: We report the case of a 10-year-old boy with hereditary hemorrhagic telangiectasia (HHT) and a family history of SMAD4-related juvenile polyposis syndrome (JPS), presenting with hypoferritinaemia unresponsive to oral supplementation. Endoscopic evaluation revealed multiple gastrointestinal polyps, including duodenal, gastric, and colonic lesions. Histology confirmed a tubular adenoma with low-grade dysplasia. Genetic analysis identified a heterozygous pathogenic SMAD4 variant (c.1549_1550del), confirming the diagnosis of JPS. This case illustrates the early onset and clinical complexity of SMAD4-associated JPS-HHT overlap syndrome. It highlights the need for earlier, individualized screening in at-risk children. Timely diagnosis and endoscopic monitoring can prevent severe complications, reduce the need for major surgery, and improve outcomes. Emerging therapies, such as Sirolimus, may offer additional benefit in managing polyp burden and anemia. Familial cascade testing was pivotal in identifying the mutation and guiding management. This report reinforces the importance of early personalized surveillance and a multidisciplinary approach in children with SMAD4 mutations.
Juvenile polyposis in a SMAD4-mutated child: A call for early surveillance
Lorusso, Claudia;Lassandro, Giuseppe;Palladino, Valentina;la Grasta, Giovanni;Dargenio, Vanessa Nadia;Giordano, Paola;Cristofori, Fernanda;Francavilla, Ruggiero
2026-01-01
Abstract
: We report the case of a 10-year-old boy with hereditary hemorrhagic telangiectasia (HHT) and a family history of SMAD4-related juvenile polyposis syndrome (JPS), presenting with hypoferritinaemia unresponsive to oral supplementation. Endoscopic evaluation revealed multiple gastrointestinal polyps, including duodenal, gastric, and colonic lesions. Histology confirmed a tubular adenoma with low-grade dysplasia. Genetic analysis identified a heterozygous pathogenic SMAD4 variant (c.1549_1550del), confirming the diagnosis of JPS. This case illustrates the early onset and clinical complexity of SMAD4-associated JPS-HHT overlap syndrome. It highlights the need for earlier, individualized screening in at-risk children. Timely diagnosis and endoscopic monitoring can prevent severe complications, reduce the need for major surgery, and improve outcomes. Emerging therapies, such as Sirolimus, may offer additional benefit in managing polyp burden and anemia. Familial cascade testing was pivotal in identifying the mutation and guiding management. This report reinforces the importance of early personalized surveillance and a multidisciplinary approach in children with SMAD4 mutations.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
