Sack–Barabas syndrome

Overview

Sack–Barabas syndrome is an outdated name for what is now classified as the vascular type of Ehlers–Danlos syndrome (vEDS), a rare and severe connective tissue disorder. It is characterized by fragile blood vessels, thin translucent skin, and a high risk of spontaneous arterial or organ rupture. The syndrome was originally described by Sack and Barabas in 1968 and has since been recognized as one of the most life-threatening subtypes of the Ehlers–Danlos syndrome spectrum.

The disorder affects the body’s collagen, particularly type III collagen, which plays a critical role in the structural integrity of blood vessels and internal organs. As a result, individuals with this condition are at risk of life-threatening complications such as arterial aneurysms, dissections, and ruptures, often occurring without warning. Although rare, vEDS demands prompt recognition and lifelong management to reduce the risk of catastrophic events.

Causes

Sack–Barabas syndrome (vascular Ehlers–Danlos syndrome) is caused by mutations in the COL3A1 gene, which encodes type III procollagen. This protein is essential for the structural strength of blood vessels, hollow organs (such as the intestines and uterus), and skin. Mutations in this gene result in defective or insufficient type III collagen, leading to increased tissue fragility.

The condition is inherited in an autosomal dominant manner, meaning a mutation in one copy of the gene is sufficient to cause the disorder. Most affected individuals inherit the condition from an affected parent, but about 50% of cases result from de novo (new) mutations with no previous family history.

Symptoms

The clinical presentation of Sack–Barabas syndrome varies in severity but typically includes the following features:

• Arterial fragility: Aneurysms, dissections, and ruptures of large and medium-sized arteries, often spontaneous and life-threatening

• Thin, translucent skin: Especially noticeable over the chest and abdomen, with visible veins

• Easy bruising: Bruises may occur with minimal or no trauma

• Facial features: A characteristic appearance that may include a thin nose, prominent eyes, small chin, and lobeless ears

• Joint hypermobility: Usually limited to small joints such as fingers and toes

• Organ rupture: Spontaneous rupture of the bowel (especially the sigmoid colon), uterus (during pregnancy or labor), and lungs (causing pneumothorax)

These symptoms often become more apparent in late adolescence or early adulthood, and severe complications can arise at any age.

Diagnosis

Early and accurate diagnosis of Sack–Barabas syndrome is essential to prevent potentially fatal events. The diagnostic process includes:

• Clinical evaluation: Assessment of family history, physical signs (thin skin, characteristic facial features, easy bruising), and history of arterial or organ rupture

• Genetic testing: Confirmation through identification of a mutation in the COL3A1 gene

• Imaging studies: CT angiography or MR angiography may be used to screen for arterial abnormalities, aneurysms, or dissections

• Skin biopsy (in select cases): May show abnormalities in collagen fibrils, but is not commonly used for diagnosis when genetic testing is available

Genetic counseling is recommended for affected individuals and family members, especially before planning a pregnancy.

Treatment

There is no cure for Sack–Barabas syndrome, and treatment focuses on risk reduction, early detection of complications, and supportive care. Management strategies include:

• Regular monitoring: Periodic vascular imaging to detect aneurysms or dissections before rupture

• Medication: Beta-blockers like celiprolol may reduce arterial stress and the risk of rupture in some patients

• Avoidance of trauma: Patients are advised to avoid contact sports, heavy lifting, and activities that increase vascular strain

• Surgical precautions: Surgery is approached cautiously due to tissue fragility. Non-invasive procedures are preferred whenever possible

• Emergency planning: Patients should carry medical alert identification and have emergency plans in place for vascular events

• Pregnancy management: High-risk pregnancy care is essential, as pregnancy increases the risk of uterine rupture and arterial complications

Prognosis

The prognosis for individuals with Sack–Barabas syndrome (vEDS) is guarded due to the high risk of life-threatening complications, particularly arterial and organ rupture. The median life expectancy is significantly reduced, often estimated to be in the range of 40 to 50 years, although some individuals live longer with vigilant medical care and risk management.

Proactive monitoring, lifestyle modification, and early treatment of vascular complications can improve quality of life and survival. Ongoing research into gene therapies and targeted treatments may offer hope for future advances in the management of this challenging condition.