Hypermobile Ehlers-Danlos syndromes: Complex phenotypes, challenging diagnoses, and poorly understood causes

Dev Dyn. 2021 Mar;250(3):318-344. doi: 10.1002/dvdy.220. Epub 2020 Aug 17.

Abstract

The Ehlers-Danlos syndromes (EDS) are a group of heritable, connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. There is phenotypic and genetic variation among the 13 subtypes. The initial genetic findings on EDS were related to alterations in fibrillar collagen, but the elucidation of the molecular basis of many of the subtypes revealed several genes not involved in collagen biosynthesis or structure. However, the genetic basis of the hypermobile type of EDS (hEDS) is still unknown. hEDS is the most common type of EDS and involves generalized joint hypermobility, musculoskeletal manifestations, and mild skin involvement along with the presence of several comorbid conditions. Variability in the spectrum and severity of symptoms and progression of patient phenotype likely depend on age, gender, lifestyle, and expression domains of the EDS genes during development and postnatal life. In this review, we summarize the current molecular, genetic, epidemiologic, and pathogenetic findings related to EDS with a focus on the hypermobile type.

Keywords: Ehlers-Danlos syndrome; hypermobility; musculoskeletal.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age Factors
  • Ehlers-Danlos Syndrome* / diagnosis
  • Ehlers-Danlos Syndrome* / genetics
  • Ehlers-Danlos Syndrome* / metabolism
  • Ehlers-Danlos Syndrome* / pathology
  • Humans
  • Joint Instability* / diagnosis
  • Joint Instability* / genetics
  • Joint Instability* / metabolism
  • Joint Instability* / pathology
  • Sex Factors

Supplementary concepts

  • Ehlers-Danlos syndrome type 3