{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:55:42Z","timestamp":1761746142363,"version":"build-2065373602"},"reference-count":63,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T00:00:00Z","timestamp":1755302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health to IRCCS Policlinico San Donato"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Fatigue is a highly prevalent and burdensome symptom among individuals with Marfan syndrome (MFS), yet its heterogeneity and underlying psychosocial and clinical correlates remain underexplored. This study aimed to identify and characterize distinct fatigue-related profiles in MFS patients using a data-driven cluster analysis approach. Methods: A cross-sectional study was conducted involving 127 patients with MFS from a specialized connective tissue disorder center in Italy. Participants completed self-reported measures of fatigue severity (Fatigue Severity Scale, FSS), depressive symptoms (Patient Health Questionnaire-9, PHQ-9), and insomnia (Insomnia Severity Index, ISI). The body mass index (BMI) and clinical data were also collected. A t-distributed stochastic neighbor embedding (t-SNE) analysis was performed to reduce dimensionality, followed by hierarchical clustering (Ward\u2019s method), exploring solutions from k = 2 to k = 10. The optimal cluster solution was identified based on silhouette scores and clinical interpretability. Results: Three distinct clusters emerged: (1) a cluster characterized by low fatigue with minimal psychological and sleep-related symptoms (younger patients, lower PHQ-9 and ISI scores), (2) a cluster characterized by moderate fatigue with moderate psychological and sleep-related symptoms (intermediate age, moderate PHQ-9 and ISI scores), and (3) a cluster characterized by high fatigue with elevated psychological and sleep-related symptoms (older patients, higher PHQ-9, ISI, and FSS scores). Significant differences were observed across clusters in age, BMI, depressive symptoms, insomnia severity, and fatigue levels (all p &lt; 0.05). Conclusions: Our findings highlight the heterogeneity of fatigue experiences in MFS and suggest the importance of profiling patients to guide personalized interventions. This approach may inform precision medicine strategies and enhance the quality of life for individuals with this rare disease.<\/jats:p>","DOI":"10.3390\/jcm14165802","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T15:34:53Z","timestamp":1755531293000},"page":"5802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phenotyping Fatigue Profiles in Marfan Syndrome Through Cluster Analysis: A Cross-Sectional Study of Psychosocial and Clinical Correlates"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9013-9326","authenticated-orcid":false,"given":"Nathasha Samali","family":"Udugampolage","sequence":"first","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"},{"name":"Cardiovascular Genetic Centre, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacopo","family":"Taurino","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetic Centre, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8325-6057","authenticated-orcid":false,"given":"Alessandro","family":"Pini","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetic Centre, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9286-1825","authenticated-orcid":false,"given":"Edward","family":"Callus","sequence":"additional","affiliation":[{"name":"Clinical Psychology Service, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy"},{"name":"Department of Biomedical Sciences for Health, University of Milan, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0440-6940","authenticated-orcid":false,"given":"Arianna","family":"Magon","sequence":"additional","affiliation":[{"name":"Health Professions Research and Development Unit, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8171-8203","authenticated-orcid":false,"given":"Gianluca","family":"Conte","sequence":"additional","affiliation":[{"name":"Health Professions Research and Development Unit, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giada","family":"De Angeli","sequence":"additional","affiliation":[{"name":"Clinical Research Service, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Angolani","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetic Centre, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Paglione","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"},{"name":"Clinical Research Service, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1326-8642","authenticated-orcid":false,"given":"Irene","family":"Baroni","sequence":"additional","affiliation":[{"name":"Clinical Research Service, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Iozzo","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7736-6209","authenticated-orcid":false,"given":"Rosario","family":"Caruso","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Warnink-Kavelaars, J., De Koning, L., Rombaut, L., Alsem, M., Menke, L., Oosterlaan, J., Buizer, A., Engelbert, R., and on behalf of the Pediatric Heritable Connective Tissue Disorders Study Group (2021). 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