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 PH^1,2, Arngrimsson R^1,3

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

Type	Former nosology	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
Hypermobility type	EDS III	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
Kyphoscoliosis type	EDS VI	Severe hypotonia at birth. Scoliosis.Scleral fragility or rupture of eye globe.	Autosomal recessive	Lysyl hydroxylase
Arthrochalasia type	EDS VIIA EDS VIIB	Congenital dislocated hips. Severe joint hypermobility. Recurrent subluxations.	Autosomal dominant	COL1A1       COL1A2
Dermatos- paraxia type	EDS VIIC	Severe skin fragility. Easy bruising. Hernias.	Autosomal recessive	N-protease deficiency

 

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.

Case	Face	Skin	Joints	Vessels	Other
I-1 †		Bruising.		Sudden death due to aortic dissection	DNA test not performed
II-1 †	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
II-3 †				Dissection and rupture of abdominal aorta.	DNA test not performed.
II-4 †		Prominent veins.		Cerebrala arterio-venous malformation. Cerebral hemorrhage.	Negative DNA test.
III-2	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.   Bruising.	Pes planus.	Varicose veins.	Aortic root dilation (4,1cm)   Positive DNA test.
III-3	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.