Orphanet Journal of Rare Diseases最新文献

Background: Hypohidrotic ectodermal dysplasia (HED) includes some rare congenital disorders affecting the skin, its appendages, and the teeth. Although hypohidrosis can be life-threatening, research on the impact of HED on the patient's quality of life has been very limited so far. Aiming at the development of a condition-specific patient-reported outcome measure (PROM) assessing health-related quality of life (HRQoL), we studied the HRQoL of children and adolescents with HED.

Methods: Focus (group) interviews were conducted with patients at the age of 8 to 17 years and parents of patients aged 2-17 years, all recruited from the HED patient registry of the University Hospital Erlangen, Germany. A qualitative interview analysis was performed, identifying key themes and generating a category system based on relevant interview excerpts. Using the Card-sorting method, an item list for the pilot version of the questionnaire was made.

Results: Eleven focus (group) interviews with 9 children/adolescents and 22 parents provided information on 24 patients. The analysis identified 562 statements about HRQoL, which were categorized into six main domains: physical well-being, emotional well-being, social well-being, autonomy, childcare/school/education, and parental well-being. On the basis of these statements, age-adjusted pilot versions of a questionnaire were developed, consisting of 83 items each: (1) an observer report for parents of children aged 2-7 years, (2) a self-report combined with an observer report for children and adolescents aged 8-17 years.

Conclusions: This study is the first to explore HRQoL of children and adolescents with HED through qualitative interviews. Our findings highlight the impact of heat intolerance on daily life, the emotional burden of physical limitations, and the crucial role of coping strategies, social inclusion, and supportive relationships. The final validation of the new PROM, which shall enable the systematic integration of patient perspectives into clinical practice and research, is underway.

Osteosarcoma is a highly malignant bone tumor, and a subset of cases is closely associated with hereditary syndromes. These syndrome-related osteosarcomas exhibit unique clinical features, molecular mechanisms, and therapeutic challenges. This review summarizes the current understanding of specific types of syndrome-related osteosarcomas, including those associated with Rothmund-Thomson syndrome, Li-Fraumeni syndrome, secondary osteosarcoma in retinoblastoma survivors, Werner syndrome, and Bloom syndrome. These syndromes are typically characterized by specific gene mutations or chromosomal instability, significantly increasing the risk of osteosarcoma development. However, the rarity and heterogeneity of syndrome-related osteosarcomas pose significant challenges for diagnosis and treatment, including difficulties in early detection, incomplete elucidation of molecular mechanisms, and limitations of conventional therapeutic approaches. This article aims to systematically review the clinical characteristics, molecular mechanisms, and therapeutic challenges of these syndromes, providing a comprehensive reference for clinicians and directions for future research.

Objective: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive stenosis or occlusion of the internal carotid artery, with an abnormal vascular network forming as compensation. The etiology of MMD remains largely unknown, though genetic and immune factors have been implicated. This study aimed to investigate the landscape of peripheral immune cells in MMD patients using single-cell RNA sequencing (scRNA-seq) to identify potential biomarkers and mechanisms involved in the disease.

Methods: Peripheral blood mononuclear cells (PBMCs) were collected from six MMD patients and three controls. scRNA-seq was performed to analyze the transcriptomic profiles of various immune cell populations. Differential gene expression, functional enrichment, and cell interaction analyses were conducted to identify significant alterations in immune cell subpopulations. Additionally, trajectory analysis was used to explore the differentiation pathways of monocytes in MMD.

Results: The study identified significant transcriptional alterations in peripheral immune cells, particularly in monocytes and natural killer (NK) cells. Notably, intermediate monocytes (Mono_CD14_CD16) were increased in MMD patients compared to controls. Functional enrichment analysis revealed upregulation of genes related to immune cell activation and signal transduction in MMD. Two previously uncharacterized genes, RETN and TGFBR2, were identified as potential biomarkers. Trajectory analysis suggested that classical monocytes may differentiate into intermediate monocytes in MMD. Cell interaction analysis highlighted the role of Mono_CD14_CD16 cells in mediating immune responses through interactions involving RETN and TGF-β signaling pathways.

Conclusions: This study provides a comprehensive analysis of peripheral immune cell alterations in MMD, highlighting the involvement of monocyte subpopulations and specific signaling pathways in disease pathogenesis. The findings offer new insights into the immune dysregulation in MMD and suggest potential targets for diagnosis and treatment.