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

Juliet Chhay Bishop; Jacquelyn Francis Britton; Anne M Murphy; Sangeeta Sule; Sally Mitchell; Clifford Takemoto; Joseph M Collaco; Wikrom Karnsakul; Carmelo Cuffari; Edith Dietz; Joann Bodurtha

doi:10.1055/s-0037-1609060

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

J Pediatr Genet. 2018 Jun;7(2):78-82. doi: 10.1055/s-0037-1609060. Epub 2017 Dec 29.

Authors

Affiliations

¹ Department of Medical Genetics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
² Division of Cardiology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
³ Department of Pediatric Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
⁴ Department of Interventional Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
⁵ Department of Pediatric Hematology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
⁶ Department of Pediatric Pulmonology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
⁷ Department of Pediatric Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
⁸ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.

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; TGF-β; hereditary hemorrhagic telangiectasia; juvenile idiopathic arthritis; juvenile polyposis syndrome.

Publication types

Case Reports

Grants and funding

T32 GM007471/GM/NIGMS NIH HHS/United States