proband was precisely identified. Sanger sequencing of the deletion junction confirmed the variant breakpoints and detected the deletion in the probands´ mother, maternal aunt, and maternal cousin with X-linked NDI. The carrier status in heterozygous females was further validated by quantitative real-time PCR.

CONCLUSIONS: Identifying the 7.5 kb deletion gave a precise molecular diagnosis for the proband, enabled genetic counselling and genetic testing for the family, and further expanded the spectrum of structural variants causing X-linked NDI. Our results also show that T-LRS has significant potential for accurately identifying putative structural variants.

PMID:38254165 | PMC:PMC10804598 | DOI:10.1186/s12920-024-01801-1

Orphanet J Rare Dis. 2024 Jan 22;19(1):23. doi: 10.1186/s13023-023-02986-x.

ABSTRACT

BACKGROUND: Research priorities are best defined through engagement with communities who will be impacted by the research and have lived experience of the topics to be studied. We aimed to establish a pediatric rare disease community stakeholder group and empower them in (1) eliciting perspectives from affected families in the wider region and (2) synthesizing collective ideas into a research agenda focused on shared ethical, legal, and social implications (ELSI) across rare disease.

METHODS: This two-year project utilized a community-centered approach to engage rare disease community members as equal partners in developing a research agenda for ELSI in rare disease. We established "Rare Voices" (RV), a 22-member stakeholder group of patients, parents, clinicians and researchers. Following capacity-building trainings, RV designed and conducted listening sessions with teen patients and parents of children with rare diseases to explore challenges, positive experiences, and ethical concerns. Listening session findings were synthesized and contextualized into research topics, which RV members further refined and prioritized. We used established measures to assess RV member engagement and satisfaction.

RESULTS: From 14 listening sessions with parents (n = 52) and teen patients (n = 13), RV identified eight core research topics as most important for future rare disease research: coordinating care, communication, accessing resources and care, impact on family unit, community and support in society, mental health and identity, ethical aspects of care, and uncertainty. RV members were highly engaged throughout the two-year project and reported high levels of satisfaction with the experience and research agenda.

CONCLUSIONS: Through capacity-building and authentic engagement, this project resulted in a community-led rare disease research agenda to guide future rare disease ELSI research that aligns with patients' and families' priorities. An environment of equal partnership and respect created a space for mutual learning where community members were empowered to shape the research agenda based on their collective experiences. The agenda recognizes the shared psychosocial and healthcare experiences of rare disease and offers practical areas of research to address patient and family needs.

PMID:38254122 | PMC:PMC10801933 | DOI:10.1186/s13023-023-02986-x

Nat Commun. 2024 Jan 22;15(1):657. doi: 10.1038/s41467-024-44980-2.

ABSTRACT

Rare DNA alterations that cause heritable diseases are only partially resolvable by clinical next-generation sequencing due to the difficulty of detecting structural variation (SV) in all genomic contexts. Long-read, high fidelity genome sequencing (HiFi-GS) detects SVs with increased sensitivity and enables assembling personal and graph genomes. We leverage standard reference genomes, public assemblies (n = 94) and a large collection of HiFi-GS data from a rare disease program (Genomic Answers for Kids, GA4K, n = 574 assemblies) to build a graph genome representing a unified SV callset in GA4K, identify common variation and prioritize SVs that are more likely to cause genetic disease (MAF < 0.01). Using graphs, we obtain a higher level of reproducibility than the standard reference approach. We observe over 200,000 SV alleles unique to GA4K, including nearly 1000 rare variants that impact coding sequence. With improved specificity for rare SVs, we isolate 30 candidate SVs in phenotypically prioritized genes, including known disease SVs. We isolate a novel diagnostic SV in KMT2E, demonstrating use of personal assemblies coupled with pangenome graphs for rare disease genomics. The community may interrogate our pangenome with additional assemblies to discover new SVs within the allele frequency spectrum relevant to genetic diseases.

PMID:38253606 | PMC:PMC10803329 | DOI:10.1038/s41467-024-44980-2

Rev Esp Patol. 2024 Jan-Mar;57(1):64-66. doi: 10.1016/j.patol.2023.07.002. Epub 2023 Oct 14.

ABSTRACT

Fraser syndrome or cryptophthalmos-syndactyly syndrome is a rare genetic disease, the diagnosis of which is based on a series of major and minor clinical criteria and that can be supported by genetic tests. This article presents the case of a fetal autopsy at 37 weeks of gestation with suspicion of CHAOS syndrome (congenital obstructive syndrome of the upper airways).

PMID:38246713 | DOI:10.1016/j.patol.2023.07.002

Rev Esp Patol. 2024 Jan-Mar;57(1):53-58. doi: 10.1016/j.patol.2023.04.003. Epub 2023 Jul 5.

ABSTRACT

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease with a poor prognosis. It frequently affects the skin; indeed, dermal lesions may be the first clinical manifestation. We report three cases of BPDCN where the patients presented with skin lesions and describe the clinical, histopathological and immunohistochemical findings, its molecular characteristics and metastatic work-up. One of the patients remains in a clinical trial with IMGN632, a molecule directed against CD123, while the other two patients died after different therapeutic regimens. BPDCN is a complex diagnostic challenge which, together with its poor prognosis, requires close clinical-pathological cooperation in order to accelerate its diagnosis and offer early therapeutic alternatives with drugs directed against specific molecular targets.

PMID:38246711 | DOI:10.1016/j.patol.2023.04.003

Medicine (Baltimore). 2024 Jan 19;103(3):e37005. doi: 10.1097/MD.0000000000037005.

ABSTRACT

RATIONALE: A huge hypertrophic scar formation secondary to chronic ingrown toe nail mimicking tumor is a rare disease. It is not only causing concerns cosmetically, but also hindering normal daily activities physically and socially. In this paper, we present an unusual case of bilateral ingrown nails with different phases. One resulted in a large hypertrophic scar caused by stimulation from secondary to chronic ingrown nail.

PATIENT CONCERNS AND DIAGNOSIS: A 44-year-old man with a huge mass (7 × 4 × 8.5 cm) in his right great toe and inflamed ingrown nail in his left great toe visited the clinic. The mass in the right toe showed an irregular and bizarre shape with a stellate ulcer (2 × 2 cm) at the distal end. After removing an ingrown nail 3 years ago with minor repetitive trauma, self-managed wound has grown into a tumor-like mass, resulting in intolerable discomfort. In gross appearance, a stalk appeared to originate from the lateral side of the nail bed with the ingrown nail in the great toe showing inflamed medial and lateral gutter and causing redness and tenderness. Huge hypertrophic scar formation secondary to chronic ingrown toe nail mimicking tumor is a rare disease that is not only causing a cosmetic concern, but also hindering normal daily activities physically and socially.

INTERVENTION AND OUTCOMES: Excisional biopsy was performed for both great toes. Biopsy confirmed chronic ulcerative inflammation with a hypertrophic scar. The resection site healed and persisted well at 12 months after surgery.

CONCLUSION: Our unusual case suggests that the natural course of an untreated ingrown toe nail may result in hypertrophic scar extending far to mimic tumorous conditions.

PMID:38241575 | PMC:PMC10798770 | DOI:10.1097/MD.0000000000037005

Medicine (Baltimore). 2024 Jan 19;103(3):e36920. doi: 10.1097/MD.0000000000036920.

ABSTRACT

RATIONALE: Pure white cell aplasia (PWCA) is a rare paraneoplastic syndrome that occurs in patients with thymomas. Currently, the pathogenesis and treatment of this disease remain in the exploratory stage.

PATIENT CONCERNS: We report a 68-year-old woman with thymoma experienced PWCA involvement as her first presentation. The patient had high fever and agranulocytosis at the onset of the disease. The white blood cell count in the complete blood count was 1.9 × 109/L with a neutrophil of 0.1 × 109/L. The bone marrow aspirates showed decreased granulocyte proliferation. Computed tomography showed a large mass in the anterior mediastinum.

DIAGNOSES: The final diagnosis of our patient was PWCA and thymoma.

INTERVENTIONS: She underwent a thymectomy and cyclosporine A administration during first remission.

OUTCOMES: Long-term remission was achieved following the readministration of cyclosporine A after the disease recurrence.

LESSONS: PWCA or agranulocytosis with thymoma has been confirmed to be an extremely rare disease. Thymomas with PWCA correlate with autoimmunity. From this case study and the literature review, we concluded that the pathogenesis of thymomas in PWCA is mainly related to the activation of autoreactive T cells. Thymectomy and the immunosuppressive drug, cyclosporine A, were chosen for treatment. The patient's granulocyte levels were unable to recover after surgery because of the inability to promptly clear activated T cells. After surgery, cyclosporine A continued to take for a long time. Thymectomy combined with prolonged cyclosporine A administration may be an effective method for treating this rare disease.

PMID:38241556 | PMC:PMC10798751 | DOI:10.1097/MD.0000000000036920

Orphanet J Rare Dis. 2024 Jan 18;19(1):18. doi: 10.1186/s13023-024-03018-y.

ABSTRACT

BACKGROUND: Vascular anomalies (VAs) are rare congenital disorders that can cause pain, disfigurement, coagulopathy, asymmetric growth, and disability. Patients with complex VAs experience multiple barriers to accessing expert care. It is imperative to understand which factors support these patients' ability to navigate the healthcare system.

RESULTS: We surveyed adult patients with VAs using previously validated measures, recruiting participants from five patient advocacy groups and multidisciplinary VA clinics. The primary outcome was self-reported ability to access needed medical care, using the "Navigating the Healthcare System" subscale of the Health Literacy Questionnaire. We evaluated factors associated with the ability to navigate the healthcare system using multivariate linear regression (n = 136). We also performed an exploratory model that included the primary care doctor's knowledge of VAs for the subset of participants with a primary care doctor (n = 114). Participants were predominantly women (n = 90, 66%), White and non-Hispanic (n = 109, 73%), and college-educated (n = 101, 73%). Most participants had PIK3CA-Related Overgrowth Spectrum (n = 107, 78%). Most participants reported that navigating the healthcare system was "sometimes" or "usually difficult" (mean score 16.4/30, standard deviation 5.6). In multivariate linear regression, ability to navigate the healthcare system was associated positively with quality of information exchange (β = 0.38, 95% Confidence Interval (CI) 0.22 to 0.55, p <.001) and whether patients had VA specialists (β = 2.31, 95% CI 0.35 to 4.28, p =.021), but not associated with patient self-advocacy, anxiety, education, age, race and ethnicity, gender, or having a primary care doctor. In exploratory analysis of participants with primary care doctors, ability to navigate the healthcare system was positively associated with quality of information exchange (β = 0.27, 95% CI 0.09 to 0.45, p =.004), having a VA specialist (β = 2.31, 95% CI 0.22 to 4.39, p =.031), and primary care doctors' VA knowledge (β = 0.27, 95% CI 0.04 to 0.50, p =.023).

CONCLUSION: Patients with VAs struggle to navigate the healthcare system. High-quality information from clinicians and more knowledgeable primary care doctors might help patients to access needed care. Relying on patient self-advocacy is insufficient. Future efforts should focus on patient-directed and clinician-directed educational interventions. Additionally, future work should assess the structural barriers that impede healthcare access for these patients.

PMID:38238812 | PMC:PMC10797881 | DOI:10.1186/s13023-024-03018-y

medRxiv. 2023 Dec 27:2023.12.22.23300468. doi: 10.1101/2023.12.22.23300468. Preprint.

ABSTRACT

Unsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN) cis-regulatory elements and subsequently nominate candidate non-coding variants in the congenital cranial dysinnervation disorders (CCDDs), a set of Mendelian disorders altering cMN development. We generated single cell epigenomic profiles for ~86,000 cMNs and related cell types, identifying ~250,000 accessible regulatory elements with cognate gene predictions for ~145,000 putative enhancers. Seventy-five percent of elements (44 of 59) validated in an in vivo transgenic reporter assay, demonstrating that single cell accessibility is a strong predictor of enhancer activity. Applying our cMN atlas to 899 whole genome sequences from 270 genetically unsolved CCDD pedigrees, we achieved significant reduction in our variant search space and nominated candidate variants predicted to regulate known CCDD disease genes MAFB, PHOX2A, CHN1, and EBF3 - as well as new candidates in recurrently mutated enhancers through peak- and gene-centric allelic aggregation. This work provides novel non-coding variant discoveries of relevance to CCDDs and a generalizable framework for nominating non-coding variants of potentially high functional impact in other Mendelian disorders.

PMID:38234731 | PMC:PMC10793524 | DOI:10.1101/2023.12.22.23300468

J Med Chem. 2024 Feb 8;67(3):1690-1700. doi: 10.1021/acs.jmedchem.3c02165. Epub 2024 Jan 17.

ABSTRACT

Expedited development and approval pathways at the Food and Drug Administration (FDA) such as Priority review, Fast Track Designation, Breakthrough Designation, and Accelerated Approval are programs available to drug sponsors that aim to incentivize and expedite the delivery of drugs to patients in need. In addition, other incentive programs such as Orphan Drug Designation (ODD), Qualified Infectious Disease Product Designation (QIDP), and Rare Pediatric Disease Designation (RPDD) are available to drug sponsors to help motivate development of drugs that may have lower economic incentive for commercialization. These programs have been largely effective, and many new innovative drugs since 2010 have accessed these programs. This Perspective highlights how these programs have been used in recent FDA drug approvals and discusses future ways sponsors and regulatory agencies may further enable development of these innovative drugs in the most expeditious fashion.

PMID:38233132 | DOI:10.1021/acs.jmedchem.3c02165

Pediatr Neurol. 2023 Nov 23;152:63-72. doi: 10.1016/j.pediatrneurol.2023.11.005. Online ahead of print.

ABSTRACT

BACKGROUND: Trofinetide was approved by the US Food and Drug Administration for the treatment of Rett syndrome (RTT) in March 2023. Benefiting the ability to communicate in RTT is often identified as the most important caregiver goal for new therapies. This analysis reports the communication-related end points from the phase 3 LAVENDER study of trofinetide in RTT.

METHODS: Females with RTT, aged five to 20 years, were randomized 1:1 to trofinetide or placebo for 12 weeks. Secondary efficacy end points related to communication were based on change from baseline to week 12 and included the caregiver-rated Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist (CSBS-DP-IT) Social Composite score (key secondary end point; scores ranged from 0 to 26 [higher scores indicated better communication]) and novel clinician rating scales (0 [normal] to 7 [severe impairment]) measuring the ability to communicate choices nonverbally (RTT-COMC) and verbally (RTT-VCOM).

RESULTS: Trofinetide demonstrated a statistically significant difference versus placebo for the CSBS-DP-IT Social Composite score (least squares mean [LSM] difference = 1.0; 95% confidence interval [CI], 0.3 to 1.7; P = 0.0064; Cohen's d effect size = 0.43) and a nominally significant difference for the RTT-COMC (LSM difference: -0.3; 95% CI, -0.6 to -0.0; P = 0.0257; Cohen's d effect size = 0.36). As expected, there was no difference for the RTT-VCOM.

CONCLUSIONS: Significant treatment benefit for trofinetide versus placebo was observed in scales measuring the ability to communicate. These scales may be appropriate for future clinical studies in RTT and other neurodevelopmental disorders.

PMID:38232652 | DOI:10.1016/j.pediatrneurol.2023.11.005

J Clin Immunol. 2024 Jan 17;44(2):47. doi: 10.1007/s10875-023-01644-y.

ABSTRACT

PURPOSE: Inborn errors of immunity (IEI) represent a heterogeneous group of rare genetically determined diseases. In some cases, patients present with complex or atypical phenotypes, not fulfilling the accepted diagnostic criteria for IEI and, thus, at high risk of misdiagnosis or diagnostic delay. This study aimed to validate a platform that, through the opinion of immunologist experts, improves the diagnostic process and the level of care of patients with atypical/complex IEI.

METHODS: Here, we describe the functioning of the IEI-Virtual Consultation System (VCS), an innovative platform created by the Italian Immunodeficiency Network (IPINet).

RESULTS: In the validation phase, from January 2020 to June 2021, 68 cases were entered on the IEI-VCS platform. A final diagnosis was achieved in 35/68 cases (51%, 95% CI 38.7 to 64.2). In 22 out of 35 solved cases, the diagnosis was confirmed by genetic analysis. In 3/35 cases, a diagnosis of secondary immunodeficiency was made. In the remaining 10 cases, an unequivocal clinical and immunological diagnosis was obtained, even though not substantiated by genetic analysis.

CONCLUSION: From our preliminary study, the VCS represents an innovative and useful system to improve the diagnostic process of patients with complex unsolved IEI disorders, with benefits both in terms of reduction of time of diagnosis and access to the required therapies. These results may help the functioning of other international platforms for the management of complex cases.

PMID:38231401 | PMC:PMC10794402 | DOI:10.1007/s10875-023-01644-y

BMC Pediatr. 2024 Jan 8;24(1):28. doi: 10.1186/s12887-023-04492-2.

ABSTRACT

BACKGROUND: Pediatric myelodysplastic syndromes (MDS) are rare disorders with an unrevealed pathogenesis. Our aim is to explore the role of genetic factors in the pathogenesis of MDS in children with different outcomes and to discover the correlation between genetic features and clinical outcomes as well as disease characteristics.

METHODS: We conducted an analysis of archived genetic data from 26 patients diagnosed with pediatric MDS at our institution between 2015 and 2021, examining the association between different genetic characteristics and clinical manifestations as well as prognosis. Additionally, We presented three cases with distinct genetic background and outcomes as examples to elaborate the role of genetic factors in pediatric MDS with different prognoses.

RESULTS: Genetic variations were detected in 13 out of the 26 patients, including 8 patients with co-occurrence of somatic and germline mutations (CSGMs) and 5 patients with somatic mutations alone. Our analysis revealed that advanced MDS (4/8, 50% vs. 1/5, 20% and 4/11, 36.4%), PD (3/8, 37.5% vs. 1/5, 20% and 1/11 9.1%), and TD (6/8, 75% vs. 2/5, 40% and 2/11, 18.2%) were more common in patients with CSGMs than those with somatic mutations alone or without any mutations. We also found out in our study that 8 patients with CSGMs had evidently different clinical outcomes, and we presented 3 of them as examples for elaboration. Case 1 with germline and somatic mutations of unknown significance had a relatively slow disease course and a good prognosis. Case 2 with compound heterozygous germline SBDS variants and somatic mutations like del20q had a stable disease course and a reversed outcome. Case 3 with a germline GATA2 variant and somatic mutations including - 7 had a rapidly progressive disease course and a worst prognosis.

CONCLUSION: Our findings indicate that genetic background of pediatric MDS is closely linked with disease characteristics as well as outcomes and that CSGMs may lead to disease progression. It should be emphasized that the interaction between certain germline variants and somatic mutations, such as SBDS and del20q, may result in hematopoietic stem cell adaptation (improved hematopoiesis) and reversed clinical outcomes, which can facilitate the development of targeted therapy.

PMID:38191334 | DOI:10.1186/s12887-023-04492-2

BMJ Case Rep. 2024 Jan 8;17(1):e258045. doi: 10.1136/bcr-2023-258045.

ABSTRACT

Extramammary Paget disease is a rare dermatological condition resembling Paget disease that occurs most commonly in the anogenital area and axilla. We present the case of an elderly male who had come with complaints of an itchy, erythematous and raised lesion in the perianal region for 3 months that did not respond to antifungals. A biopsy was taken from the lesion site and the diagnosis was confirmed by histopathological examination. It is important to be aware of conditions like extramammary Paget disease when an elderly individual presents with a non-specific pruritic lesion in the perianal area that is non-responsive to treatment; the diagnosis of which can be made only by doing a biopsy from the concerned site. This highlights the importance of histopathological examination in such ambiguous cases.

PMID:38191219 | DOI:10.1136/bcr-2023-258045