EDS Genetics

There is no “collagen type” of EDS. All six distinct subtypes of EDS are caused by different defects in collagen synthesis.

All share joint laxity, soft skin, easy bruising, and some systemic manifestations. Joint laxity results in widespread chronic pain, joint instability and spontaneous subluxations/dislocations. Each type is thought to involve a unique defect in connective tissue, although not all of the genes responsible for causing EDS have been identified.

Mutations for the six main types of EDS:

Hypermobile: although the cause of most HM is still unknown, Haploinsufficiency of TNXB Is Associated with Hypermobility Type of Ehlers-Danlos Syndrome http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1180584/ this is probably a cause of some forms of Hypermobile type – and at least one family with HM had COL3A1 mutation.

Vascular is COL3A1mutation, and a newer form of COL3A1 haploinsufficiency results in a variety of Ehlers-Danlos syndrome type IV with delayed onset of complications and longer life expectancy http://www.ncbi.nlm.nih.gov/pubmed/21637106

Classical is COL5A1, COL5A2

Kyphoscoliosis is PLOD1 (deficiency of an enzyme called lysyl hydroxylase – considered extremely rare – last count was 60 families)

Arthrochalasis COL1A1, COL1A2 (very extremely rare – last count was 30 families)

Dermatosparaxis ADAMTS2 (ten cases)

From NIH http://ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome one can find labs doing which genetic testing (sequencing, deletion/duplication, prenatal, and/or carrier testing):

Gene Tests Arthrochalasia http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/2070

Gene Tests: Ehlers-Danlos Syndrome, Classic Type, COL1A1-Related http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/319558

Gene Tests: Ehlers-Danlos Syndrome, Classic Type, COL5A1-Related http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/319188

Gene Tests: Ehlers-Danlos Syndrome, Classic Type, COL5A2-Related http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/319189

Gene Tests: Ehlers-Danlos Syndrome, Hypermobility Type http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/3263 (don’t know what these are testing, actually — I assume the COL3A1 HM mutation, but I’m not sure)

Gene Tests: Ehlers-Danlos Syndrome, Kyphoscoliotic Form http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/3038

Gene Tests: Ehlers-Danlos Syndrome, Musculocontractural Type http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/319374

Gene Tests: Ehlers-Danlos Syndrome Type IV http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/2067

Gene Tests: Ehlers-Danlos Syndrome Type VIIA http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/319158

Gene Tests: Ehlers-Danlos Syndrome Type VIIB http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/319159

WIKIPEDIA http://en.wikipedia.org/wiki/Ehlers–Danlos_syndrome goes into more detail about obscure mutations:


“The large number of distinct types of the Ehlers–Danlos syndrome that have already been identified indicates great heterogeneity, but clearly that heterogeneity is not exhausted by the present classification.” [James, William D.; Berger, Timothy G.; Elston, Dirk M. (2006). Andrews’ diseases of the skin: clinical dermatology (10th ed.). Philadelphia: Saunders. p. 512. ISBN 978-0-7216-2921-6].

Forms of EDS within this category may present with soft, mildly stretchable skin, shortened bones, chronic diarrhea, joint hypermobility and dislocation, bladder rupture, or poor wound healing. Inheritance patterns within this group include X-linked recessive, autosomal dominant, and autosomal recessive. Examples of types of related syndromes other than those above reported in the medical literature include:

http://omim.org/entry/305200 – Type 5

http://omim.org/entry/130080 – Type 8 – unspecified gene, locus 12p13

http://omim.org/entry/225310 – Type 10 – unspecified gene, locus 2q34

http://omim.org/entry/608763 – Beasley-Cohen type

http://omim.org/entry/130070 – Progeroid form – B4GALT7

http://omim.org/entry/606408 – Due to Tenascin-X deficiency – TNXB

http://omim.org/entry/130090 – Type unspecified

EDS can be either inherited or can be de novo. De novo means the genetic mutation occurred spontaneously in utero.

“EDS, classic type is inherited in an autosomal dominant manner. It is estimated that approximately 50% of affected individuals have inherited the disease-causing mutation from an affected parent, and approximately 50% of affected individuals have a de novo disease-causing mutation.” http://www.ncbi.nlm.nih.gov/books/NBK1244/


“About 50% of [Vascular EDS] affected individuals have inherited the COL3A1 mutation from an affected parent, and about 50% of affected individuals have a de novo disease-causing mutation.” http://www.ncbi.nlm.nih.gov/books/NBK1494/

Because all the genetic mutations for the Hypermobility type of EDS are not yet known, it is not known the percentage of individuals with inherited cases versus those with de novo cases.

Other thoughts?

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.