Ehlers-Danlos, syndromes

Group of hereditary diseases of the connective tissue caused by structural abnormalities of collagen. Prevalence:1/5,000 to 1/10,000. Formerly, the classification distinguished more than 10 subtypes. 

The disease variably affects the skin, the joints and the vessels: the diagnosis is therefore sometimes made when a complication occurs.


digestive tract

hernias, diverticula, rupture (colonic)

vessels

aneurysms, arterial rupture

heart

prolapsus of the mitral valve

uterus

premature delivery,  premature rupture of the amniotic membranes, uterine rupture 

eyes

microcornea, retinal detachment

muscles and bones

osseous and articular pain, luxation


The most common symptoms are: 

-         the joint hyperlaxity: (jaw, knee, shoulder) dislocations are frequent but easy to reduce;

-         fragility and hyper-elasticity of the skin (= can be stretched at least 4 cm without resistance at the level of the neck or the anterior face of the forearm) which is thin and has a fluffy appearance,. 

-         easy bruising,

-         molluscoid pseudotumors at the level of scars and pressure points

-        a fragile dentition,

-         an increased incidence of mitral valve prolapse.


Beighton's hypermobility score is often used to assess the modification of the connective tissue: joint laxity is present if the score is at least 5/9



A  more clinical classification, so-called "Villefranche" is used nowadays (see table where this classification has been expanded with recent discoveries). It happens that certain clinical forms combine the signs of two different types. The main differential diagnosis is with the benign familial hyperlaxity ('benign hypermobile joint syndrome')


New terminology

Old terminology

Autosomal
transmission

Mutated
genes

Affected 
protein

OMIM

Formes classiques

Classical
(1 on 20 to 40.000)

type I (severe: 43%) 

ou II  (minor: 35%)

dominant, but 2/3 of the cases are de novo mutations

COL5A1, 

COL5A2

collagen V and I

130 000

130 010

Hypermobile
(1 on 10 to 15.000)

type III (10%)

dominante

recessive

?

TNX-B

?

tenascine-X-5

130 020

225 320

606 408


Vascular

(1 on 100 to 200.000)

type IV (< 5%)
 Sack-Barabas Syndrome

dominant, but 50% of the cases are de novo mutations

COL3A1

   procollagen III

130 050

Formes moins fréquentes

Cyphoscoliotic

(< 60 reported cases)

type VIa

recessive

PLOD-1

deficiency in lysil-hydroxylase1
+ scoliosis

225 400

Arthrochalasic
(< 30 reported cases)

types VIIa 

and VIIb

dominant

COL1A1, 

COL1A2

collagen I


130 060

Dermatosparaxis

(< 10 reported cases)

type VIIc (rare)

recessive

ADAMTS2

deficiency in procollagen I N -terminal peptidase

225 410

Autres formes

non classified

type V (5 %)

X-linked


similar to EDS II

305 200

periodontosis

type VIII

dominant



130 080

occipital horn
syndrome

type IX

X-linked

 


309 400

non classified

 avec deficiency in
fibronectine (type X)

?


deficiency in fibronectin

225 310

non classified

familial hypermobile
syndrome type XI

dominant

XGPT1


147 900

non classified

 progéroid form

recessive 

  5q35.3


  1p36

type 1

B4GALT7


type 2
B3GALT6

deficiency in galactosyltransferase1


deficiency in β-1,3

galactosyltransferase6

130 070

fragile cornea


recessive

ZNF469


229 200

spondylocheirodysplasia

EDS linked
to gene FKBP14

recessive 

FKBP14


612 350

musculocontractural
type I


recessive 

CHST14

dermatan - 4

 - sulfotransférase

601 776

musculocontractural
type II


recessive

DSE


615 539


Peculiarities:


Anesthetic implications: 

In all forms: contact the team who made the diagnosis. There is sometimes a discrepancy between the phenotype and molecular biology.

Ensure correct positioning: eye protection; avoid the use of a tourniquet. The use of a neuraxial block involves a difficult to evaluate  risk of bleeding and hematoma (to be clearly discussed with the patient). Tissue healing is delayed.

Take a detailled a history in relation to hemostasis (easily bleeding, epistaxis, menorrhagia etc) and skin fragility. 

In case of hemostasis disorders:

-  take the advice from a specialist

-         prophylactic administration of desmopressin (Minirin) [0.3 µg/kg IV or 150 µg nasal if < 50 kg] can be effective. Some authors associate tranexamic acid.

In the hypermobile form: check the mobility of the cervical spine and the opening of mouth; subluxations and recurrent dislocations of the jaw can lead to ankylosis of the temporomandibular joint; gentle laryngoscopy to avoid  luxation of the jaw; while it seems that local anesthesia by infiltration is less effective (mutation at the channel Na ?), neuraxial and peripheral blocks have been successfully completed. For peripheral blocks, it is prudent to use ultrasound and to use a path that avoids crossing large muscle masses (risk of hematoma). 

Echocardiography: mitral valve prolapse ?. Risk of pneumothorax. 

In the vascular form: vascular punctures entail a risk of hematoma and aneurysms and should, if possible, be avoided, as well as surgical interventions and  digestive or uterine endoscopies. Echoguided vascular puncture without dilatation of the vessel wall is to be preferred.

In the dermatologic form (dermatosparaxis : see this term), the fragility of the skin is extreme: take precautions similar to those taken in Epidermolysis Bullosa (see this term).

In the progeroid forms: difficult intubation and venous access; fragile bones (risk of fracture). A case of functional abnormalities of the platelets has been reported.


References : 

-         Dubois PE, Veyckemans F, Ledent MM, Michel M, Clément de Cléty S. 
Anaesthetic management of a child with type VIIc Ehlers-Danlos syndrome. 
Acta Anaesthesiol Belg 2001; 52:21-4.

-         Henry C, Geiss S, Wodey E, Pennerath A et al. 
Perforations coliques spontanées révélatrices d’un syndrome d’Ehlers –Danlos de type IV. 
Arch Pediatr 1995 ; 2 : 1067-72.


Updated: July 2018