scholarly journals A novel germline BMPR1A variant (c.72_73delGA) in a Japanese family with hereditary mixed polyposis syndrome

2020 ◽  
Vol 50 (7) ◽  
pp. 826-829
Author(s):  
Yosuke Miyahara ◽  
Hideyuki Ishida ◽  
Koichi Kawabe ◽  
Hiroyuki Eto ◽  
Toyotaka Kasai ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Autosomal Dominant ◽  
Hyperplastic Polyps ◽  
Autosomal Dominant Disorder ◽  
Polyposis Syndrome ◽  
Japanese Family ◽  
Germline Variant ◽  
Juvenile Polyps ◽  
Increased Risk ◽  
Cancer Syndromes

Abstract Hereditary mixed polyposis syndrome (HMPS) is a rare autosomal dominant disorder characterized by a mixture of typical and/or atypical juvenile polyps, adenomas and hyperplastic polyps, resulting in an increased risk of colorectal cancer. In HMPS, four different germline BMPR1A variants from five unrelated families have been reported. This study is the first to report HMPS within a Japanese family. The proband underwent repeated colonoscopic polypectomies over a 5-year period, since the age of 67. Histological examination of these resected polyps revealed adenomas, juvenile-like polyps and hyperplastic changes. Genetic testing was conducted to identify the causative genes for hereditary gastrointestinal cancer syndromes, including BMPR1A. We detected a germline variant, c.72_73delGA, in BMPR1A. The proband’s elder brother, younger sister and nephew have also undergone repeated colonoscopic polypectomies at other clinics. His sister and nephew underwent genetic testing, and the same BMPR1A variant was identified.

scholarly journals Nonfamilial Juvenile Polyposis Syndrome with Exon 5 Novel Mutation in SMAD 4 Gene

2017 ◽  
Vol 2017 ◽  
pp. 1-3 ◽  
Author(s):  
Amna Ahmed ◽  
Badr Alsaleem
Keyword(s):  
Colorectal Cancer ◽  
Genetic Screening ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Juvenile Polyposis ◽  
Entire Colon ◽  
Juvenile Polyposis Syndrome ◽  
Polyposis Syndrome ◽  
Juvenile Polyps ◽  
Increased Risk

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary disorder, characterized by multiple juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. JPS is most frequently caused by mutations in the SMAD4 or BMPR1A genes. Herein, we report a child with juvenile polyposis syndrome (JPS) with a novel mutation in the SMAD4 gene. An 8-year-old boy presented with recurrent rectal bleeding and was found to have multiple polyps in the entire colon. The histology of the resected polyps was consistent with juvenile polyps. Subsequent genetic screening revealed a novel mutation in SMAD4, exon 5 (p.Ser144Stop). To the best of our knowledge, this mutation has not been reported before. Offering genotypic diagnosis for patients with JPS is an important step for strategic plan of management.

scholarly journals Diagnosis of hereditary hemorrhagic telangiectasia in a pediatric patient admitted with diabetes: the utility of genetic testing

2021 ◽  
Vol 2 (3) ◽  
pp. 01-02
Author(s):  
Alvaro E. Galvis ◽  
Beatrice Batoczki ◽  
Iris S. Pecson ◽  
Evan Vidal ◽  
Craig T. Nakamura
Keyword(s):  
Genetic Testing ◽  
Pediatric Patient ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Autosomal Dominant ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Autosomal Dominant Disorder ◽  
Case Presentation ◽  
History Of ◽  
Vascular Dysplasia

Background: Hereditary hemorrhagic telangiectasia (HHT) formerly known as Osler-Weber-Rendu syndrome is a rare autosomal dominant disorder characterized by vascular dysplasia and a wide spectrum of clinical manifestations. Case presentation: We report the case of an undiagnosed pediatric patient who presented hypoxemia on clinical exam as the only suggestive feature for the presence of HHT. Conclusions: Although HHT diagnosis is based on the finding of characteristic clinical features genetic testing should also be implemented when a family history of the disease is present to help confirm or refute the diagnosis.

scholarly journals NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020

2020 ◽  
Vol 18 (4) ◽  
pp. 380-391 ◽  
Author(s):  
Mary B. Daly ◽  
Robert Pilarski ◽  
Matthew B. Yurgelun ◽  
Michael P. Berry ◽  
Saundra S. Buys ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Genetic Testing ◽  
High Risk ◽  
Nccn Guidelines ◽  
Therapy Decision ◽  
Increased Risk ◽  
Management Recommendations ◽  
Cancer Syndromes ◽  
Familial High Risk ◽  
Testing And Counseling

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic provide recommendations for genetic testing and counseling for hereditary cancer syndromes, and risk management recommendations for patients who are diagnosed with syndromes associated with an increased risk of these cancers. The NCCN panel meets at least annually to review comments, examine relevant new data, and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panel’s discussion and most recent recommendations regarding criteria for high-penetrance genes associated with breast and ovarian cancer beyond BRCA1/2, pancreas screening and genes associated with pancreatic cancer, genetic testing for the purpose of systemic therapy decision-making, and testing for people with Ashkenazi Jewish ancestry.

Real-world outcomes of genetic testing in a GU genetics clinic and evaluation of current guidelines.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 668-668
Author(s):  
Annelise Pace ◽  
Ashley Henriksen Woodson ◽  
Rebecca Slack-Tidwell ◽  
Molly S. Daniels ◽  
Patrick Glen Pilie ◽  
...  
Keyword(s):  
At Risk ◽  
Genetic Testing ◽  
Retrospective Chart Review ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Clinical Criteria ◽  
Increased Risk ◽  
Genetic Test Results ◽  
History Of ◽  
Cancer Syndromes

668 Background: Several known hereditary cancer syndromes confer an increased risk for genitourinary (GU)-related malignancies. Various guidelines indicate when to refer patients to genetic counseling for GU cancers, but there are limited data on the performance of these guidelines in clinical practice, and the association between testing outcome and clinical and familial features that may delineate a heritable syndrome. The purpose of this study is to determine the most common indications for ordering genetic testing in a GU Genetics Clinic and evaluate the relationship between the indication for germline testing and outcome. Methods: An IRB-approved retrospective chart review was performed for 350 patients seen in a GU Genetics Clinic at a single comprehensive cancer center from 2014-2018. Subgroups of patients were formed based on their indication for genetic testing. Exact binomial tests were used to compare the proportion of patients with a positive (pathogenic or likely pathogenic) germline variant for those with vs. without each indication. Results: All patients had a genetic evaluation due to a personal or family history of GU cancer. The majority (324 of 350, 92.5%) were evaluated for either renal cell carcinoma (RCC) or prostate cancer (PrCa). Among patients seen for RCC-related evaluation (n = 159), 23 patients (14.5%) tested positive. Meeting published clinical criteria for a hereditary RCC syndrome significantly predicted positive testing ( P< 0.001). No other indication for testing, including RCC diagnosis ≤ 46 years, predicted for positive germline genetic test results. No positive patients were identified by age of RCC onset alone. Among patients seen for PrCa-related evaluation (n = 173), 13 (7.5%) individuals tested positive; all positive variants were in ATM or BRCA2. A single patient (1/13) was identified by metastatic PrCa status alone. Conclusions: Our data suggest current algorithms lack specificity for selecting individuals with RCC or PrCa at risk for germline mutations, and need to be revised. Evaluation of pedigrees and identifying presence of syndromic features are essential and increase the probability of identifying individuals at risk for harboring a germline mutation.

scholarly journals Schinzel-Giedion Syndrome with Congenital Megacalycosis in a Turkish Patient: Report of SETBP1 Mutation and Literature Review of the Clinical Features

2017 ◽  
Vol 2017 ◽  
pp. 1-4
Author(s):  
Ozgul Bulut ◽  
Zeynep Ince ◽  
Umut Altunoglu ◽  
Sukran Yildirim ◽  
Asuman Coban
Keyword(s):  
Literature Review ◽  
Autosomal Dominant ◽  
De Novo ◽  
Facial Dysmorphism ◽  
Multiple Congenital Anomalies ◽  
Patient Report ◽  
Autosomal Dominant Disorder ◽  
Turkish Patient ◽  
Increased Risk ◽  
Risk Of Malignancy

Schinzel-Giedion syndrome (SGS) is a rare autosomal dominant disorder that results in facial dysmorphism, multiple congenital anomalies, and an increased risk of malignancy. Recently, using exome sequencing, de novo heterozygous mutations in the SETBP1 gene have been identified in patients with SGS. Most affected individuals do not survive after childhood because of the severity of this disorder. Here, we report SETBP1 mutation confirmed by molecular analysis in a case of SGS with congenital megacalycosis.

scholarly journals Genetic Testing in a Patient With Suspected Hyperparathyroidism- Jaw Tumor Syndrome (HPT-JT)

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A195-A195
Author(s):  
Fatima M Kazi ◽  
Sobia Sadiq
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Parathyroid Adenoma ◽  
Autosomal Dominant ◽  
Genetic Counselor ◽  
Family Members ◽  
Autosomal Dominant Disorder ◽  
Suspected Appendicitis ◽  
Uterine Tumors ◽  
Hrpt2 Gene

Abstract Introduction: Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant disorder characterized by parathyroid tumors in association with fibro-osseous jaw tumors, uterine tumors and renal lesions. We present a case of suspected HPT-JT. Clinical Case: A 50-year-old female with suspected HPT-JT was referred for treatment of osteoporosis. Patient was initially diagnosed with osteosarcoma in 1980 at age 10, and underwent resection with leg amputation and chemotherapy. Around 1995, she was found to have primary hyperparathyroidism secondary to a parathyroid adenoma and underwent one gland parathyroidectomy. At age 30, she was then found to have multiple uterine tumors requiring hysterectomy. In 2017, she underwent CT abdomen for suspected appendicitis, which revealed multiple renal cysts and hepatic hemangiomas. In 2019, patient was found to have recurrent parathyroid adenoma and underwent revision parathyroidectomy. Pathology revealed hypercellular parathyroid gland consistent with adenoma. Based on constellation of symptoms, HPT-JS was suspected. Patient was referred to genetic counselor. Detailed family history revealed multiple family members affected by malignancies including melanoma, breast cancer, prostate cancer, liver cancer and two cousins with suspected MEN1. She underwent testing for hereditary hyperparathyroidism and melanoma including CDC73 gene. All genetic testing was surprisingly unrevealing. Discussion: CDC73 gene (also known as HRPT2 gene) is responsible for the pathogenesis of HPT-JT. While HPT-JT itself is a rare condition, 60% of patients affected by it, harbor the HRPT2 gene mutation. About 10–15% of these individuals are affected by parathyroid carcinoma. HRPT2 mutated parathyroid adenomas also seem to have some malignant potential. The autosomal dominant inheritance of HPT-JT makes gene testing important since it has implications for other family members and carries weight in clinical management of genetic carriers. Therefore patients with extensive personal or family history of malignancy should be followed closely. Endocrinologists should have a low threshold to refer such patients for genetic counseling and testing. However genetic testing also has its limitations and can only explain 50–75% of cases of HPT-JT syndrome. Hence, even though our patient has a negative genetic screen, the possibility of HPT-JT is not complete ruled out.

scholarly journals Abdomen agudo en un adolescente con poliposis juvenil. A propósito de un caso

2020 ◽  
Vol 50 (4) ◽  
Author(s):  
Rubén Muñoz Cedeño ◽  
Michelle Ricaurte Enriquez ◽  
Priscila Martínez Ballesteros ◽  
Viviana Paullán Sani ◽  
Gema Rodríguez Chica
Keyword(s):  
Abdominal Pain ◽  
Gastrointestinal Tract ◽  
Autosomal Dominant ◽  
Acute Abdominal Pain ◽  
Exploratory Laparotomy ◽  
Juvenile Polyposis Syndrome ◽  
Polyposis Syndrome ◽  
Juvenile Polyps ◽  
History Of ◽  
Dominant Condition

Juvenile polyposis syndrome is an autosomal-dominant condition disease characterized by multiple juvenile polyps in the gastrointestinal tract. These polyps may be present in the entire digestive tract; generally in the colon. We present the case of a 16-year-old adolescent with a history of polyps, who had had bowel resections for acute abdomen on two occasions (at 5 and 11 years of age). Endoscopic procedures were carried out, finding polyps and performing a polypectomy. After 24 hours, the patient presented proctorrhagia associated with acute abdominal pain by an obstruction, for which he was surgically intervened with an exploratory laparotomy where an intussusception was found.

A Case of Peutz-Jeghers Syndrome With Breast Cancer, Bilateral Sex Cord Tumor With Annular Tubules, and Adenoma Malignum Caused by STK11 Gene Mutation

2009 ◽  
Vol 19 (9) ◽  
pp. 1591-1594 ◽  
Author(s):  
Aine Clements ◽  
Katina Robison ◽  
Cornelius Granai ◽  
Margaret M. Steinhoff ◽  
Jennifer Scalia-Wilbur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Autosomal Dominant ◽  
Pelvic Mass ◽  
Gynecologic Malignancies ◽  
Autosomal Dominant Disorder ◽  
Stk11 Gene ◽  
Stromal Tumors ◽  
Increased Risk ◽  
Adenoma Malignum ◽  
Peutz Jeghers Syndrome

Background:Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder, and women with this syndrome are at an increased risk of developing intestinal and extraintestinal malignancies including breast and gynecologic malignancies. This case report presents a patient with PJS with a concomitant breast cancer, bilateral stromal tumors with annular tubules of the ovaries, and adenoma malignum of the cervix.Case:A 43-year-old woman presented with an advanced-stage breast cancer and a pelvic mass. The patient was treated with neoadjuvant chemotherapy followed by laparotomy with a hysterectomy and oophorectomy. Final pathologic examination revealed a concomitant breast cancer with metastasis to the ovaries, bilateral stromal tumors with annular tubules of the ovaries, and adenoma malignum of the cervix.Conclusions:Patients with PJS are at a high risk for intestinal and extraintestinal malignancies and can present with multiple concomitant malignancies.

Gastric cancer and paraneoplastic dermatomyositis as complications of an unrecognized juvenile polyposis syndrome

2019 ◽  
Vol 57 (04) ◽  
pp. 497-500
Author(s):  
Moritz Schiemer ◽  
Annette Schmitt-Graeff ◽  
Volker Brass ◽  
Peter Hasselblatt
Keyword(s):  
Gastric Cancer ◽  
Histopathological Examination ◽  
Juvenile Polyposis ◽  
Deficiency Anemia ◽  
Fundic Gland ◽  
Juvenile Polyposis Syndrome ◽  
Autosomal Dominant Disorder ◽  
Polyposis Syndrome ◽  
Hamartomatous Polyps ◽  
Increased Risk

AbstractJuvenile polyposis syndrome is a rare autosomal-dominant disorder characterized by multiple hamartomatous polyps in the gastrointestinal tract. It is associated with an increased risk of gastrointestinal cancer. We report the case of a 49-year-old woman presenting with proximal muscle weakness, weight loss, severe anemia, and melena. One year before, the diagnosis of a “fundic gland polyposis” was presumed after endoscopic evaluation for iron deficiency anemia had shown numerous polyps limited to the gastric mucosa. On admission, the diagnosis of dermatomyositis was made based on laboratory results with a marked elevated creatine kinase as well as the presence of characteristic clinical findings and muscle histology. Upper endoscopy revealed multiple pedunculated, edematous polyps in the stomach without apparent cancerous lesions intraluminally. Infiltration of the muscular layer was not detectable on endoscopic ultrasound. Histopathological examination of the polyps showed smooth outer surfaces and multiple dilated cystic glands, consistent with hamartomatous juvenile-type polyps. Magnetic resonance imaging revealed a peritoneal mass close to the greater curvature of the stomach, which was identified as a poorly differentiated adenocarcinoma by laparoscopic sampling. Immunohistochemical analysis of resected polyps was remarkable for a loss of SMAD4 expression, a finding that is very commonly observed in patients with gastric juvenile polyposis syndrome. Despite initial treatment response to glucocorticoids and chemotherapy, the patient died 5 months later due to progressive illness. Patients with gastric juvenile polyposis and SMAD4 mutations are at a high risk of developing gastric cancer; hence, early gastrectomy should be considered.

Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene

2015 ◽  
Vol 28 (7-8) ◽  
Author(s):  
Christel Tran ◽  
Vassiliky Konstantopoulou ◽  
Michelle Mecjia ◽  
Kusiel Perlman ◽  
Saadet Mercimek-Mahmutoglu ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Glutamate Dehydrogenase ◽  
Autosomal Dominant ◽  
Molecular Genetic ◽  
Heterozygous Mutation ◽  
Hyperinsulinemic Hypoglycemia ◽  
Molecular Genetic Testing ◽  
Autosomal Dominant Disorder ◽  
Activating Mutations ◽  
Multiple Episodes

AbstractHyperinsulinism-hyperammonemia syndrome (HI/HA) is a rare autosomal dominant disorder presenting with hypoglycemia and hyperammonemia. It is caused by activating mutations in theThree patients from two different centers, a 14-month-old female, a 28-year-old female (mother of the first patient) from Toronto and an unrelated 2.5-year-old male from Vienna, presented with multiple episodes of seizures associated with hypoglycemia.All patients had mild to moderate hypoglycemia, inappropriate insulin levels and mild hyperammonemia, thus suggesting a disorder of glutamate dehydrogenase (GDH). Molecular genetic testing of theWe present three new patients with GDH caused by heterozygous mutation in the

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