Pediatric Osler-Weber-Rendu Syndrome Workup

These tests should be ordered in coordination with a physician and genetic counselor. At specific centers and laboratories, genetic tests are available for various mutations in the endoglin gene found on chromosome 9 and the activin receptorlike kinase gene found on chromosome 12. These tests should be ordered in coordination with a physician and genetic counselor.

Currently, no laboratory studies are widely available to confirm the diagnosis of Osler-Weber-Rendu syndrome. However, certain laboratory tests may be helpful in identifying specific complications.

Because of the prevalence of arteriovenous malformations (AVMs) and associated sequelae, screening tests using multiple imaging modalities have become the standard of care for patients with Osler-Weber-Rendu syndrome. Some centers also screen asymptomatic children with a family history of Osler-Weber-Rendu syndrome in an effort to reduce serious complications associated with AVMs.

Hemoglobin may be decreased because of chronic bleeding and iron deficiency anemia, or the patient may be polycythemic because of chronic hypoxemia from a right-to-left shunt.

The platelet count may be normal or slightly increased. The WBC count should be within the reference range unless an infectious complication, such as a brain abscess, is present.

Prothrombin time and activated partial thromboplastin time values should be normal, unless severe liver involvement is present. A preliminary study also points to the usefulness of factor VIII antigen levels; elevated levels may influence thrombotic risk in Osler-Weber-Rendu syndrome.^[9]

If a right-to-left shunt is present, the arterial partial pressure of oxygen (PO₂) is low. Measurement of the arterial PO₂ while the patient is on 100% oxygen (ie, a hyperoxic test) can be used if a shunt is suspected; only a minor increase in the arterial PO₂ while the patient is on 100% oxygen confirms the diagnosis of a right-to-left shunt. In the absence of a shunt, the arterial PO₂ should increase to a much larger extent.

Screening with a hyperoxic test is shown to have 100% sensitivity and 40% specificity for the detection of pulmonary arteriovenous malformations (AVMs) in patients with Osler-Weber-Rendu syndrome who are suspected of having an AVM.

Chest radiography followed by agitated saline solution transthoracic contrast echocardiography (TTCE) with grading is now recommended as the screening test of choice for pulmonary AVMs in patients with Osler-Weber-Rendu syndrome. Initial studies of this modality suggest that its sensitivity is superior to that of computed tomography; however, because long-term follow-up data are not currently available, all patients with even low-grade evidence of pulmonary pathology on TTCE require CT imaging as a confirmatory study.

On chest radiography, pulmonary AVMs appear as a peripheral noncalcified coin lesion attached by vascular strands to the hilus.

CT scanning may be used to better delineate AVMs of the lung or head. It may also reveal larger brain abscesses.

MRI scanning is the primary screening modality for cerebral AVMs as well as telangiectasias in the CNS.

Doppler ultrasonography of the liver may be used for screening and first-line imaging in patients with Osler-Weber-Rendu syndrome for hepatic AVM and other associated sequelae.

Angiography is used to map the exact extent of the vascular lesions, usually when surgery is contemplated.

Colonoscopy reveals GI telangiectasias as small well-defined lesions surrounded by an anemic halo. Videocapsule endoscopy may be used because it often reveals telangiectasias unnoticed in the GI tract in patients with unknown sources of bleeding.^[10]

Currently, prenatal diagnosis is rarely used in families affected by Osler-Weber-Rendu syndrome. These families are encouraged to have DNA diagnosis of affected individuals where available. If the specific mutation within the family is revealed, cord blood from neonates may be analyzed for presence of the disease, and multiple screening modalities for AVMs may be used.

Biopsies of affected areas of the skin reveal focal dilatations of postcapillary venules in the dermal upper-horizontal plexus. Abnormal stress fibers are present in the venule pericytes. These findings vary from other forms of hereditary telangiectasia. Liver biopsies in patients with significant liver involvement often reveal pseudocirrhosis due to shunting from the hepatic artery to the hepatic vein or shunting from the hepatic artery to the portal vein.