Multisystemic manifestations in a cohort of 75 classical Ehlers-Danlos syndrome patients: natural history and nosological perspectives

Abstract

Background: The Ehlers-Danlos syndromes (EDS) are rare connective tissue disorders consisting of 13 subtypes with overlapping features including joint hypermobility, skin and generalized connective tissue fragility. Classical EDS (cEDS) is principally caused by heterozygous COL5A1 or COL5A2 variants and rarely by the COL1A1 p.(Arg312Cys) substitution. Current major criteria are (1) skin hyperextensibility plus atrophic scars and (2) generalized joint hypermobility (gJHM). Minor criteria include additional mucocutaneous signs, epicanthal folds, gJHM complications, and an affected firstdegree relative. Minimal criteria prompting molecular testing are major criterion 1 plus either major criterion 2 or 3 minor criteria. In addition to these features, the clinical picture also involves multiple organ systems, but large-scale cohort studies are still missing. This study aimed to investigate the multisystemic involvement and natural history of cEDS through a cross-sectional study on a cohort of 75 molecularly confirmed patients evaluated from 2010 to 2019 in a tertiary referral center. The diagnostic criteria, additional mucocutaneous, osteoarticular, musculoskeletal, cardiovascular, gastrointestinal, uro-gynecological, neuropsychiatric, and atopic issues, and facial/ocular features were ascertained, and feature rates compared by sex and age. Results: Our study confirms that cEDS is mainly characterized by cutaneous and articular involvement, though none of their hallmarks was represented in all cases and suggests a milder multisystemic involvement and a more favorable natural history compared to other EDS subtypes. Abnormal scarring was the most frequent and characteristic sign, skin hyperextensibility and gJHM were less common, all without any sex and age bias; joint instability complications were more recurrent in adults. Some orthopedic features showed a high prevalence, whereas the other issues related to the investigated organ systems were less recurrent with few exceptions and age-related differences.

Ehlers–Danlos syndromes, hypermobility spectrum disorders, and associated co‐morbidities: Reports from EDS ECHO

“…These and more areas of health concern continue to be explored. Recent large population and registry data affirm their high prevalence in EDS and HSD (Boris & Bernadzikowski, 2021;Cederlöf et al, 2016;Demmler et al, 2019;Hakim et al, 2020;Ritelli, Venturini, Cinquina, Chiarelli, & Colombi, 2020;Schubart et al, 2019), and reports also describe similar severity of co-morbidities in hEDS and HSD (Aubry-Rozier et al, 2021;Copetti et al, 2019;Hakim, 2019).…”

Clinical and molecular characteristics of 168 probands and 65 relatives with a clinical presentation of classical Ehlers–Danlos syndrome

“…With regard to the clinical presentation and genotype–phenotype correlations, 86.8% of individuals with causal involvement of type V collagen fulfilled the two major clinical criteria and only 2.4% did not fulfill the minimal set of clinical criteria. Ritelli et al (2020) recently reported a cohort of 75 molecularly confirmed cEDS patients where only 78.7% satisfied the minimal set of clinical criteria. This is considerably lower than in our cohort, suggesting a more heterogenous clinical presentation in their cohort.…”

Сердечно-Сосудистые Проявления Иосложнения При Синдромах Марфана, Лойеса - Дитца, Элерса - Данло

“…Гипоплазию артериальных сосудов, ломкость капилляров, кровоточивость десен, носовые кровотечения, варикозную болезнь вен нижних конечностей, феномен Рейно и ретикулярное ливедо обнаруживают редко у взрослых людей с синдромом Элерса -Данло [48].…”