Different types of Ehlers-Danlos syndrome [14].
| Types (n = 13) | Genes | Protein | Inheritance | Onset | Criteria |
|---|---|---|---|---|---|
| Classic | COL5A1, COL5A2, COL1A1 | Procollagen | AD | Childhood | Hyperextensibility with atrophic scarring, GHM |
| Classic-like (Type 1 ?) | TNXB | Tenascin-X | AR | Childhood and young adulthood | Skin hyperextensibility (velvet) without atrophic scarring, GHM, with/without recurrent dislocations, occurrence of haematomas |
| Cardiac and valvular involvement | COL1A2α2(I) | Procollagen | AR | Childhood, sometimes as early as the neonatal period | Severe progressive heart valve problems, skin hyperextensibility with atrophic scarring, thin skin, bruising, GHM |
| Vascular involvement | COL3A1, COL1A1α1(III) | Procollagen, α1(I) procollagen | AD | Childhood, sometimes as early as the neonatal period | - |
| Hypermobility | Not known | Not known | AD (?) | Any age | - |
| Arthrochalasia | COL1A1, COL1A2 | α1(I) procollagen, α2(I) procollagen | AR | Childhood, sometimes as early as the neonatal period | - |
| Dermatosparaxis | ADAMTS2 | Complement subcomponents 1r and 1s | AD | Childhood, sometimes as early as the neonatal period | Extreme, congenital skin fragility, characteristic craniofacial features, postnatal growth retardation, short limbs, redundant lax skin with excessive folds (especially palmar), severe bruising, with increased risk of subcutaneous haematomas and haemorrhages, umbilical hernias, perinatal complications due to tissue fragility |
| Kyphoscoliotic | PLOD1, FKBP14 | Lysyl hydroxylase 1, FKBP22 | AR | Childhood | Congenital muscular hypotonia, Early kypho-scoliosis, GHM with dislocations/subluxations |
| Corneal thinning | PRDM5, ZNF469 | PR-domain containing protein 5, zinc finger protein 469 | AR | Young children, some as early as the neonatal period | Thin cornea with or without rupture, early, progressive keratoconus, early progressive keratoglobus, blue sclera |
| Spondylodysplasia | B3GALT6, B4GALT7, SLC39A13 | Galactosyltransferase I and II, ZIP13 | AR | Neonatal period | Short stature, muscle hypotonia, GHM, curvature of the extremities |
| Muscle contractures | CHST14, DSE | Dermatan-4-sulfotransferase 1, dermatan sulfate epimerase 1 | AR | Childhood, sometimes as early as the neonatal period | Congenital contractures (particularly adducted thumbs, talipes equino-varus); characteristic facial features; hyperextensibility of the wrinkled skin (palmar) with atrophic scarring, haemorrhages |
| Myopathy | COL12A1α1(XII) | Procollagen | AD | Childhood, sometimes as early as the neonatal and prenatal periods | Congenital muscle hypotonia and/or atrophy, which improves with age, joint contractures (proximal), joint hypermobility (distal) |
| Periodontal involvement | C1R, C1S | Complement subcomponents 1r and 1s | - | Childhood | Early-onset, severe, untreatable periodontitis. Absence of gingival attachment, pretibial plaques, positive first-degree family history |
| Candidates for new clinical subtypes | |||||
| Classic-like (Type 2 ?) | AEBP1 | AE-binding protein 1 | AD | Childhood and early adulthood | Bilateral ptosis, webbed skin at the nape of the neck, low receding hairline, sagging cheeks, large ears, narrow high palate |
| Overlap associated with COL1 | COL1A1, COL1A2 | α1(I) procollagen, α2(II) procollagen | AD, AR | Childhood and early adulthood | Blue sclerae, flat feet with rearfoot valgus deformity, GHM, soft, doughy and/or hyperextensible skin |
n = 13 refers to the main clinical subtypes; two additional candidate subtypes are listed separately. AD: autosomal dominant; AE: adipocyte enhancer; AR: autosomal recessive; GHM: generalized hypermobility. ? It was left as is, following the reference.