Table 4.

Selected Ehlers-Danlos Syndrome (EDS) Subtypes

Disease NameGene(s)MOIClinical Features/Comments
Classic EDS (cEDS)COL5A1
COL1A1 1
  • Some individuals have aortic root enlargement, but progression of the dilatation & predisposition for aortic dissection have not been established. 2
  • No history of sudden death also argues against progressive aortic root dilatation.
Hypermobile EDS (hEDS) Unknown/
Vascular EDS (vEDS)COL3A1
COL1A1 4
AD 5If vEDS is clinically suspected, collagen biochemistry normal, & no COL3A1 or COL1A1 pathogenic variant, consider LDS/molecular analysis of SMAD2, SMAD3, TGFB2, TGFB3, TGFBR1, & TGFBR24
Cardiac-valvular EDS (cvEDS) (OMIM 225320) COL1A2 ARFeatures of cvEDS 6:
  • Joint hypermobility
  • Skin hyperextensibility
  • Severe cardiac valvular defects
Kyphoscoliotic EDS (kEDS) PLOD1 ARIn kEDS:
  • Risk for rupture of medium-sized arteries & respiratory compromise if kyphoscoliosis is severe
  • Aortic dilatation & rupture variably seen

Mutation of COL1A1 is not a major cause of cEDS [Malfait et al 2005]. See EDS, Classic Type.


In most individuals with hEDS, the gene in which mutation is causative is unknown and unmapped. Haploinsufficiency of tenascin-X (encoded by TNXB) has been associated with hEDS in a small subset of affected individuals.


Arginine-to-cysteine pathogenic variants in COL1A1 have been identified in a subset of affected individuals who typically present with aneurysms of the abdominal aorta and iliac arteries reminiscent of vEDS. Distinct abnormalities on collagen electrophoresis are observed [Malfait et al 2007].


vEDS is almost always inherited in an autosomal dominant manner, but rare examples of biallelic inheritance have been reported.


From: Loeys-Dietz Syndrome

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