A NovelSMAD4Mutation Causing Severe Juvenile Polyposis Syndrome with Protein Losing Enteropathy, Immunodeficiency, and Hereditary Haemorrhagic Telangiectasia

Abstract

Juvenile polyposis syndrome (JPS) is a rare genetic disorder characterized by juvenile polyps of the gastrointestinal tract. We present a new pathogenic mutation of the SMAD4 gene and illustrate the need for a multidisciplinary health care approach to facilitate the correct diagnosis. The patient, a 47-year-old Caucasian woman, was diagnosed with anaemia at the age of 12. During the following 30 years, she developed numerous gastrointestinal polyps. The patient underwent several operations, and suffered chronic abdominal pain, malnutrition, and multiple infections. Screening of the SMAD4 gene revealed a novel, disease-causing mutation. In 2012, the patient suffered hypoalbuminemia and a large polyp in the small bowel was found. Gamma globulin was given but the patient responded with fever and influenza-like symptoms and refused more treatment. The patient underwent surgery in 2014 and made an uneventful recovery. At follow-up two months later albumin was 38 g/L and IgG was 6.9 g/L. Accurate diagnosis is essential for medical care. For patients with complex symptomatology, often with rare diseases, this is best provided by multidisciplinary teams including representatives from clinical genetics. Patients with a SMAD4 mutation should be followed up both for JPS and haemorrhagic hereditary telangiectasia and may develop protein loosing enteropathy and immunodeficiency.

Metastatic colorectal cancer cells maintain the TGFβ program and use TGFBI to fuel angiogenesis

“…These events are thought to segregate early from late steps of CRC development, drawing a line between TGFβ tumor inhibiting and promoting roles. For example, SMAD4 mutations predispose patients with juvenile polyposis to gastrointestinal tumors 27 . Patients with high microsatellite instability CRC present multiple mutations of TGFβ signaling components and have lower TGFβ activity and longer survival times 28 .…”

Juvenile Polyp in Adults

“…The two genes which are currently associated with juvenile polyposis coli syndrome are BMPR1A and SMAD4. People with mutations of these genes have increased lifetime risk of developing multiple juvenile polyps or cancer of digestive system [19][20][21][22] .…”

A case of familial adenomatous polyposis with protein‐losing enteropathy treated by laparoscopic total colorectal resection: A literature review

“…3 A few case reports of juvenile polyposis and cap polyposis with protein-losing enteropathy were also confirmed. 4,5 These diseases have been improved by resection of the intestine with the site of protein leakage. A case of familial colorectal adenomatosis with protein leaky enteropathy has been reported.…”

“…It has been reported that 88% of patients with Cronkhite–Canada syndrome have hypoalbuminemia, and as for treatment, in addition to supportive care such as hypercaloric infusion, there have been reports that glucocorticoids have been effective, but the dosage and treatment mechanism remain unclear 3 . A few case reports of juvenile polyposis and cap polyposis with protein‐losing enteropathy were also confirmed 4,5 . These diseases have been improved by resection of the intestine with the site of protein leakage.…”