Ehlers-Danlos Syndromes, Joint Hypermobility and Hypermobility Spectrum Disorders

Abstract

Ehlers-Danlos syndrome is an umbrella term for a clinically and genetically heterogeneous group of hereditary soft connective tissue disorders mainly featuring abnormal cutaneous texture (doughy/velvety, soft, thin, and/or variably hyperextensible skin), easy bruising, and joint hypermobility. Currently, musculoskeletal manifestations related to joint hypermobility are perceived as the most prevalent determinants of the quality of life of affected individuals. The 2017 International Classification of Ehlers-Danlos syndromes and related disorders identifies 13 clinical types due to deleterious variants in 19 different genes. Recent publications point out the possibility of a wider spectrum of conditions that may be considered members of the Ehlers-Danlos syndrome community. Most Ehlers-Danlos syndromes are due to inherited abnormalities affecting the biogenesis of fibrillar collagens and other components of the extracellular matrix. The introduction of next-generation sequencing technologies in the diagnostic setting fastened patients' classification and improved our knowledge on the phenotypic variability of many Ehlers-Danlos syndromes. This is impacting significantly patients' management and family counseling. At the same time, most individuals presenting with joint hypermobility and associated musculoskeletal manifestations still remain without a firm diagnosis, due to a too vague clinical presentation and/or the lack of an identifiable molecular biomarker. These individuals are currently defined with the term "hypermobility spectrum disorders". Hence, in parallel with a continuous update of the International Classification of Ehlers-Danlos syndromes, the scientific community is investing efforts in offering a more efficient framework for classifying and, hopefully, managing individuals with joint hypermobility.

Keywords: 2017 International Classification; Collagen; Diagnosis; Ehlers-Danlos Syndrome; Extracellular Matrix; Hypermobility Spectrum Disorders; Joint Hypermobility; Management..