Prevalence and Incidence of Hereditary Hemorrhagic Telangiectasia
The prevalence of HHT ranges from 1 in 5,000 to 1 in 8,000 individuals in the general population, though recent genetic data suggests the true prevalence may be 2 to 12 times higher due to widespread underdiagnosis. 1, 2
Established Prevalence Estimates
Traditional epidemiological studies consistently report HHT prevalence between 1 in 5,000 to 1 in 8,000 individuals, with some variation based on geographic location 1, 3. More conservative estimates place the prevalence at 1.5 to 2 per 10,000 people 4. The European Society of Human Genetics reports the condition affects 1 in 5,000 to 8,000 people 3.
Geographic Variation in Prevalence
- Danish population studies documented a prevalence of 15.6 per 100,000 (approximately 1 in 6,400) as of 1995, which was higher than the 13.8 per 100,000 found in 1974, suggesting either improved detection or true population increase 5
- Argentine prepaid healthcare system identified a prevalence of 3.2 in 10,000 (1 in 3,125), substantially higher than traditional estimates and supporting the underdiagnosis hypothesis 6
- The American Academy of Otolaryngology notes prevalence varies from 1 in 5,000 to 1 in 18,000 depending on geographic location 1
Evidence of Underdiagnosis
Recent genetic analysis using the Genome Aggregation Database (gnomAD) calculated HHT prevalence between 2.1 in 5,000 and 11.9 in 5,000, representing 2 to 12 times higher than current clinical estimates 2. This discrepancy strongly supports that HHT is significantly underdiagnosed in clinical practice 1.
Contributing Factors to Underdiagnosis
- Variable penetrance and clinical manifestations mean not all gene carriers present with obvious symptoms, leading to missed diagnoses 1
- Delays in diagnosis are common, with many patients experiencing recurrent symptoms for years before HHT is recognized 1
- Clinician unfamiliarity with diagnostic criteria (Curaçao criteria) contributes to underrecognition 1
Incidence Data
True incidence rates (new cases per year) are not well-established in the literature, as most studies focus on prevalence rather than incidence 5. The autosomal dominant inheritance pattern means each child of an affected parent has a 50% chance of inheriting the condition 7.
Organ-Specific Prevalence
Hepatic Involvement
- Hepatic vascular malformations occur in 44-74% of HHT patients, implying a prevalence in the general non-HHT population of 1 in 7,000 to 1 in 12,500 1
- Only 8% of patients with liver involvement are symptomatic at the time of cross-sectional surveys 1
- Female predominance is marked for hepatic involvement, with male-to-female ratios ranging from 1:2 to 1:4.5 1
Pulmonary Involvement
- 70-90% of patients with pulmonary arteriovenous malformations have HHT, making HHT the predominant cause of PAVMs 1, 8
- In the general population, PAVM prevalence is 1 in 5,000, but can reach 26 to 56 per 100,000 in areas where HHT is more prevalent 1
Clinical Implications of Prevalence Data
The higher-than-expected genetic prevalence suggests HHT may exceed the threshold for classification as a rare disease 2. This has important implications:
- Increased clinical suspicion is warranted when evaluating patients with recurrent bilateral epistaxis, even without family history 1
- Screening of asymptomatic family members should be prioritized, as genetic testing identifies causative mutations in 97% of clinically definite cases 7
- Earlier diagnosis allows presymptomatic treatment of pulmonary and cerebral arteriovenous malformations, preventing life-threatening complications 7
Mortality Considerations
Patients younger than 60 years have twice the expected mortality rate, with excess mortality fully attributable to severe HHT complications including hemorrhage and arteriovenous malformation rupture 5. This underscores the critical importance of early diagnosis and comprehensive screening to reduce morbidity and mortality 7.