Ehlers Danlos Syndrome
From Iusmgenetics
Contents |
[edit] Ehlers Danlos Syndrome
[edit] General background information
- Like Achondroplasia and Osteogenesis imperfecta, a disorder of collagen / connective tissue.
- Like OI, there are a number of different types.
- Types 1, 4, 6, and 9 are the ones on which we will focus.
[edit] Mode of inheritance
- Type 1: AD (abnormal type 5 collagen)
- Type 4: AD (abnormal type 3 collagen)
- Type 6: AR (decreased crosslinking)
- Type 9: XR (decreased crosslinking)
- As is often the case, recessive conditions reflect a deficiency of some sort.
- Here there is a deficiency in lysyl hydroxylase (type 6) or copper binding / lysyl oxidase (type 9).
[edit] Single important gene
- Type 1: col5a; abnormal type 5 collagen (abnormal type 5 collagen)
- Type 4: col3a1; abnormal type 3 collagen (homotrimer, mutations in glycines, dominant negative effect)
- Type 6: plod; lysyl hydroxylase deficiency (decreased crosslinking)
- Type 9: mnk; copper binding / lysyl oxidase (decreased crosslinking)
[edit] Etiology
- Type 1: abnormal type 5 collagen
- Type 4: abnormal type 3 collagen
- homotrimer
- mutations in glycines
- dominant negative effect
- Type 6: decreased crosslinking
- Type 9: decreased crosslinking
[edit] Pathogenesis
[edit] Phenotypic information
- Increased elasticity of skin (hyperextensibility).
- Increased fragility.
- Thin skin.
- Abnormal scarring ("cigarette paper" scars).
- Joint laxity (hypermobility).
- Fragility of major arteries
- May predispose pts to increased surgical risk and / or sudden death.
- Type 4: arteries and colon especially affected
