06. tbl. 98. árg. 2012

Ehlers-Danlos syndrome type IV. Case study and clinical findings

Ehlers-Danlos heilkenni af gerð IV. Sjúkratilfelli og sjúkdómseinkenni

We describe Ehlers-Danlos syndrome type IV in adult patients with a confirmed diagnosis and a systematic review of expected clinical findings in the disease. Serious complications were found in four individuals, two with gastrointestinal perforation at the age of 32 years, two had died from an aortic rupture (34 and 44 years old) and one has been diagnosed with aortic root dilatation. Most had also less severe clinical features such as varicose veins, easy bruising, thin and translucent skin, chronic joint subluxation or dislocation or pes planus. None of the females had uterine rupture or premature birth. Management and surveillance options were reviewed.

Gudmundsdottir SA1, Möller PH1,2, Arngrimsson R1,3

1Faculty of Medicine, University of Iceland.2Department of Surgery, Landspitali - University Hospital, Reykjavik, Iceland 3Department of Genetics and Molecular Medicine, Landspitali - University Hospital, Reykjavik, Iceland.

Table I: Classification of Ehlers-Danlos syndromes. Adapted from Beigton et al 1and Germain et al 10




Clinical symptoms Inheri-tance Gene
Classic type EDS I

Smooth velvety skin. Easy

bruising. Wide atrophic scars.

Joint hypermobility.Lesser effect on internal organs

Autosomal dominant COL5A1
EDS II Same as EDS I but milder COL5A2




Soft, smooth and velvety skin.

Joint hypermobility.Recurrent joint dislocation.Chronic joint pain.

Autosomal dominant Unknown
Vascular type EDS IV Thin, translucent skin. Easy bruising. Arterial intestinal, uterine rupture.Characteristic facial appearance. Autosomal dominant COL3A1




Severe hypotonia at birth.

Scoliosis.Scleral fragility or

rupture of eye globe.

Autosomal recessive





EDS VIIA EDS VIIB Congenital dislocated hips. Severe joint hypermobility. Recurrent subluxations. Autosomal dominant




paraxia type


Severe skin fragility. Easy

bruising. Hernias.

Autosomal recessive N-protease deficiency


Text Box: Major diagnostic criteria - Arterial rupture - Intestinal rupture - Uterine rupture - Positive family history Minor diagnostic criteria - Thin, translucent skin - Bruising - Characteristic facial apperance - Acrogeria - Hypermobility of small joints - Tendon and muscle rupture - Varicose veins - Arteriovenous, carotid-cavernous sinus fistula - Pneumothorax, pneumohemothorax - Recurrent joint subluxation, dislocation - Congenital hip dislocation - Clubfoot - Gingival recession Table II: Villefranche diagnostic criteria for EDS IV. The presence of any two or more major criteria is highly indicative of clinical diagnosis. Minor diagnostic criteria contribute to the diagnosis of the specific subtype. Adapted from Beigton et al.1



Table III. Clinical symptoms and general health of patients with  EDS-IV in the family.



Face Skin Joints Vessels Other


  Bruising.   Sudden death due to aortic dissection DNA test not performed


Thin, delicate straight nose, thin lips. Thin, translucient and fragile skinBruising.

Pes planus.

Clicking in jaw. Hammer toe.

Severe surgical bleeding.

Varicose veins.

Mesentrial artery occlusion.


Intestinal rupture

2°perineal rupture following vaginal birth.

DNA testing positive



      Dissection and rupture of abdominal aorta. DNA test not performed.


  Prominent veins.  

Cerebrala arterio-venous

malformation. Cerebral hemorrhage.

Negative DNA test.



Thin, delicate straight nose, thin lips.

Blue sclera.

Thin, translucient, fragile skin. Easy bruising.

Pes planus.

Recurrent joint dislocation.Chronic joint pains.

Easy brushing. Varicose veins.


Intestinal rupture. Pelvic adhesions.


Positve DNA test

III-5 Thin, delicate straight nose, thin lips.

Thin, fragile

skinProminent veins on chest.

Instable knee joint.

Varicose veins.


Perineal rupture following vaginal birth.

Heavy menustral periods.

Positve DNA test

III-4 Thin, delicate straight nose, thin lips.

Stretch marks.



Pes planus. Varicose veins.

Aortic root dilation (4,1cm)


Positive DNA test.


Thin, delicate straight nose, thin lips.



Joint hypermobility.

Pes planus.

Jaw locking.

Joint pain.



Painful, heavy menstrual periods.

Perineal rupture following vaginal birth.

Symphysis pubis dysfunction.

Positive DNA test.



Figure 1. All individuals with a confirmed EDS IV diagnosis can from the same familiy.

Figure 2. Photographs of participants with joint hypermobility.

(A) Only one individual had hyperextension in the elbow joints.

(B) Hypermobility in metacarpophalangeal joints (MCP) was identified in two individuals.

(C) Three participants had hypermobile distal interphalangeal joints (DIP).

Figure 3. Photographs of skin and vascular symptoms in parcipicants.

(A) Veins are visible beneath the skin, particularly on the chest and abdomen.

(B) Petechiae on the skin after hair removal treatment.

(C) Closeup of the skin petechiae, pinpoint non blanching spots.


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