Síndrome de Ehlers-Danlos Tipo VI Pseudoaneurysm of the popliteal artery in a patient with Type VI Ehlers-Danlos Syndrome

Ehlers-Danlos Syndrome (EDS) is a rare inherited connective tissue disease arising from an abnormality of collagen synthesis. The main feature of EDS is the extreme fragility of connective tissues, which can result in uterine rupture, spontaneous intestinal drilling and vascular diseases such as aneurysms, pseudoaneurysms, arterial dissections and spontaneous ruptures. This paper describes the case of an 11-year-old patient who presented a pulsatile mass in the left popliteal fossa after a minor trauma caused by a soccer ball. A pseudoaneurysm of the popliteal artery was diagnosed with arterial Doppler ultrasound and confirmed using angiography. An exploratory investigation revealed that the artery wall was too weak to allow reconstruction and the proximal artery was ligated. The patient developed severe limb ischemia and after authorization by the family the limb was amputated. Two days after surgery, the patient died as a result of acute thoracic aortic dissection.


INTRODUCTION
Ehlers-Danlos Syndrome is a hereditary disease of the connective tissues characterized by joint hypermobility, fragile skin and hyperextensibility.Type VI is an autosomal recessive variant of the syndrome that is characterized by neonatal kyphoscoliosis, generalized loose joints, fragile skin and severe muscle hypotonia at birth.Biochemically, there is an abnormality of collagen biosynthesis caused by a deficiency of the lysyl hydroxylase enzyme, resulting in a hydroxylation deficiency of lysine and proline residues in the procollagen chains.These residues provide bonding locations for galactose and glucosyl-galactose and also play a role in the reticulation process that gives collagen resistance and traction.[3][4]

CASE DESCRIPTION
An 11-year-old, white, male patient presented with pain and edema in the left lower limb and difficulty walking with onset 5 days previously, after suffering a trauma from a soccer ball.
The patient's parents were consanguineous (first-degree cousins) and had a family history of Type VI Ehlers-Danlos Syndrome.The patient had one brother and one sister with the same condition who were receiving outpatients care from the genetics clinic at the PUC-SP Faculdade de Ciências Médicas e da Saúde (Sorocaba campus).
On physical examination, the patient exhibited difficulties with walking, edema of the left lower limb and a pulsating mass in the popliteal fossa, with distal pulses present.
Doppler ultrasonography showed that the popliteal artery was patent, with triphasic flow, and revealed a large hematoma in the popliteal fossa, with turbulent flow inside.The hematoma was 9 cm in length, extending from a point 3 cm above the knee joint line to a point 6 cm below the line (Figure 1).
Arteriography showed fusiform dilation compatible with a pseudoaneurysm of the popliteal artery (Figure 2).
The decision was taken to treat the patient surgically.A Z-shaped incision was made to provide posterior access to the popliteal vessels and allow direct dissection of the pseudoaneurysm.The extreme fragility of these tissues was notable (Figures 3, 4 and 5).
An attempt at distal anastomosis of the posterior tibial artery was made using the reversed ipsilateral great saphenous vein, but the attempt was unsuccessful because of the fragility of the artery wall.
Proximal anastomosis of the distal superficial femoral artery was attempted, but could not be accomplished because there was no structure that was firm enough to anchor the sutures.
The decision was then taken to ligate the femoral artery, using 2-0 cotton thread, which was extremely difficult because of the fragility of the artery.
The patient was transferred to the ICU where a transfemoral amputation was performed because of ischemia.
The patient died two days after the operation and was sent to the department responsible for assessment of in-hospital deaths, where the cause of death was identified as thoracic hemorrhage caused by dissection of the thoracic aorta.

DISCUSSION
In Ehlers-Danlos Syndrome, the disease is present from birth, but the symptoms, when detected, are identified later in life.To date, 11 variants of the syndrome have been identified and all of these forms exhibit typical clinical characteristics, of varying intensity. 1ype VI, autosomal recessive, Ehlers-Danlos Syndrome is extremely rare.][3][4] Management of these patients includes an annual physical examination, echocardiogram and ultrasound of the carotids and the abdomen.Arteriography is only indicated if embolization is suspected.Vascular complications include spontaneous rupture, dissection and dissecting aneurysms. 5,6Hemorrhages caused by ruptured arteries are most common among young men, with greatest incidence in arteries of the abdominal cavity, followed by the popliteal artery. 5Patients with asymptomatic complications are treated conservatively.Patients with active bleeding require emergency surgery or endovascular embolization.
A bibliographic search conducted on PubMed did not identify any similar case reports involving Ehlers-Danlos type VI, but 11 related published articles were identified.
Freeman et al. 6 reviewed case reports published between January 1975 and July 1995, totaling 45 cases of vascular complications related to Ehlers-Danlos Syndrome type VI.8][9] Arteriography involves a high risk of hemorrhage, dissection, pseudoaneurysm and arteriovenous fistula, and so ultrasound or magnetic resonance angiography should be preferred. 5hen surgery is unavoidable, treatment should be restricted to ligature of the affected vessel, since 28 of the 45 cases covered in the review involved surgical treatment: 20 reconstructions and eight ligations.The number of deaths was 20 (30%), which was all of the 20 patients who underwent reconstruction.The morbidity and mortality rates of invasive imaging exams were 5% to 16%. 5    The literature does not contain clinical medical reports that could provide a basis for definition of standard treatment, because of the low incidence of this disease and its high mortality rate.Theoretically, the treatment of choice would appear to be endovascular, because it is less aggressive, but it can also have fatal results linked to difficulties controlling the location of catheterization and to arteries ruptured by balloon angioplasty or stent techniques. 51][12][13] They also recommend clinical treatment, such as control of arterial blood pressure, to reduce the risk of rupture and, if necessary, beta blockers to prevent expansion of arteries.High impact exercise such as gymnastics and long distance running should be avoided.Genetic counseling is also part of care.Identification and early diagnosis are indispensable to minimize complications, improving patients' quality of life.

Figure 1 .
Figure 1.Arterial Doppler ultrasound of the left lower limb.

Figure 2 .
Figure 2. Arteriography of the left lower limb.

Figure 3 .
Figure 3. Patient in ventral position, showing location of Z-shaped incision in the popliteal fossa.

Figure 5 .
Figure 5. Fragility of the popliteal artery wall.