Archives of Dermatological Research

, Volume 311, Issue 4, pp 265–275 | Cite as

Understanding the basis of Ehlers–Danlos syndrome in the era of the next-generation sequencing

  • Francesca CortiniEmail author
  • Chiara Villa
  • Barbara Marinelli
  • Romina Combi
  • Angela Cecilia Pesatori
  • Alessandra Bassotti


Ehlers–Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) defined by joint laxity, skin alterations, and joint hypermobility. The latest EDS classification recognized 13 subtypes in which the clinical and genetic phenotypes are often overlapping, making the diagnosis rather difficult and strengthening the importance of the molecular diagnostic confirmation. New genetic techniques such as next-generation sequencing (NGS) gave the opportunity to identify the genetic bases of unresolved EDS types and support clinical counseling. To date, the molecular defects have been identified in 19 genes, mainly in those encoding collagen, its modifying enzymes or other constituents of the extracellular matrix (ECM). In this review we summarize the contribution of NGS technologies to the current knowledge of the genetic background in different EDS subtypes.


Ehlers–Danlos syndrome Heterogeneity Heritable connective tissue disorders 



Thanks to AISED for support and Dr. Bice Strumbo and Dr. Agostino Seresini for excellent technical assistance.


There is no funding source.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Clinical Sciences and Community HealthUniversity of Milan, IRCCS Ca’ Granda FoundationMilanItaly
  2. 2.Department of Medicine Preventive ServicesUOC Occupational Medicine, IRCCS Ca’ Granda FoundationMilanItaly
  3. 3.School of Medicine and SurgeryUniversity of Milano-BicoccaMonzaItaly
  4. 4.Regional Center of Ehlers-Danlos SyndromeIRCCS Ca’ Granda FoundationMilanItaly

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