Types of Ehlers-Danlos Syndrome

An introduction to the rare and ultra-rare forms of EDS. Each subtype is caused by specific genetic mutations that affect collagen and related proteins.

aEDS BCS cvEDS cEDS clEDS dEDS kEDS mcEDS mEDS pEDS spEDS vEDS

The 12 genetically defined subtypes of Ehlers-Danlos Syndrome

Arthrochalasia EDS

aEDS

COL1A1 or COL1A2

Caused by mutations at specific locations in ONE copy of COL1A1 or COL1A2

Defining Features

  • Congenital bilateral hip dislocation
  • Severe generalized joint hypermobility
  • Subluxations and dislocations
  • Loose, stretchy, thin feeling skin
  • Skin fragility
  • Curvatures of the spine
  • Bone fragility
  • Hypotonia
  • Craniofacial features
  • Motor delay
  • Foot deformities

Brittle Cornea Syndrome

BCS

ZNF469 or PRDM5

Caused by mutations at specific locations in BOTH copies of ZNF469 or PRDM5

Defining Features

  • Thin, fragile cornea
  • Ocular rupture
  • Keratoconus/keratoglobus
  • Blue sclera
  • High myopia
  • Hearing loss
  • Craniofacial features
  • Small joint hypermobility
  • Hip dysplasia
  • Marfanoid habitus
  • Foot deformities
  • Scoliosis, kyphosis, and/or lordosis

Cardiac-Valvular EDS

cvEDS

COL1A2

Caused by mutations at specific locations in BOTH copies of COL1A2

Defining Features

  • Severe cardiac valve abnormalities
  • Severe generalized joint hypermobility
  • Loose, stretchy, thin feeling skin
  • Skin fragility
  • Joint contractures
  • Atrophic scarring
  • Easy bruising

Classical EDS

cEDS

COL5A1, COL5A2, or COL1A1

Caused by mutations at specific locations in ONE copy of COL5A1, COL5A2, or COL1A1

Defining Features

  • Significant wound healing complications like dehiscence, severe atrophic scarring, and failure to progress through stages of wound healing
  • Severe generalized joint hypermobility
  • Subluxations/dislocations
  • Easy bruising with hemosiderin staining
  • Bilateral piezogenic papules
  • Skin fragility
  • Hernia(s)
  • Subcutaneous spheroids
  • Acrogeria
  • Redundant skin on the joints
  • Hallux Valgus
  • Scoliosis
  • Organ prolapse
  • Epicanthal folds

Classical-Like EDS

clEDS

TNXB or AEBP1

Caused by mutations at specific locations in BOTH copies of TNXB (Type 1) or AEBP1 (Type 2)

Type 1 (TNXB)

Defining Features
  • Stretchy, velvety skin
  • Absence of atrophic scarring
  • Generalized joint hypermobility
  • Easy bruising
  • Hand and foot deformities
  • Muscle weakness
  • Axonal polyneuropathy
  • Gastrointestinal fragility
  • Vascular fragility
  • Purpura
  • Edema

Type 2 (AEBP1)

Defining Features
  • Stretchy skin
  • Atrophic scarring
  • Generalized joint hypermobility
  • Easy bruising
  • Cardiovascular disease
  • Hair loss
  • Osteopenia
  • Gastrointestinal features

Dermatosparaxis EDS

dEDS

ADAMTS2

Caused by mutations at specific locations in BOTH copies of ADAMTS2

Defining Features

  • Severe redundant, stretchy, loose, or lax skin
  • Severe skin fragility
  • Craniofacial features
  • Increased palmar or plantar wrinkling
  • Umbilical hernia or hernia(s)
  • Joint hypermobility
  • Gross motor delay
  • Ocular fragility
  • Cardiovascular fragility

Kyphoscoliotic EDS

kEDS

PLOD1 or FKBP14

Caused by mutations at specific locations in BOTH copies of PLOD1 or FKBP14

Defining Features

  • Severe kyphoscoliosis
  • Muscle hypotonia
  • Joint hypermobility
  • Eye involvement/scleral and ocular fragility
  • Head and foot deformities
  • Severity, soft, doughy skin with widened scarring
  • Atrophic scarring
  • Arterial aneurysm
  • Craniofacial features
  • Marfanoid habitus
  • Osteopenia/osteoporosis

Musculocontractural EDS

mcEDS

CHST14 or DSE

Caused by mutations at specific locations in BOTH copies of CHST14 or DSE

Defining Features

  • Congenital multiple contractures
  • Palatal erosion
  • Peculiar finger shapes
  • Progressive spinal and foot deformities
  • Craniofacial features
  • Large subcutaneous hematomas
  • Eye involvement

Myopathic EDS

mEDS

COL12A1

Caused by mutations at specific locations in ONE or BOTH copies of COL12A1

Defining Features

  • Muscle weakness and/or atrophy in infancy or childhood
  • Distal joint hypermobility
  • Hyperelasticity and atrophic scarring
  • Soft, doughy skin
  • Myopathy on muscle biopsy

Periodontal EDS

pEDS

C1R or C1S

Caused by mutations at specific locations in ONE copy of C1R or C1S

Defining Features

  • Severe, early-onset periodontitis
  • Pretibial plaques
  • Joint hypermobility
  • Bone marrow abnormalities
  • Stretchy, fragile skin
  • Atrophic scars
  • Recessing gums

Spondylodysplastic EDS

spEDS

B4GALT7, B3GALT6, or SLC39A13

Caused by mutations at specific locations in BOTH copies of B4GALT7, B3GALT6, or SLC39A13

Defining Features

  • Craniofacial features
  • Short stature
  • Mild craniofacial surface abnormalities
  • Joint hypermobility
  • Bowing of limbs
  • Foot deformities
  • Multisystem abnormalities
  • Skin abnormalities
  • Hyperopia
  • Hypotonia
  • Nephro/hydronephrosis
  • Dental abnormalities

Vascular EDS

vEDS

COL3A1 or COL1A1

Caused by mutations at specific locations in ONE copy of COL3A1 or COL1A1

Defining Features

  • Arterial aneurysm or rupture
  • Fragility of hollow organs
  • Gastrointestinal rupture
  • Carotid-cavernous sinus fistula
  • Thin, translucent skin
  • Acrogeria
  • Hypermobility of small joints
  • Organ prolapse

Sources

Brady AF, Demirdas S, Fournel-Gigleux S, Ghali N, Giunta C, Kapferer-Seebacher I, et al. The Ehlers-Danlos syndromes, rare types. Am J Med Genet C Semin Med Genet. 2017;175(1):70-115.

Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8-26.

Angwin C, Ghali N, et al. Ehlers-Danlos syndromes, rare types: Clinical and molecular review. Eur J Hum Genet. 2023;31(2):131-142.

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