Ehlers-Danlos Syndromes (EDS)

 

Epidemiology and Etiology:

·         Clinically and genetically heterogenous group of disorders

·         Defect in the synthesis or structure of fibrillar collagen

·         All 3 Mendelian patterns of inheritance

·         6 clinical variants:

·         Classical (I/II) (AD)

·         Hypermobility (III) (AD)

·         Vascular (IV) (AD)

·         Kyphoscoliosis (VI) (AR)

·         Arthrochalasia (VIIa,b) (AD)

·         Dermatosparaxsis (VIIc) (AR)

 

Common sites:

·          

 

Gross features:

·         Skin

·         Hyperextensible

·         Fragile, vulnerable to trauma

·         Ligaments

·         Joints

·         Hypermobile

·         Thumb hyperextends to forearm

·         Knee bends forwards to almost a right angle

·         dislocations

·         colon

·         rupture (vascular variant)

·         large arteries (vascular variant)

·         rupture

·         eye (kyphoscoliosis variant)

·         corneal rupture

·         retinal detachment

·         diaphragmatic hernia (classical)

 

Histologic features:

·          

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

 

 

 

 

Molecular features:

·         Gene defects:

·         Classical (I/II) (AD)

·         Collagen type V mutations (30-50%):

·         COL5A1

·         COL5A2

·         Unknown mutations

·         Hypermobility (III) (AD)

·         unknown

·         Vascular (IV) (AD)

·         COL3A1

·         At least 3 different mutations

·         Kyphoscoliosis (VI) (AR)

·         Lysyl-hydroxylase

·         Enzyme necessary for hydroxylation of lysine residues during collagen synthesis

·         Essential for the cross-linking of collagen fibres

·         Arthrochalasia (VIIa,b) (AD)

·         Defect in the conversion of type 1 procollagen to collagen

·         COL1A1

·         COL1A2

·         Dermatosparaxsis (VIIc) (AR)

·         Defect in the conversion of type 1 procollagen to collagen

·         Procollagen

·         N-peptidase

·          

 

Other features:

·         Clinical findings:

·         Classical (I/II)

·         Skin and joint hypermobility

·         Atrophic scars

·         Easy bruising

·         Hypermobility (III)

·         Joint hypermobility

·         Joint pain

·         dislocations

·         Vascular (IV)

·         Thin skin

·         Arterial or uterine rupture

·         Bruising

·         Small joint hyperextensibility

·         Kyphoscoliosis (VI)

·         Hypotonia

·         Joint laxity

·         Congenital scoliosis

·         Ocular fragility

·         Arthrochalasia (VIIa,b)

·         Severe joint hypermobility

·         Skin changes mild

·         Scoliosis

·         Bruising

·         Dermatosparaxsis (VIIc)

·         Severe skin fragility

·         Cutis laxa

·         bruising

·          

 

References:

·         Kumar V, Fausto N, Abbas A. Robbins & Cotran Pathologic Basis of Disease, Seventh Edition. 7th ed. Saunders; 2004.