Curaçao Criteria for Hereditary Hemorrhagic Telangiectasia
The Curaçao criteria are four clinical diagnostic criteria for HHT: (1) spontaneous and recurrent epistaxis, (2) multiple telangiectasias at characteristic sites (lips, oral cavity, fingers, nose), (3) visceral arteriovenous malformations (pulmonary, hepatic, cerebral, spinal, or gastrointestinal), and (4) a first-degree relative with HHT—with three criteria confirming definite diagnosis, two indicating possible HHT, and fewer than two making HHT unlikely. 1, 2
Diagnostic Interpretation Algorithm
Definite HHT (3 or 4 criteria present)
- The positive predictive value of meeting three criteria is 100%, meaning genetic testing will confirm an HHT mutation in essentially all cases. 3
- Proceed directly to organ-specific screening without requiring genetic confirmation 2
- 90.3% of mutation-positive patients meet definite clinical criteria 3
Possible HHT (2 criteria present)
- Genetic testing is essential in this group, as only 32.7% will have an HHT-causing mutation. 3
- Target mutations in ENG, ACVRL1, and SMAD4 genes, which identify causative mutations in 97% of clinically definite cases 2
- If genetic testing is positive, initiate full organ screening protocols 2
Unlikely HHT (0-1 criteria present)
- The negative predictive value of an unlikely diagnosis is 97.7%, effectively ruling out HHT. 3
- Only 0.5% of mutation carriers present with fewer than two criteria 3
Detailed Criteria Specifications
Criterion 1: Epistaxis
- Must be both spontaneous (not trauma-induced) and recurrent 1, 4
- Occurs in more than 90% of adults with HHT 2
Criterion 2: Telangiectasias
- Must be multiple lesions 1
- Located at characteristic sites: lips, oral cavity, fingers, and nose 1, 5
- These lesions have age-related expression, often developing in the 5th decade of life 5
Criterion 3: Visceral Lesions
- Includes pulmonary arteriovenous malformations 1, 4
- Hepatic arteriovenous malformations (found in 44-74% of HHT patients) 1
- Cerebral or spinal arteriovenous malformations 1, 5
- Gastrointestinal telangiectasias 1, 4
Criterion 4: Family History
- Must be a first-degree relative (parent, sibling, or child) 1, 2
- The relative must meet Curaçao criteria for HHT diagnosis 1
- Given autosomal dominant inheritance, each child has 50% chance of inheriting the disease 2
Critical Clinical Pitfalls
Phenotypic variation is substantial even within families carrying the same mutation, so absence of symptoms in relatives does not exclude HHT. 6
Age-dependent penetrance means younger patients may not yet manifest all criteria—epistaxis typically appears first, followed by telangiectasias decades later. 2, 5
Gender influences hepatic involvement, with females showing 2-4.5 times higher rates of hepatic vascular malformations. 1