High importance
Aug 26, 2026
To clarify genetic diagnoses in patients presenting with symptoms resembling hereditary hemorrhagic telangiectasia - juvenile polyposis syndrome (HHT-JPS) versus familial adenomatous polyposis (FAP).
Analysis through molecular genetic testing for SMAD4 variants in a case of a 26-year-old woman with pulmonary arteriovenous malformations and associated family history of gastrointestinal polyps.
Identification of a pathogenic SMAD4 variant confirmed the diagnosis of HHT-JPS in the patient, revealing that other family members previously diagnosed with FAP also carried this variant, necessitating re-evaluation of their diagnoses and management.
The study is based on a single case and therefore may not capture the full spectrum of phenotypic and genetic diversity present in HHT-JPS and FAP, limiting broader applicability of findings.
This distinction is crucial for proper patient management, as HHT-JPS involves different clinical considerations and interventions compared to FAP, underscoring the role of genetic testing in guiding patient care and family counseling.
A 26-year-old woman was diagnosed with hereditary hemorrhagic telangiectasia - juvenile polyposis syndrome (HHT-JPS) after an incidental finding of a pulmonary arteriovenous malformation. Molecular genetic testing confirmed the presence of a pathogenic SMAD4 variant, later found to be present in several other family members who were all previously labelled as having familial adenomatous polyposis. This short report contrasts and compares the conditions and highlights the importance of using genetic testing to distinguish similar presentations of gastrointestinal polyps in association with genetic conditions such as HHT-JPS and FAP. We highlight that detection of SMAD4 mutations can distinguish individuals with HHT-JPS from those with FAP who do not appear to present with arteriovenous malformations or notable criteria for HHT. This distinction may have significant implications for those with a longstanding familial diagnosis of FAP, as HHT-JPS entails different management considerations.