Hereditary hemorrhagic telangiectasia: An overview of diagnosis and management in the molecular era for clinicians

Abstract

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) is a relatively common, underdiagnosed autosomal-dominant disorder of arteriovenous malformations and telangiectases. DNA testing for hereditary hemorrhagic telangiectasia has recently become available in North America, making presymptomatic screening available to relatives with a positive molecular diagnosis. This now enables practitioners to prevent catastrophic complications of undiagnosed pulmonary and CNS arteriovenous malformations and eliminates the need to radiographically screen all at-risk relatives shown to be unaffected by molecular testing. We review the clinical aspects of hereditary hemorrhagic telangiectasia, describe the indications, benefits, and limitations of molecular diagnostic testing for hereditary hemorrhagic telangiectasia, and provide a molecular genetics summary to facilitate genetic counseling before and after DNA testing for this complex disorder. Genet Med 2004:6(4): [175][176][177][178][179][180][181][182][183][184][185][186][187][188][189][190][191].

DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population

“…Ten different mutations, all consisting in 1-bp substitutions, were undetectable by SSCP analysis. This suggests that DHPLC is particularly suitable for detecting ALK1 mutations, since 1-bp substitutions account for 89 of the 131 ALK1 mutations reported thus far (Bayrak-Toydemir et al, 2004;Brusgaard et al, 2004;Letteboer et al, 2005;Abdalla et al, 2005;Kuehl et al, 2005;Schulte et al, 2005). The detection rate for transitions and transversions were similar with the two methods.…”

Anesthetic implications for the parturient with hereditary hemorrhagic telangiectasia

“…4 Although the specific mutation influences the extremely variable phenotypic presentation of the disease, the diversity of clinical presentations within a family suggests that other epigenetic factors or modifying genes have a role. 5 Historically, the disorder was described as a clinical triad of recurrent epistaxis, mucocutaneous telangiectasia, and a positive family history. International consensus criteria (the Curaçao criteria) for diagnosis have now been formulated.…”

“…However, they may develop in any system and have been described in the spinal, coronary, renal, splenic, ocular, uterine, and vaginal circulatory systems. 5,7 Management of patients with HHT includes screening for AVMs, correction of vascular anomalies, where possible, and management of complications as they occur. Such management is usually undertaken at specialist units where screening-surveillance recommendations have been published, particularly when pregnancy is being considered or confirmed.…”

“…25,[31][32][33][34] Spinal AVMs Spinal AVMs (SAVMs) affect up to 1% of patients with HHT. 5 Rupture of SAVMs is uncommon, and most patients present with a gradual onset of symptoms ranging from neck or back pain, to nerve root pain, to focal sensory and motor neurology, to disturbance of defecation and micturition. 37 Pregnancy exacerbates symptoms, and reports of SAVM regression postpartum have been reported.…”

“…Hepatic AVMs (HAVMs) may occur in up to 30% of HHT patients, and are more prevalent in women. 1,5 Up to 50% of HAVMs are thought to be clinically silent, but they can cause a large left to right shunt and present with high output heart failure, portal hypertension, portosystemic encephalopathy, or biliary disease. 5,40 Hereditary hemorrhagic telangiectasia may cause liver fibrosis and cirrhosis.…”