polyposisHHT

PolyposisHHT is a term used in medical literature to describe an overlap syndrome in which hereditary hemorrhagic telangiectasia (HHT) coexists with gastrointestinal polyposis, most often linked to mutations in the SMAD4 gene. This overlap is sometimes referred to as HHT–juvenile polyposis (JP) overlap or SMAD4-related JP-HHT, and it highlights how two distinct heritable conditions can present together in a single patient.

Genetics and pathogenesis

PolyposisHHT is typically caused by germline mutations in SMAD4, a gene encoding a mediator of TGF-beta signaling. SMAD4 mutations can produce both juvenile polyposis and features of HHT, with autosomal dominant inheritance. The penetrance and expressivity vary, so individuals may show polyps, epistaxis and mucocutaneous telangiectasias, or only a subset of these features. While classic HHT is most commonly due to ENG or ACVRL1 mutations, the overlap syndrome specifically implicates SMAD4.

Clinical features

Patients may exhibit epistaxis and mucocutaneous telangiectasias typical of HHT, along with multiple hamartomatous GI polyps characteristic of juvenile polyposis. GI polyps can cause bleeding, anemia, or obstruction, and there may be an increased lifetime risk of GI malignancy in JP-HHT overlap. Extra-gastrointestinal HHT manifestations—such as arteriovenous malformations in the lungs, liver, or brain—may also be present, contributing to progressive morbidity.

Diagnosis

Diagnosis combines clinical criteria for HHT with evidence of GI polyposis and SMAD4 genetic testing. The Curaçao criteria help diagnose HHT, while endoscopic evaluation identifies polyps. Genetic testing for SMAD4 is advised when JP-HHT overlap is suspected, particularly in individuals with both polyps and HHT signs.

Management

Management is multidisciplinary. It includes control of epistaxis and mucocutaneous telangiectasias, endoscopic or surgical removal of GI polyps, and surveillance for GI bleeding and malignancy. Screening for AVMs and genetic counseling are integral parts of care.

Prognosis and epidemiology

PolyposisHHT is rare. Prognosis depends on bleeding severity, polyp-related complications, and cancer risk. Early recognition and integrated care improve outcomes, with ongoing research clarifying genotype–phenotype correlations and optimal surveillance strategies.