Fast Genetic Screening for Vascular EDS Crucial for Patients in Urgent Situations, Case Study Shows

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Osteogenesis Imperfecta, mutations, EDS

Fast genetic screening for vascular Ehlers-Danlos syndrome (vEDS) may be crucial in urgent situations to appropriately manage patients with severe bleeding complications, according to a recent case report.

The case was described in the study, “Peripartum Iliac Arterial Aneurysm and Rupture in a Patient with Vascular Ehlers-Danlos Syndrome Diagnosed by Next-Generation Sequencing,” published in the International Heart Journal.

Vascular EDS is a genetic disorder caused by mutations in the COL3A1 gene, which provides instructions to produce collagen type 3, a protein found in the connective tissue of the skin, lung, and vascular system. The connective tissue provides structure and support throughout the body.

This disease mainly affects blood vessels, and is characterized by easy bruising, translucent skin, and fragile blood vessels. It often appears as vascular aneurysms and vessel rupture, leading to hemorrhages.

Pregnant women with vEDS have a 5.3% risk for lethal vascular complications during the peripartum period (shortly before, during, and immediately after giving birth).

Researchers in Japan reported a case of a 25-year-old pregnant woman at 34 weeks of gestation who was admitted to the hospital due to acute left abdominal pain.

She had translucent skin and a large hematoma — a solid swelling of clotted blood — on her right forearm. Her mother and older brother had no history or predisposition for bleeding or of connective tissue diseases, but her younger brother from a different father showed signs of blood vessel fragility.

The baby was delivered the same day she was admitted due to a severely low heart rate. During the procedure, the doctors identified a large hematoma on the left side of the patient’s abdominal cavity.

An analysis from a computed tomography scan confirmed the patient had an aneurism on the left common iliac artery, located in the pelvic region, with a large hematoma. Four days after the delivery, her condition worsened, and physicians found that the artery had ruptured.

At this point, clinicians started to suspect the woman had vEDS or another connective tissue disease, even in the absence of familial history.

Due to the sensitive situation of the patient, the doctors conducted an urgent genetic screening, based on next generation sequencing (NGS), for 54 genes associated with hereditary connective tissue disorders. NGS is a powerful method that enables the rapid identification of mutations in several genes simultaneously.

Despite intensive medication, the woman’s aneurism was progressively enlarging. The doctors tried to prevent its rupture through surgery, but the procedure was stopped due to her severe tissue fragility.

The results of the genetic screening, delivered two weeks after the request, revealed a COL3A1 gene mutation. Additional analysis confirmed it was disease-causative, confirming a vascular EDS diagnosis.

With this diagnosis, clinicians were able to make an informed decision about which procedure or therapy to implement to resolve the patient’s life-threatening aneurism. Due to the elevated risk of open surgery in these patients, the doctors conducted a cautious endovascular therapy — a procedure performed inside the blood vessel.

One week after the surgery and appropriate medication, the woman was discharged with no additional complications. Later on, her young brother was found to carry the same mutation and was also diagnosed with vEDS.

“This is the first report for pretreatment molecular diagnosis of vEDS using NGS [next generation sequencing] in an emergent situation in a patient with severe vascular complications,” the researchers wrote.

Based on the results, the team suggested that NGS could be “an irreplaceable piece in the management of patients with vEDS, enabling urgent, accurate, and noninvasive diagnosis expected to improve survival of those with vEDS through appropriate surveillance, prevention, and surgical intervention.”