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. 2024 Dec 3;36(4):235-245.
doi: 10.1515/medgen-2024-2061. eCollection 2024 Dec.

Genetic diagnosis of the Ehlers-Danlos syndromes

Johannes Zschocke  1 , Serwet Demirdas  2 , Fleur S van Dijk  3
Affiliations

Genetic diagnosis of the Ehlers-Danlos syndromes

Johannes Zschocke et al. Med Genet. .

Abstract

The Ehlers-Danlos syndromes (EDS) represent a group of genetically diverse disorders characterized by the variable combination of joint hypermobility, hyperextensibility of the skin, and connective tissue fragility affecting the skin and other organs. Based on clinical features, 13 different types of EDS have been delineated, 12 of which represent monogenic conditions caused by pathogenic variants in 21 confirmed genes. Pathogenesis is related to disturbances of collagen formation and/or stability. No monogenic cause has been identified for hypermobile EDS (hEDS), a more common EDS type, which is unlikely to represent a single gene disorder in the majority of affected individuals and at present cannot be diagnosed by genetic investigations. Here we summarize the clinical features and the molecular bases of the monogenic EDS types, highlight diagnostic challenges, and provide guidance for the molecular work-up of affected individuals. In general, genetic tests are indicated if clinical features suggest a monogenic EDS type but are usually unrewarding for other cases of hypermobility.

Keywords: EDS; Ehlers-Danlos syndrome; gene panel; genetic testing; hypermobility; organ rupture; skin fragility; skin hyperextensibility.

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Conflict of interest statement

Competing interests: Authors state no conflict of interest.

Figures

Figure 1:
Figure 1:
Genomic structure of the RCCX locus 1a: normal genomic structure; genes depicted in grey are pseudogenes. 1b: typical 32–33 kb deletion found in CAH-X syndrome
Figure 2:
Figure 2:
Genetic differential diagnosis of generalized joint hypermobility and suspected Ehlers-Danlos-Syndrome
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