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.

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

• dorsiflexion of the 5th finger at more than 90°, the forearm being horizontal
• passive opposition  of the thumb on the anterior face of the forearm
• elbow hyperextension at more than 10° 
• hyperextension of the knee to more than 180°
• bending of the trunk with the palms of the hands placed on the ground
• unusual spinal flexibility

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')

Peculiarities:

• classical form: variable joint hyperlaxity, which can decrease with age. Typical appearance of the skin: fluffy appearance, hyperextensible, molluscoid pseudotumors ; hernias; incompetent cervix;  uterine or anal prolapse; vascular complications and mitral prolapse are rare (6 %); risk of spontaneous pneumothorax
• hypermobile form: joint hyperlaxity dominates the clinical picture. Early scoliosis, sometimes early osteoarthritic lesions secondary to repeated dislocations; few cutaneous signs; dilatation of the aortic arch in 10%; frequent autonomic signs: delayed gastric emptying, orthostatic hypotension, irritable bowel (see median arcuate ligament syndrome). The hypermobile form may be associated to congenital adrenal hyperplasia (see this term and the CAH-X syndrome)
• vascular form: the most dangerous form because there is a risk of vascular pseudoaneurysms (carotid arteries, iliac, visceral branches of the aorta) and spontaneous perforation of viscera (especially the sigmoid colon); the skin is very thin and the superficial vessels are visible by transparency; little stretchable skin and the laxity of the joints is often absent; clubfeet in 12 % of cases and congenital dislocation of the hip in 3 % of cases; often short stature
• cyphoscoliotic form (2 %): causes hypotonia and kyphoscoliosis starting from the neonatal period; clubfeet in 30%; hyperextensible skin and joint hyperlaxity with frequent dislocations ; risk of glaucoma, keratoconus, and retinal detachment
• arthrochalasic form (very rare): joint hyperlaxity with frequent dislocations; congenital dislocation of the hip, contractures of extremities, thoracolumbar scoliosis with secondary short stature; frequent fractures; fragile and hyperextensible skin
• dermatosparaxis: see this term
• spondylocheirodysplasia: short stature; blue sclerae; late eruption of teeth and hypodontia. Joint hyperlaxity and bone abnormalities: platyspondyly, short and wide femoral neck, wide femoral metaphyses etc.; hyperextensible skin; slow wound healing
• musculo-contractural form: 1) facial dysmorphism: wide forehead, small mouth and micrognathia in childhood but prognathism in adolescence, blue sclerae,  low implanted ears, long philtrum. (2) severe kyphoscoliosis; (3) feet with some fingers contractures; (4) hypotonia and hyperextensible skin
• the type V, X-linked: causes many orthopedic abnormalities
• type VIII: causes early hypodontia
• the type IX, X-linked: is due to a disorder of cellular metabolism of Cu
• type X: due to plasma fibronectin deficiency, it causes a decrease in platelet aggregability; could be similar, for some authors, to the form XI or to the 'benign hypermobile joint syndrome'
• progeroid form: associates signs of spondyloepimetaphyseal dysplasia (see this term) and hypermobility of joints: facial dysmorphism, micrognathia, kyphoscoliosis, anomaly of the cervical spine, cleft palate, muscular hypotonia with contracture of the hands, platyspondyly, cutis laxa. Several cases of type I have been described in the Reunion Island.

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 (fragile cornea and retina); avoid the use of a tourniquet (risk of hematoma and compartment syndrome when the tourniquet is released). Avoid any friction on the skin: loosely adhesive dressings, blood pressure  cuff. 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:

-        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 prophylactically.
The use of a neuraxial block carries a difficulty to evaluate the risk of bleeding and hematoma (frequent presence of dural ectasias), and an increased risk of dural tap,  due to the presence of Tarlov's cysts (see this term) 

In the hypermobile form: check the mobility of the cervical spine and mouth opening; subluxations and recurrent dislocations of the jaw can lead to temporomandibular joint ankylosis; gentle laryngoscopy to avoid  luxation of the jaw; sometimes: instability of the occipito-atlo-axoidal joint. While it seems that local anesthesia by infiltration is less effective (mutation at the Na channel ?), both successful and failed neuraxial and peripheral blocks have been reported. 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 case of associated congenital adrenal hyperplasia, the perioperative doses of cortisone should be adapted (see congenital adrenal hyperplasia)

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.

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Updated: May 2023