Novel Association of Juvenile Polyposis Syndrome With Atrial Septal Aneurysm and Patent Foramen Ovale: A Case Report

Abstract

Juvenile polyposis syndrome is an autosomal-dominant disorder characterized by the presence of hundreds of gastrointestinal polyps. The genes most commonly found are BMPR1A and SMAD4. The latter has been linked to vascular malformations and hereditary hemorrhagic telangiectasias. We present the case of a young woman diagnosed with juvenile polyposis syndrome and SMAD-4 mutation, who developed embolic strokes from an atrial septal aneurysm and patent foramen ovale. This case highlights the propensity of patients with juvenile polyposis syndrome and SMAD-4 mutations to develop atrial septal aneurysm and patent foramen ovale, and warrants appropriate cardiac workup in at-risk individuals.

BMPR1A mutation–positive juvenile polyposis syndrome and atrial septal defect: coincidence or association?

“…JPS in association with ASD has been previously reported in a 1978 case series describing four members of a family (three children aged 4, 6 and 9 years and their 30-year-old father) with JPS who were diagnosed with confirmed or suspected ASD and pulmonary stenosis, suggesting further familial predisposition 7. A 2018 case report described atrial septal aneurysm and patent foramen ovale in a patient with JPS (SMAD4 mutation) who developed embolic strokes 1. This suggests that patients with JPS and indeed BMPR1A mutation may be at risk of previously unrecognised cardiovascular complications.…”

“…JPS is a rare disorder predisposing to the development of multiple hamartomatous polyps in the GI tract and increased risk of colonic dysplasia 3 4. It is inherited in an autosomal dominant fashion, with the most commonly identified genetic defects being mutations in the BMPR1A and SMAD4 genes, cumulatively accounting for approximately 40% of patients with JPS 1. These genes are involved in TGF-beta signalling pathways, and unmutated contribute to the formation of normal colonic mucosa 2…”

“…In one retrospective review of a cohort of patients with SMAD4 mutation 7/34 (21%) patients with five different causative mutations had features of connective tissue disorder, including but not limited to valvular dysfunction, enlarged aortic root and aortic dissection 6. Abnormalities in the TGF-beta signalling pathway are also found in hereditary connective tissue disorders such as Marfan’s syndrome, which may account for this phenotype 1…”

“…Juvenile polyposis syndrome (JPS) is a rare disorder, which is inherited in an autosomal dominant fashion and which is caused by mutations in genes involved in transforming growth factor (TGF) beta signalling pathways 1 2. Patients with JPS are predisposed to the development of multiple hamartomatous polyps in the gastrointestinal (GI) tract and have an increased risk of colonic dysplasia 3 4.…”

“…Patients with JPS are predisposed to the development of multiple hamartomatous polyps in the gastrointestinal (GI) tract and have an increased risk of colonic dysplasia 3 4. JPS and its causative mutations may also be associated with a variety of congenital abnormalities and extraintestinal manifestations; and association with hereditary haemorrhagic telangiectasia (HHT) and connective tissue disorder has been reported in patients with SMAD4 mutation 1 5 6…”