Pathogenic mechanisms in genetically defined Ehlers-Danlos syndromes.

Area of Science:

• Genetics
• Molecular Biology
• Cell Biology

Background:

• Ehlers-Danlos syndromes (EDS) are rare genetic disorders characterized by skin hyperextensibility, joint hypermobility, and tissue fragility.
• Thirteen EDS types are recognized, stemming from genetic defects in 20 genes impacting collagen structure and function.
• EDS pathogenesis involves alterations in the extracellular matrix (ECM) and cellular dynamics.

Purpose of the Study:

• To provide a comprehensive overview of current knowledge on EDS pathogenesis.
• To detail extracellular, pericellular, and intracellular alterations in EDS.
• To synthesize findings from molecular analyses and animal models.

Main Methods:

• Narrative review of existing literature.
• Analysis of molecular data from patient samples (dermal fibroblasts).
• Inclusion of studies on relevant animal models.

Main Results:

• Genetic defects in EDS disrupt collagen biosynthesis, organization, and assembly within the ECM.
• Impaired cellular dynamics are implicated in the pathogenesis of EDS.
• Alterations occur at extracellular, pericellular, and intracellular levels.

Conclusions:

• EDS pathogenesis is complex, involving multifaceted disruptions in connective tissue at various cellular and extracellular levels.
• Further research is needed to fully understand the extent of (extra)cellular consequences in EDS.
• This review consolidates current understanding to guide future research and clinical approaches.