HHT Type 1 Clinical Characteristics and Management
Genetic Basis and Pathophysiology
- HHT type 1 results from mutations in the endoglin (ENG) gene, which encodes a transmembrane protein involved in the transforming growth factor-β (TGF-β) signaling pathway expressed on vascular endothelium 3, 2
Clinical Phenotype Distinguishing HHT1 from HHT2
- Symptoms typically appear around age 30, with epistaxis starting at mean age 11 years 2
- Pulmonary arteriovenous malformations (PAVMs) are more frequent and larger in size in HHT1 compared to HHT2 1
- Cerebral arteriovenous malformations occur more commonly in HHT1 patients 1
- Hepatic vascular malformations are less common in HHT1 compared to HHT2 1, 3
Diagnostic Approach
- Clinical diagnosis uses the Curaçao criteria requiring 3 of 4 features: spontaneous/recurrent epistaxis, multiple telangiectasias at characteristic sites, visceral lesions (PAVMs, cerebral AVMs, hepatic AVMs, GI telangiectasias), and first-degree relative with HHT 2
- Genetic testing identifies ENG mutations in 54% of HHT families and should include simultaneous sequencing and deletion/duplication analysis to detect approximately 96% of mutations 2
Screening Requirements for HHT1
- Pulmonary screening: All HHT1 patients require screening for PAVMs using contrast echocardiography or chest CT, as these can be treated presymptomatically to prevent life-threatening complications including stroke and cerebral abscess 1, 2
- Cerebral screening: MRI of the brain is recommended to detect cerebral vascular malformations given their higher frequency in HHT1 2
- Liver screening: Doppler ultrasonography as first-line imaging, though hepatic involvement is less common in HHT1 than HHT2 3, 2
- Critical caveat: Liver biopsy must be strictly avoided in any patient with proven or suspected HHT due to high hemorrhage risk 3, 2