Outcomes of patients with Juvenile Polyposis-Hereditary Haemorrhagic Telangiectasia caused by pathogenic SMAD4 variants in a pan-Scotland cohort.

Constitutional loss of SMAD4 function results in Juvenile Polyposis-Hereditary Haemorrhagic Telangiectasia Overlap Syndrome (JP-HHT). A retrospective multi-centre case-note review identified 28 patients with a pathogenic SMAD4 variant from 13 families across all Scottish Clinical Genetics Centres. This provided a complete clinical picture of the Scottish JP-HHT cohort. Colonic polyps were identified in 87% (23/28) and gastric polyps in 67% (12/18) of screened patients. Complication rates were high: 43% (10/23) of patients with polyps required a colectomy and 42% (5/12) required a gastrectomy. Colorectal cancer occurred in 25% (7/28) of patients, at a median age of 33 years. Pulmonary arteriovenous malformations were identified in 42% (8/19) of screened patients. 88% (23/26) and 81% (17/21) of patients exhibited JP and HHT features respectively, with 70% (14/20) demonstrating features of both conditions. We have shown that individuals with a pathogenic SMAD4 variant are all at high risk of both gastrointestinal neoplasia and HHT-related vascular complications, requiring a comprehensive screening programme.

Cronkhite-Canada syndrome with esophagus involvement and six-year follow-up: A case report.

BACKGROUND: Cronkhite-Canada syndrome (CCS) is a rare, noninherited disease characterized by gastrointestinal polyposis with diarrhea and ectodermal abnormalities. CCS polyps are distributed through the whole digestive tract, and they are common in the stomach and colon but very uncommon in the esophagus. CASE SUMMARY: Here, we present a case of a 63-year-old man with skin hyperpigmentation accompanied by diarrhea, alopecia, and loss of his fingernails. Laboratory data indicated anemia, hypoalbuminemia, hypocalcemia, hypokalemia, and positive fecal occult blood. Endoscopy showed numerous polyps scattered throughout the digestive tract, including the esophagus. He was treated with nutritional support and glucocorticoids with remission of his symptoms. CONCLUSION: Comprehensive treatment led by hormonal therapy can result in partial or full remission of clinical symptoms. Treatment should be individualized for each patient according to their therapy response. Surveillance endoscopy is necessary for assessing mucosal disease activity and detecting malignant transformation.

Clinical and Endoscopic Response to Anti-Tumor Necrosis Factor-Alpha Antibody Therapy in a Patient With Cronkhite-Canada Syndrome.

Cronkhite-Canada syndrome (CCS) is an acquired polyposis syndrome with gastrointestinal and extraintestinal manifestations. Given its rarity and lack of standard treatment, diagnosis and treatment are challenging. Steroid therapy and nutritional support are conventional treatments. There is no consensus on management of steroid-refractory cases. Here, we report the diagnosis and treatment course of a 54-year-old Asian male with CCS, whose initial treatment with prednisone 60 mg a day led to partial response and disease flare up during prednisone tapering. The use of infliximab and azathioprine led to promising remission of his symptoms.

A Case of Juvenile Polyposis Syndrome in a 13-year-old: A Case Report.

Juvenile polyposis syndrome is an autosomal dominant syndrome characterised by hamartomatous polyps in the gastrointestinal tract and has a high risk for colon carcinoma. This case explores the presentation of multiple polyps throughout the gastrointestinal tract, located in the stomach, proximal duodenum, colon, rectum and up to the anal canal. The locations and number of these polyps themselves were not typical and the histopathological studies suggested the condition to be an inflammatory fibroid polyp, which is a rare, benign and solitary neoplasm. Prompt and accurate diagnostic modality remains the keystone in the identification and management of such condition which was a limitation in this case as the patient was lost to follow up before a definitive diagnosis was made. Keywords: case reports; children; juvenile polyposis syndrome.

Cronkhite-Canada Syndrome- The first case from Pakistan: a case report.

Chronkhite-Canada Syndrome is characterised by diffuse gastrointestinal polyposis, dystrophic changes of the fingernails, cutaneous hyperpigmentation, alopecia, diarrhoea, weight loss, and abdominal pain. This disease is also associated with peripheral neuropathies and autoimmune disorders. Its association with other diseases may cause the polyps to turn into malignant tumours and worsen the condition. The first-line treatment is a combination of prednisone and mesalamine. NSAIDs and antibiotic administration is based on the symptoms and needs of patients. Here, we describe a 51-year-old male who presented to us with abdominal pain and significant weight loss. His physical examination showed dystrophic nails, alopecia and hyperpigmentation. Endoscopy and colonoscopy showed multiple polyps. His manifestations were consistent with Cronkhite-Canada syndrome. We prescribed oral corticosteroids, which improved his condition.

Gastrointestinal Bleeding in the Setting of Juvenile Polyposis Syndrome Due to SMAD4 Mutation.

A 27-year-old female presented at 13 weeks' gestation with epigastric pain and anemia requiring blood and iron transfusions but no family history of gastrointestinal malignancy. Upper endoscopy revealed a giant circumferential polyp and associated hyperplastic-appearing polyps in the proximal stomach. Biopsies revealed hyperplasia with lamina propria eosinophils. She was supported with intermittent transfusions until labor was induced at 34 weeks' gestation. Total gastrectomy was performed at seven weeks post-partum. Final pathology revealed multiple hamartomatous polyps without malignancy. Her anemia resolved postoperatively. Genetic testing revealed mutation of the SMAD4 gene and Juvenile Polyposis Syndrome. JPS is caused by germline mutations in the SMAD4 or BMPR1A genes and is characterized by hamartomatous polyps in the gastrointestinal tract. While most polyps are benign, malignant transformation can occur. One should have low threshold to send patients for genetic screening when multiple polyps are found in a young patient, even without family history.

Comprehensive treatment of Cronkhite-Canada syndrome: A case report and literature review.

INTRODUCTION: Cronkhite-Canada syndrome (CCS) is currently considered to be a non-hereditary disease, which is relatively rare clinically. It is also known as polyposis hyperpigmentation alopecia nail dystrophy syndrome, it is a syndrome characterized by gastrointestinal polyposis and ectodermal changes, the main manifestations are gastrointestinal symptoms, skin pigmentation, alopecia, and hypothyroidism. CASE PRESENTATION: In this paper, the clinical characteristics, diagnosis and treatment of a case of CCS admitted to Huanghe Sanmenxia Hospital were analyzed. In the course of treatment, traditional Chinese medicine was used, but no hormone, and the patient's clinical symptoms were greatly relieved. CONCLUSIONS: CCS is rare, there is no specific treatment, and traditional Chinese medicine may can greatly relieve the clinical symptoms of patients. However, it's still having to be verified by a large sample, multi-center, long-term treatment follow-up studies.

[A Rare Case of Cronkhite-Canada Syndrome Associated with Gastric Cancer and Gastric Outlet Obstruction].

Cronkhite-Canada syndrome(CCS)is a rare non-inherited disease characterized by gastrointestinal polyposis and ectodermal abnormalities. We report a rare case of CCS associated with gastric cancer and gastric outlet obstruction with a review of the literature. A 75-year-old man was admitted because of frequent vomiting and hypoproteinemia. He was diagnosed with CCS due to typical clinical and laboratory findings including alopecia, nail atrophy, hypoproteinemia, and typical gastrointestinal polyposis. Upper endoscopic examination also pointed out a large gastric cancer mainly located in the antrum and the reversible pyloric obstruction caused by the gastric tumor. Biopsy of the tumor revealed tubular adenocarcinoma. Computed tomography demonstrated the dilated duodenum caused by packing of the gastric tumor. 1.5 months after prednisolone therapy, he underwent total gastrectomy with complete resection of the dilated duodenal bulb. Histological examination revealed gastric cancer(pap>tub1)classified into Stage ⅢC. Postoperative course was uneventful and he moved to another hospital. To our knowledge, including the present case, there were 20 reported cases of CCS associated with gastric cancer from Japan(1979-2022). Also, 7 cases of CCS associated with gastric outlet obstruction was reported.

Juvenile polyposis syndrome: An overview.

Juvenile polyposis syndrome (JPS) is a rare precancerous condition that confers an increased risk of developing gastrointestinal cancers. The inheritance pattern is autosomal dominant. JPS should be clinically suspected when the other hamartomatous polyposis syndromes are excluded (i.e., Peutz- Jeghers and Cowden), in presence of numerous juvenile polyps in the colorectum or in other GI locations. Among the syndromic features, JPS can present with concomitant extra-intestinal manifestations, above all cutaneous manifestations such as telangiectasia, pigmented nevi, and skeletal stigmata. Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome. In JPS a cumulative risk of CRC of 39-68% has been estimated. The oncological risk justifies and imposes prevention strategies that aim at the cancer risk reduction through endoscopic screening, as recommended by international scientific societies. The aim of this review is to summarize clinical and genetic features of JPS and to elucidate the steps of the clinical management from diagnosis to surveillance.

Juvenile polyposis: Focus on less described manifestations.

Juvenile polyposis represents an heterogeneous disease as different genetic dominant backgrounds have been evidenced leading to different clinical presentations. It is associated in some patients with a different syndrome, Hereditary Hemorragic Telangiectasia, justifying a complementary and different management. Recent international recommendations help in managing this very rare disease, and this management should probably be restricted to expert centers able to take care of the multiple manifestations and risks of these patients and families. This paper will focus on the poorly known and evaluated aspects of juvenile polyposis, excluding the colonic involvement and epidemiology that are addressed in a different article of this issue.

Cronkhite-Canada Syndrome: A Case Report.

Cronkhite-Canada Syndrome is a rare disease characterised by diffuse gastrointestinal polyposis, abdominal pain, diarrhoea, cutaneous and mucosal hyperpigmentation, alopecia, and onychodystrophy. Here we report a case of a 40-year-old female with Cronkhite-Canada Syndrome, who presented with the complaints of diffuse abdominal pain, blood mixed stools, and diarrhoea associated with tenesmus. She had nausea and reduced appetite and lost 10 kgs in 3 months. She had hair fall (alopecia), atrophic changes of nails (onychodystrophy), and hyperpigmentation of the skin in fingers, tongues, and lips. Histopathological biopsy of the gastric and colonic biopsy revealed polypoid edematous mucosa and the colonic biopsies showed scattered dilated glands with inflammatory exudate and mucin. She got Entamoeba histolytica and COVID-19. She received respective antibiotics and protein diets that helped relieve the symptoms. After 4 weeks of steroids, her symptoms improved drastically. Corticosteroids, treating co-infection along with nutritional counselling can be helpful to relieve the symptoms. Keywords: alopecia; case reports; cronkhite-canada syndrome; hyperpigmentation.