Ehlers Danlos Syndrome (EDS)
The Collagen Diagnostic Laboratory offers diagnostic testing for EDS types IV and VII only. The table below and references outlines the clinical features and present knowledge of the molecular basis of all forms of EDS.| Type | Revised Classification | Clinical Features | Inheritance | Molecular Defect | Testing |
| I:Gravis | Classical type | Soft, velvety, hyperextensible skin;easy bruising; "cigarette paper" scarsprematurity | AD | COL5A1, COL5A2 mutations | COL5A1 and COL5A2 sequencing studies (not available in CDL) |
| II: Mitis | Classical type | Similar to EDS type I but less severeSoft, hyperextensible skin, joint hypermobility, bruising, normal scar formation | AD(AR, rare)AR | COL5A1, COL5A2 mutations | COL5A1 and COL5A2 sequencing studies (not available in CDL) |
| III: Familial hypermobility | Hypermobility type | Soft skin, no scarring, marked large and small joint hypermobility | AD | Not known(Rare: COL3A1 G637S) | None |
| IV: Arterial | Vascular type | Thin, translucent skin with visible veins; marked bruising; skin and jointshave normal extensibility; arterial, bowel and uterine rupture. | AD | COL3A1 mutations | 1. Collagen screening of cultured fibroblasts; mutation identification for patients with positive protein studies** |
| V: X-linked | Removed to "Other" category | Similar to EDS type II | XLR | Not known | None |
| VI: Ocular | Ocular-scoliotic type | Soft, velvety, hyperextensible skin;hypermobile joints, scoliosis; ocular fragility and keratoconus | AR | PLOD1 gene mutations | Urinary pyridinoline cross-links screening. (not avail in CDL) |
| VII: A and B Arthrochalasis multiplex congenita | Arthrochalasia type | Congenital hip dislocation, joint hypermobility; soft skin with normalscarringVery soft, fragile, bruisable skin, marked joint hypermobility, blue sclerae, small jaw, hypertrichosis | AD | A: COL1A1 exon 6 splice site mutations; | Collagen screening of cultured fibroblasts identifies EDS VIIA, EDS VIIB and EDS VIIC. Targeted molecular testing of COL1A1/2 exon 6. |
| VIII: Periodontal | Removed to "other category" | Generalized periodontitis; skin similar to EDS type II | AD | Not known | None |
| IX: X-linked cutis laxa; occipital horn syndrome | Removed from EDS phenotypes | Soft, extensible, lax skin; bladder diverticulae and rupture; short arms, limited pronation and supination, broad clavicles, occipital horns | XLR | ATP7A gene mutations, allelic to Menkes syndrome | Serum copper and ceruloplasm studies. (not available in CDL) |
| X: Fibronectin defect | Removed to "other" category | Similar to EDS type II | AR | Defect in fibronectin | None |
Modified from Byers 2000 in The Metabolic & Molecular Bases of Inherited Disease
**If collagen screening studies are requested and the biochemical results are consistent with vascular EDS, cDNA sequencing will be initiated automatically to confirm the diagnosis. In these instances cDNA sequencing is completed on the segments of the COL3A1 cDNA suspected to house the mutation based on collagen testing.
References:
Ehlers-Danlos Syndrome (EDS) - General
Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (
Byers PH The Metabolic & Molecular Basis of Inherited Disease 8th Edition Volume IV 2000 Disorders of Collagen Biosynthesis and Structure p 5241-85.
Byers PH and Schwarze U. Principles and Practices of Medical Genetics 4th Edition Ehlers-Danlos syndrome. P. 4021-68.
EDS type I/II - Classical type
De Paepe A et al. Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I and II. Am J Hum Genet. 1997 Mar;60(3):547-54.
Schwarze U et al. Null alleles of the COL5A1 gene of type V collagen are a cause of the classical forms of Ehlers-Danlos syndrome (types I and II). Am J Hum Genet. 2000 Jun;66(6):1757-65.
Wenstrup RJ et al. COL5A1 haploinsufficiency is a common molecular mechanism underlying the classical form of EDS. Am J Hum Genet 2000 Jun;66(6):1766-76.
EDS type I/II - Classical Form - Tenascin X deficiency
Schalkwijk J et al. A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency. N Engl J Med. 2001 Oct 18;345(16):1167-75.
EDS type IV- Vascular type
Pepin MG and Byers PH Genetests LINK
Pepin M et al.Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med. 2000 Mar 9;342(10):673-80.
EDS type VI - Lysyl Hydroxylase Deficiency
Wenstrup RJ et al. Ehlers-Danlos syndrome type VI: clinical manifestations of collagen lysyl hydroxylase deficiency. J Pediatr. 1989 Sep;115(3):405-9.
Yeowell HN et al. Mutational analysis of the lysyl hydroxylase 1 gene (PLOD) in six unrelated patients with Ehlers-Danlos syndrome type VI: prenatal exclusion of this disorder in one family. Hum Mutat. 2000 Jul;16(1):90.
Pasquali M et al. Abnormal formation of collagen cross-links in skin fibroblasts cultured from patients with Ehlers-Danlos syndrome type VI. Proc Assoc Am Physicians. 1997 Jan;109(1):33-41.
EDS type VIIA and B Arthrochalasia
Giunta C et al. Ehlers-Danlos syndrome type VII: clinical features and molecular defects. J Bone Joint Surg Am. 1999 Feb;81(2):225-38. Review.
Byers PH et al. Ehlers-Danlos syndrome type VIIA and VIIB result from splice-junction mutations or genomic deletions that involve exon 6 in the COL1A1 and COL1A2 genes of type I collagen. Am J Med Genet. 1997 Oct 3;72(1):94-105.
EDS type VIIC - Dermatospraxis
Smith LT et al. Human dermatosparaxis: a form of Ehlers-Danlos syndrome that results from failure to remove the amino-terminal propeptide of type I procollagen. Am J Hum Genet. 1992 Aug;51(2):235-44.
Colige A et al. Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene. Am J Hum Genet 1999 Aug;65(2):308-17.