Clinical Types of Ehlers-Danlos Syndromes
Type | Common Clinical Features | Gene Variants | Molecular Pathophysiology |
|---|---|---|---|
Classical | Fragile skin (velvety or doughy texture) Atrophic scarring Generalized hypermobility | COL5A1 COL5A2 COL1A1 | Collagen structure and processing |
Vascular | Arterial fragility, aneurysm, dissection, rupture Bruising Colonic and uterine, muscular, or tendon rupture Spontaneous pneumothorax | COL3A1 COL1A1 | Collagen structure and processing |
Arthrochalasia | Severe hypermobility with dislocations Congenital hip dislocation (bilateral) Tissue fragility and atrophic scarring | COL1A1 COL1A2 | Collagen structure and processing |
Dermatosparaxis | Extreme skin fragility with loose, excessive skin and severe bruising Characteristic craniofacial features* Short limbs | ADAMTS2 | Collagen structure and processing |
Cardiac valvular | Cardiac valvular insufficiency Hypermobility | COL1A2 | Collagen structure and processing |
Kyphoscoliotic | Hypotonia Congenital/early-onset kyphoscoliosis Hypermobility | PLOD1 FKBP14 | Collagen folding and crosslinking |
Classical-like Classical-like type 2 (provisional) | Classical-like: Hyperextensible skin (velvety texture); no atrophic scarring Leg edema Classical-like type 2: Hyperextensible skin with atrophic scarring Generalized hypermobility Osteopenia Both: Foot deformities† | Classical-like: TNXB Classical-like type 2: AEBP1 | Classical-like: Myomatrix structure and function Classical-like type 2: Collagen and extracellular matrix formation |
Myopathic | Hypotonia Contractures Hypermobility | COL12A1 | Myomatrix structure and function |
Musculocontractural | Multiple contractures Characteristic craniofacial features* Fragile, hyperextensible skin with easy bruising | CHST14 DSE | Glycosaminoglycan biosynthesis |
Spondylodysplastic | Progressive short stature Hypotonia Limb bowing Some craniofacial features specific to the affected gene | B4GALT7 B3GALT6 SLC39A13 | Glycosaminoglycan biosynthesis (B4GALT7 and B3GALT6) Intracellular processes (SLC39A13) |
Brittle cornea syndrome | Thin cornea, corneal rupture, retinal detachment Hearing loss | ZNF469 PRDM5 | Extracellular matrix homeostasis |
Periodontal | Severe, early-onset periodontal disease with tooth loss Pretibial plaques Hyperextensible skin with easy bruising | C1R C1S | Complement pathway |
Hypermobile | Generalized joint hypermobility Joint instability Chronic pain | Unknown | Unknown |
* Craniofacial features include large fontanelle, downslanting palpebral fissures, and blue sclerae; others vary by Ehlers-Danlos syndrome type. | |||
† Foot deformities include broad forefoot, brachydactyly, pes planus, bunions, and heel papules. | |||
Data from The Ehlers-Danlos Society. 2017 EDS International Classification; Malfait F, Castori M, Francomano CA, Giunta C, Kosho T, Byers PH. The Ehlers-Danlos syndromes. Nat Rev Dis Primers. 2020;6(1):64. Published 2020 Jul 30. doi:10.1038/s41572-020-0194-9; and from Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8-26. doi:10.1002/ajmg.c.31552. | |||