Is This Patient Likely to Have HHT?
This patient is unlikely to have HHT based on current evidence, as she meets only 1 of 4 Curaçao criteria (possible visceral lesion) and has a variant of uncertain significance rather than a confirmed pathogenic mutation. 1
Applying the Curaçao Diagnostic Criteria
The diagnosis of HHT requires clinical assessment using the Curaçao criteria, which includes four features: 1, 2
- Spontaneous and recurrent epistaxis: Absent in this patient 1
- Multiple telangiectasias at characteristic sites (lips, oral cavity, fingers, nose): Not mentioned, presumably absent 1
- Visceral lesions (pulmonary AVMs, hepatic AVMs, cerebral AVMs, GI telangiectasias): The inferior mesenteric venous varix is NOT a typical HHT vascular malformation 1, 2
- First-degree relative with HHT: Not mentioned 1
Diagnostic classification: 1
- Definite HHT = 3 of 4 criteria
- Possible/suspected HHT = 2 of 4 criteria
- Unlikely HHT = fewer than 2 criteria
This patient has at most 1 criterion (and even that is questionable), making HHT unlikely by clinical standards. 1
The ENG Variant of Uncertain Significance
A VUS in ENG is insufficient to diagnose HHT—clinical criteria must be met. 1 The presence of an ENG variant alone does not establish disease, as: 1, 3
- VUS designation means the variant's pathogenicity is unproven 3
- Even pathogenic ENG mutations require clinical manifestations for HHT diagnosis 1
- Approximately 97% of patients with definite clinical HHT (meeting 3+ Curaçao criteria) have identifiable mutations, but the reverse is not true—genetic findings must correlate with phenotype 1, 2
The Venous Varix Is Not an HHT Lesion
The inferior mesenteric venous varix does not represent a typical HHT vascular malformation. 2, 4 HHT is characterized by: 2, 4
- Arteriovenous malformations (AVMs): Direct artery-to-vein connections bypassing the capillary bed 2, 4
- Telangiectasias: Enlarged vessels with thin walls prone to rupture 5
A venous varix is a dilated vein without arterial involvement and does not fit the pathophysiology of HHT vascular lesions. 2 This finding should not count toward the visceral lesion criterion. 1
Age and Phenotype Considerations
At age 54, this patient is well beyond the typical age of HHT manifestation: 6
- Epistaxis typically begins at mean age 11 years in HHT1 (ENG mutations) 6
- Symptoms generally appear by age 30 6
- Over 90% of adults with HHT have epistaxis 1
The complete absence of epistaxis at age 54 makes HHT highly unlikely, even with an ENG variant. 1, 6
Recommended Next Steps
Despite the low likelihood of HHT, the presence of an ENG VUS warrants: 1, 6
Detailed family history assessment for HHT features in first-degree relatives (epistaxis, telangiectasias, known HHT diagnosis) 1
Physical examination specifically looking for mucocutaneous telangiectasias on lips, tongue, oral mucosa, fingertips, and nail beds 1, 5
Genetic counseling to evaluate the ENG variant through: 3
- Review of variant databases for prior HHT associations
- Functional prediction analysis
- Segregation analysis if family members are available for testing
If family history or examination reveals additional Curaçao criteria, then proceed with organ-specific screening: 1, 6
Do NOT perform liver biopsy under any circumstances if HHT becomes suspected, due to catastrophic hemorrhage risk 1, 6
Critical Pitfall to Avoid
Never diagnose HHT based on genetic testing alone—the clinical phenotype drives diagnosis. 1 A VUS has uncertain pathogenicity by definition, and even confirmed pathogenic mutations require clinical correlation. 3 This patient's lack of epistaxis, telangiectasias, and true AVMs makes HHT diagnosis untenable regardless of genetic findings. 1, 2