Table 2.

Disorders to Consider in the Differential Diagnosis of vEDS

DiffDx DisorderGene(s)MOIClinical Features of DiffDx Disorder
Overlapping w/vEDSDistinguishing from vEDS
Classic EDS COL5A1
COL5A2 1		ADTypically not assoc w/blood vessel, bowel, or organ rupture
  • Soft, doughy, stretchy skin
  • Abnormal scars
  • Significant large-joint hypermobility
Ehlers-Danlos classic/vascular type COL1A1 ADPathogenic variants in COL1A1 (all result in substitutions of arginine by cysteine in the triple helical domain) have been reported in persons w/classic EDS & aneurysm & dissection of large vessels 1Similar to classic EDS
Kyphoscoliotic EDS
(See FKBP14-kEDS & PLOD1-kEDS.)		 PLOD1
FKBP14 		ARVascular rupture may be a feature
  • Progressive scoliosis
  • Hypotonia
  • Fragility of the globe
Periodontal Ehlers-Danlos syndrome C1R
C1S 		ADBruising & skin staining, particularly shins
  • Rare
  • Features of classic EDS + early periodontal friability, recession, & tooth loss
Isolated arterial aneurysmSee footnote 2.Single arterial aneurysm or dissectionUsually NOT the result of a type III collagen defect
Loeys-Dietz syndrome SMAD2
SMAD3
TGFB2
TGFB3
TGFBR1
TGFBR2 		AD
  • Vascular findings (cerebral, thoracic, & abdominal arterial aneurysms &/or dissections)
  • Aggressive arterial aneurysms & high incidence of pregnancy-related complications
  • Thin translucent skin & easy bruising
  • Skeletal manifestations
  • Craniofacial anomalies
  • Predisposition to allergic disease
Polycystic kidney disease, autosomal dominant (ADPKD) PKD1
PKD2 3 		ADVascular abnormalities: intracranial aneurysms, aortic root dilatation, & thoracic aorta dissection; mitral valve prolapse
  • Generally late onset
  • Bilateral renal cysts & cysts in other organs
  • Abdominal wall hernias
  • Renal manifestations: hypertension, renal pain, & renal insufficiency
Marfan syndrome FBN1 ADConsider Marfan syndrome if presenting vascular complication is an aortic aneurysm or dissection.
  • vEDS & Marfan syndrome usually can be distinguished relatively easily on physical exam.
  • Persons w/Marfan syndrome typically have dolichostenomelia & arachnodactyly, lens dislocation, & dilatation or aneurysm of only the aorta.

AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; EDS = Ehlers-Danlos syndrome; MOI = mode of inheritance

1.

A COL1A1 pathogenic variant p.Arg134Cys was identified in two unrelated children with classic EDS [Nuytinck et al 2000]. The same substitution was subsequently identified in three unrelated persons with aneurysms and rupture of medium-sized arteries in young adulthood. These individuals also had thin and hyperextensible skin, easy bruising, and abnormal wound healing [Malfait et al 2007; Malfait & De Paepe, personal observation]. Pathogenic variants in COL1A1, however, are not a major cause of classic EDS [Malfait et al 2005]. See EDS, Classic Type.

2.

Familial forms of arterial aneurysm have been linked to at least 16 identified genes (see Heritable Thoracic Aortic Disease Overview).

3.

Pathogenic variants GANAB and DNAJB11 may also be associated with ADPKD in rare cases (see ADPKD).

From: Vascular Ehlers-Danlos Syndrome

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