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Herein, we present a cross-sectional study on a cohort of 75 cEDS patients from 44 families with a confirmed molecular diagnosis focusing on the diagnostic criteria recognized in the current EDS nosology and on additional mucocutaneous, osteoarticular, musculoskeletal, cardiovascular, gastrointestinal, uro-gynecological, neuropsychiatric, atopic, and facial/ocular features, in order to investigate the multisystemic involvement and natural history of the disorder