Type (Historic Category) |
Genetic Mutations |
Major Features |
Inheritance Pattern |
Salient Histologic/Ultrastructural Features |
Classic (I, II) |
COL5A1, COL5A2.
COL1A1 |
Skin hyperextensibility with atrophic scarring, GJH |
AD |
Flower-like collagen fibrils |
Classic-like |
TNXB |
Skin hyperextensibility without atrophic scarring, easy bruising, GJH |
AR |
|
Cardiac valvular |
COL1A2 |
Cardiac valvular disease, classic skin involvement, joint hypermobility |
AR |
|
Hypermobile (III) |
Mostly unknown, partially due to TNXB
heterozygous |
Joint hypermobility, less skin involvement, abdominal hernia, pelvic organ prolapse, aortic root dilatation |
AD |
Calcified deposits within an amorphous matrix of elastic fibers and clusters of hyaluronic acid |
Vascular (IV) |
COL3A1 |
Early arterial rupture, sigmoid colon perforation, gestational uterine rupture, peripartum perineum laceration, carotidcavernous sinus fistula, family history of vascular Ehlers-Danlos syndrome (vEDS) |
AD |
Thin dermis, irregular thickness of dermal-epidermal junction, fibroblasts with lysosome |
Kyphoscoliotic (VIA) |
PLOD1. FKBP14 |
Congenital hypotonia, congenital or earlyonset kyphoscoliosis, GJH |
AR |
Subtle irregularities in collagen fibril contour and spacing |
Musculocontractural (VIB) |
CHST14. DSE |
Characteristic congenital contractures, characteristic facies, classic skin involvement with palmar wrinkling |
AR |
Dispersal of collagen fibrils |
Arthrochalasia (VIIA, VIIB) |
COL1A1, COL1A2 |
Congenital bilateral hip dislocation, severe
GJH, skin hyperextensibility |
AD |
Collagen fibrils with variable diameter and highly irregular contour |
Dermatosparaxis (VIIC) |
ADAMTS2 |
Extreme congenital skin fragility, characteristic facies, lax skin with palmar wrinkling, severe bruisability, umbilical hernia, growth retardation, short appendages, perinatal complications |
AR |
Hieroglyphic collagen fibrils |
Periodontal (VIII) |
C1R, C1S |
Severe periodontitis, detached gingiva, pretibial plaques, family history of periodontal Ehlers-Danlos syndrome (pEDS) |
AD |
|
Spondylodysplastic |
B4GALT7.
B3GALT6.
SLC39A13 |
Short stature, congenital hypotonia, limb bowing |
AR |
|
Brittle cornea syndrome |
ZNF469. PRDM5 |
Thin cornea, keratoconus, keratoglobus, blue sclera |
AR |
|
Myopathic |
COL12A1 |
Congenital hypotonia with/without atrophy, joint contractures, hypermobility of distal joints |
AD or AR |
|
Abbreviations: AD, autosomal dominant; AR, autosomal recessive; GJH, generalized joint hypermobility. Roman numerals in parentheses represent former numerical designations. Adapted 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; Byers PH, Murray ML. Ehlers-Danlos syndrome: a showcase of conditions that lead to understanding matrix biology. Matrix Biol. 2014;33:10-15; Ong K-T, Plauchu H, Peyrol S, et al. Ultrastructural scoring of skin biopsies for diagnosis of vascular Ehlers-Danlos syndrome. Virchows Arch. 2012;460(6): 637-649; Rohrbach M, Vandersteen A, Yiş U, et al. Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation. Orphanet J Rare Dis. 2011;6:46; Janecke AR, Li B, Boehm M, et al. The phenotype of the musculocontractural type of Ehlers-Danlos syndrome due to CHST14 mutations. Am J Med Genet A. 2016;170A(1):103-115. | |