[A young man with intestinal polyposis and epistaxis]

Area of Science:

• Genetics
• Gastroenterology

Background:

• Germline mutations in the SMAD4 gene are associated with juvenile polyposis syndrome and hereditary haemorrhagic telangiectasia (HHT).
• Juvenile polyposis is a rare inherited disorder characterized by numerous polyps in the gastrointestinal tract.

Observation:

• A 23-year-old male with a history of colorectal juvenile polyposis presented with recurrent polyps in an ileo-anal pouch and epistaxis.
• DNA analysis identified a pathogenic SMAD4 mutation (c.1558G>T; p.(Glu520*)).
• Clinical findings and genetic results confirmed a diagnosis of hereditary haemorrhagic telangiectasia (HHT) in addition to juvenile polyposis.

Findings:

• The patient's SMAD4 mutation confirmed a genetic link between his juvenile polyposis and hereditary haemorrhagic telangiectasia (HHT).
• The identified mutation (c.1558G>T; p.(Glu520*)) is pathogenic and explains the co-occurrence of both conditions.

Implications:

• Genetic testing for SMAD4 mutations is essential for accurate subclassification of juvenile polyposis syndrome.
• Identifying SMAD4 mutations has significant implications for patient management and genetic counseling for affected families.
• This case highlights the importance of considering HHT in patients diagnosed with juvenile polyposis, especially when SMAD4 mutations are present.