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Source at https://doi.org/10.1007/s10689-018-0072-8. Familial adenomatous polyposis (FAP) is usually caused by germline mutations in the adenomatous polyposis coli (APC) gene. The classic form is characterized by hundreds to thousands of adenomas in the colorectum and early onset colorectal cancer (CRC) if left untreated. FAP is also associated with multiple extra-colonic manifestations such as gastroduodenal polyps, osteomas, epidermoid cysts, fibromas and desmoids. Most desmoid tumours in FAP patients occur intra-abdominally. Approximately 15–20% of the APC mutations are de novo mutations. Somatic mosaicism has been reported in some sporadic cases of polyposis but is probably an underestimated cause of the disease. This case report presents the detection of a mosaic APC mutation in a 26-year-old woman who as a child had been diagnosed with desmoid type fibromatosis. FAP was suggested when she presented with extensive extra abdominal fibromatosis. Our findings indicate that APC mutations may be suspected in patients presenting with a desmoid regardless of its location. If there is clinical evidence that the patient has FAP, adenomas and colonic mucosa in addition to leukocyte DNA should be included in the screening, preferably using methods that are more sensitive than Sanger sequencing.

Background Post-infectious fatigue syndrome (PIFS), also known as post-viral fatigue syndrome, is a complex condition resulting in physical, cognitive, emotional, neurological, vocational and/or role performance disabilities in varying degrees that changes over time. The needs for health care resources are high, and costly, as is the economic burden on the affected individuals. Many factors may impact the trajectory, and frequently PIFS develops into a chronic condition. Health professionals lack understanding and knowledge, which results in delayed diagnosis, lack of recognition, appropriate treatment, support and practical help. The aim of our study was to explore, from the perspective of persons who had lived with PIFS for four years following an outbreak of Giardia l. induced enteritis, factors that may have impacted their illness trajectory and how these factors had played a role during different phases. Methods In this retrospective exploratory qualitative study a group of 26 affected adults between 26 and 59 years old were selected for in-depth interviews. A maximum variation sample was recruited from a physician-diagnosed cohort of persons with PIFS enrolled at a tertiary outpatient fatigue clinic. The interviews were audio-recorded, transcribed verbatim and subjected to qualitative content analysis. Results Unhelpful and helpful factors were associated with the healthcare system, health professionals and the affected persons were experienced as having an impact on the trajectory. External impacting factors which are related to the health care system, providers and the social security system are misdiagnosis, trivialization of symptoms, unhelpful advice, delayed diagnosis and lack of appropriate help. Internal impacting factors related to the affected individuals were lack of knowledge, overestimating functional capacity, assuming the condition will pass, ignoring body signals and denial. A model of impacting factors in each phase of the trajectory is presented. Conclusion Unmet needs may result in unnecessary disability and high societal and personal costs. Enhanced knowledge of impacting factors in each phase of the trajectory may contribute to more timely and tailored health care services and less use of health services. Increased functional capacity, improved health and ability to work or study may reduce the societal costs and the economic burden for the affected individuals.

We report the 5- and 10-year survival rate of women diagnosed with breast cancer in the context of an annual MRI-based surveillance program. In 2001, as part of a national initiative, women in Norway with a BRCA1 mutation were offered annual screening with breast MRI in addition to mammography. 802 women with a BRCA1 mutation were screened one or more times and followed for a mean of 4.2 years. As of December 2011, 68 of 802 women in the screening program were diagnosed with DCIS or invasive breast cancer (8.5 %), including eight prevalent, 50 incident screen-detected and eight interval cancers. Two latent cancers were detected at prophylactic mastectomy. Sixty-three of the cancers were invasive and five were in situ. The mean tumour size was 1.4 cm (range 0.2-4.5 cm), and 85 % of the patients were node-negative. Ten of the 68 patients died of cancer in the follow-up period. The 5-year breast cancer-specific survival for women with cancer was 75 % (95 % CI 56-86 %) and the 10-year survival was 69 % (95 % CI: 48-83 %). The 5-year survival for women with Stage 1 breast cancer was 82 % compared to 98 % in the population. The 5- and 10-year survival of women with a BRCA1-associated breast cancer detected in a national MRI-based screening program in BRCA1 mutation carriers Norway was less than anticipated. The benefit of annual MRI surveillance on reducing breast cancer mortality in BRCA1 mutation carriers remains to be proven.

Endometrial cancer is frequent in MMR-mutation carriers. Estimates of annual incidence rates have, however, been based on retrospective studies. The purpose of our study was to prospectively assess the incidence rates of endometrial cancer in women either having a mutation in one of the four MMR genes MLH1, MSH2, MSH6 or PMS2 (Mut+) or belonging to families meeting the revised Amsterdam criteria in which no MMR mutation was detected (Ams+). Eight out of 80 Mut+ (10%) contracted invasive endometrial cancer compared to 1/171 (0.6%) of the Ams+ (P = 0.0006). The annual incidence rate after first control was 2.5% in Mut+ and 0.2% in Ams+. Two of the 8 Mut+ women (25%) had synchronous gynaecological tumours. The numbers included did not allow for firm conclusions, but the results are in keeping with the notion that the inherited colon-endometrial cancer syndrome may be restricted to carriers of MMR mutations.

Hereditary nonpolyposis colorectal cancer (HNPCC) may be caused by germline truncating mutations in DNA mismatch repair (MMR) genes. Whether or not missense or inframe mutations are disease-associated has become a practical clinical problem, because predictive genetic testing is employed to select high-risk persons for clinical examinations. Clinical examinations may reveal polyps to be removed and prevent cancer. One large kindred applying for health care had a N596del mutation in the MSH2 gene. The aim of this study was to determine whether or not the inframe mutation in this family was associated with disease, and to examine the tumours for presence of the MSH2 protein by immunohistochemistry. We demonstrated that the mutation was linked to disease with lod score 5.7 in the family, and all examined, but one manifest cancer, lacked the MSH2 protein.

Background and aims: Hereditary non-polyposis colorectal cancer (HNPCC) may be caused by mutations in the mismatch repair (MMR) genes MLH1, MSH2 or MSH6. Family history (Amsterdam criteria) has traditionally been used to select patients for mutation testing. It has been demonstrated that germline mutations in the MMR genes are associated with lack of the corresponding gene product as assessed with immunohistochemistry (IHC) in tumour specimens. The aim of the study was to assess the value of the Amsterdam criteria II and IHC in predicting germline mutations. Methods: Fifty-six families that were previously tested for MLH1, MSH2 and MSH6 mutations were selected for this study. All pedigrees were extended and verified and the families were scored according to the original (I) and the revised Amsterdam criteria (II). The probabilities for MLH1 and MSH2 mutations were calculated by logistic regression. In addition, all available tumour material from indexed family members was examined by IHC for the presence of the three gene products. Results: Three out of seven (39%) families where the mutation could be identified complied with the Amsterdam criteria I, while all seven (100%) met the Amsterdam criteria II. All families carrying a MLH1 or MSH2 mutation had > 15% calculated probability of finding a mutation. Tumours from all seven mutation carriers lacked the immunohistochemical expression of the corresponding MMR gene. Conclusion: The results indicate that the Amsterdam criteria II in combination with immunohistochemistry of the mismatch repair proteins in tumours may be a cost-effective approach to select families for mutation analysis.

Hereditary non-polyposis colorectal cancer (HNPCC) is a common autosomal dominant condition characterized by early onset colorectal cancer as well as other tumour types at different anatomical sites1. HNPCC tumours often display a high level of genomic instability, characterized by changes in repeat numbers of simple repetitive sequences (microsatellite instability, MSI), which reflects the malfunction of the DNA mismatch repair machinery2, 3. Accordingly, HNPCC was shown to be caused by germline mutations in the DNA mismatch repair genes (MMR) MSH2, MLH1, PMS1, PMS2 and MSH6 (refs 3, 4, 5, 6). So far, more than 220 predisposing mutations have been identified, most in MSH2 and MLH1 and in families complying with the clinical Amsterdam criteria3, 7, 8 (AMS+). Many HNPCC families, however, do not fully comply with these criteria, and in most cases the causative mutations are unknown.

THROMBOCYTOPENIC bleedings have to our knowledge not yet been described in pigs. However, purpura in adult pigs and piglets has already been described1–3, but the aetiology of these cases remains unknown and platelet counts were not performed.

THE presence of histamine in normal rumen liquor has not been proved decisively, and the part played by this substance in acute indigestion in ruminants has not been well established.