Juvenile polyposis in a SMAD4-mutated child: A call for early surveillance
Claudia Lorusso1, Giuseppe Lassandro1, Stefania Castellaneta1
1Interdisciplinary Department of Medicine, Pediatric Section, Children's Hospital Giovanni XXIII University of Bari Aldo Moro Bari Italy.
Insights
This case highlights early-onset SMAD4-associated juvenile polyposis syndrome (JPS) and hereditary hemorrhagic telangiectasia (HHT) overlap in a child. Early screening and multidisciplinary care are crucial for managing this complex genetic condition.
Area of Science:
- Genetics
- Pediatrics
- Gastroenterology
Background:
- Hereditary hemorrhagic telangiectasia (HHT) and juvenile polyposis syndrome (JPS) are distinct genetic disorders.
- SMAD4 gene mutations are associated with both HHT and JPS, leading to overlap syndromes.
- Early diagnosis and management are critical for preventing complications in affected children.
Purpose of the Study:
- To report a case of JPS-HHT overlap syndrome in a pediatric patient.
- To emphasize the importance of early genetic screening and surveillance in at-risk children.
- To discuss the clinical management and emerging therapies for SMAD4-associated disorders.
Main Methods:
- Case report of a 10-year-old boy with HHT and a family history of JPS.
- Clinical evaluation including hypoferritinemia and endoscopic assessment for gastrointestinal polyps.
- Histopathological examination of polyps and genetic analysis for SMAD4 pathogenic variants.
Main Results:
- The patient presented with hypoferritinemia and multiple gastrointestinal polyps.
- Genetic analysis confirmed a heterozygous pathogenic SMAD4 variant (c.1549_1550del), diagnosing JPS.
- The findings illustrate an early-onset JPS-HHT overlap syndrome.
Conclusions:
- SMAD4-associated JPS-HHT overlap syndrome can present early and with complex clinical features.
- Individualized screening and timely endoscopic monitoring are essential for at-risk children.
- A multidisciplinary approach and familial cascade testing are vital for effective management and improved outcomes.
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.
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