Juvenile Idiopathic Arthritis Associated with Combined JP–HHT Syndrome: A Novel Phenotype Associated with a Novel Variant in SMAD4

Abstract

Juvenile polyposis (JP) syndrome is characterized by multiple hamartomatous polyps of the gastrointestinal tract. Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia characterized by telangiectasia in the skin, mucous membranes, and arteriovenous malformations in other organs. Individuals with JP–HHT syndrome have variable features of both rare disorders, attributed to heterozygous mutations in the SMAD4 gene. Systemic juvenile idiopathic arthritis (JIA) is a severe, chronic disease marked by arthritis and systemic inflammation for which the cause remains unknown. JIA has never been described in association with SMAD4-related disease. We describe a case of JP–HHT syndrome with a novel SMAD4 variant, c.1052A > T (p.D351V), in which the child also had JIA manifestation.

Keywords

SMAD4 - juvenile polyposis syndrome - hereditary hemorrhagic telangiectasia - juvenile idiopathic arthritis - TGF-β

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