Case report of juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome: first report in Korea with a novel mutation in the SMAD4 gene

Abstract

Juvenile polyposis/hereditary hemorrhagic telangiectasia (JPS/HHT) syndrome is a rare, autosomal dominant disorder caused by mutations in the SMAD4 gene, presenting with features of both juvenile polyposis syndrome (JPS) and HHT. Reports and studies of JPS/HHT syndrome are mostly from Western countries, while there are scarce reports from East Asian countries. We report a case of a Korean boy who had been previously diagnosed with JPS at 7 years and had first visited to our center at 15 years of age. Genetic studies of the patient and parents revealed a novel variant in the SMAD4 gene, SMAD4 c.1146_1163del; p.His382_Val387del (NM_005359.5), which had developed de novo. Numerous pedunculated and sessile polyps were observed throughout the gastrointestinal (GI) tract. Mucocutaneous telangiectases were observed on the lips, tongue, and jejunum, and arteriovenous malformations (AVMs) were observed in both lungs. This is the first case report of JPS/HHT syndrome in Korea, with a novel deletion variant in the SMAD4 gene. Patients with JPS should undergo genetic evaluation of associated genes including SMAD4, and those with genetically confirmed SMAD4 variants should undergo further evaluation for coexisting asymptomatic AVMs in order to prevent life-threatening complications of thrombotic emboli and pulmonary hemorrhage.

A neglected cause of anaemia: hereditary hemorrhagic telangiectasia

“…3 SMAD4 mutations cause juvenile polyposis overlap with HHT (JPHT). 5 HHT-1 is associated with earlier onset of the disease and has vascular malformations in the lungs and brain predominately. HHT-2 has a later onset with vascular malformations in the liver.…”

Hereditary hemorrhagic telangiectasis with juvenile polyposis syndrome: a case report

“…Kang et al . 12 reported a case in South Korea of a hereditary hemorrhagic patient with blood capillary dilation and juvenile polyposis. The patient’s frequent nose bleeding occurred at the age of 5 and JPS symptoms began at the age of 7 years; 30–50 colon polyps were observed.…”

Hereditary Hemorrhagic Telangiectasia (HHT)/Osler-Weber-Rendu Syndrome: A Review on Contemporary Knowledge, its Accompanying Clinical Manifestations, Diagnostics, and Oro-Dental Management Plan

“…In 2012, O'Malley and associates studied and determined the prevalence and clinical manifestations of HHT in their juvenile polyposis patients and concluded that nearly all have the overlap syndrome and that healthcare providers must be aware and cognizant of the juvenile polyposishemorrhagic hereditary telangiectasia overlap syndrome [10]. In 2021, the first case of JPS-HHT in South Korea was reported (a 15-year-old boy), exhibiting the performed genetic studies of the patient himself and his parents revealing the detection of a de novo variant in the SMAD4 gene, [SMAD4 c.1146_1163del; p. His382_Val387del] [12]. This report recommended that JPS patients should undergo genetic evaluation of associated genes, including SMAD4, and those patients who are genetically confirmed with SMAD4 variants ought to undergo the appropriate evaluation to detect coexisting asymptomatic AVMs and avert life-threatening complication(s) [12].…”

“…In 2021, the first case of JPS-HHT in South Korea was reported (a 15-year-old boy), exhibiting the performed genetic studies of the patient himself and his parents revealing the detection of a de novo variant in the SMAD4 gene, [SMAD4 c.1146_1163del; p. His382_Val387del] [12]. This report recommended that JPS patients should undergo genetic evaluation of associated genes, including SMAD4, and those patients who are genetically confirmed with SMAD4 variants ought to undergo the appropriate evaluation to detect coexisting asymptomatic AVMs and avert life-threatening complication(s) [12].…”