Faculty development participants' experiences of working with change in clinical settings.

OBJECTIVES: Many universities offer faculty development to support teachers in developing and improving clinical education in the health professions. Although research shows outcomes on individual levels after faculty development, little is known about its contribution to change within the organisation. To advance current faculty development and ensure that it can support wider educational change in healthcare organisations, a better understanding of educational change practices in these settings is needed. This study therefore explores the experiences of working with educational change in clinical workplaces from the perspective of clinical educators that have undergone faculty development training. The study adopts perspectives on change as influenced by context to include the impact from clinical workplaces on individuals' change work. METHODS: A collective case study design with a multi-institutional approach was applied and individual interviews with 14 clinical educators from two universities, one in Sweden and one in South Africa, were conducted. Data were analysed separately before a cross-case analysis was performed, synthesising the findings from both sites. FINDINGS: Participants shared experiences of having limited opportunities to work with educational change beyond their own individual teaching practices within their clinical workplaces. Also, participants appeared to refrain from leading change and rather pursued change on their own or relied on indirect approaches to change. They described several workplace aspects influencing their work, including the organisation and management of teaching, the resources and incentives for teaching and the attitudes and beliefs about teaching within the clinical community. CONCLUSIONS: The study shows that clinical educators are part of communities and contexts that shape their approaches to educational change and influence which changes are feasible and which ones are not. It thus adds to the understanding of change as contextual and dynamic and contributes with implications for how to advance faculty development to better support change in practice.

Unraveling mucolipidosis type III gamma through whole genome sequencing in late-onset retinitis pigmentosa: a case report.

BACKGROUND: We describe the case of a 47-year-old man referred to a retinal clinic and diagnosed with late-onset retinitis pigmentosa. Surprisingly, genetic testing revealed compound heterozygous pathogenic variants in GNPTG, leading to the diagnosis of the autosomal recessive lysosomal storage disorder mucolipidosis type III gamma. Mucolipidosis type III gamma is typically diagnosed during childhood due to symptoms relating to skeletal dysplasia. Retinal dystrophy is not a common phenotypic feature. CASE PRESENTATION: Ophthalmologic examination was consistent with a mild form of retinitis pigmentosa and included fundus photography, measurement of best-corrected visual acuity, optical coherence tomography, electroretinogram and visual field testing. Extraocular findings included joint restriction and pains from an early age leading to bilateral hip replacement by age 30, aortic insufficiency, and hypertension. Genetic analysis was performed by whole genome sequencing filtered for a gene panel of 325 genes associated with retinal disease. Two compound heterozygous pathogenic variants were identified in GNPTG, c.347_349del and c.607dup. The diagnosis of mucolipidosis type III gamma was confirmed biochemically by measurement of increased activities of specific lysosomal enzymes in plasma. CONCLUSION: To our knowledge this is the first description of retinitis pigmentosa caused by compound heterozygous variants in GNPTG, providing further indications that late-onset retinal dystrophy is part of the phenotypic spectrum of mucolipidosis type III gamma.

How workplace learning is put into practice: contrasting the medical and nursing contexts from the perspective of teaching and learning regimes.

Health professions education places significant emphasis on learning in the clinical environment. While experiences of workplace learning have been extensively investigated, practices of workplace learning explored through field work have been less utilized. The theoretical framework of teaching and learning regimes acknowledges aspects of power and conflict in its consideration of what guides teachers and learners in their practice of workplace learning. This study aimed to explore practices of workplace learning in the two adjacent healthcare professions; medicine and nursing. We adopted an ethnographic qualitative design. Field observations and follow-up interviews were performed in three clinical departments and the data set comprised 12 full days of observations and 16 formal follow-up interviews. Thematic analysis was performed deductively according to the theoretical framework. Four teaching and learning regimes were found in the data. In the medical context, workplace learning was either practiced as reproduction of current practice or through stimulation of professional development. In the nursing context, workplace learning was either based on development of partnership between student and supervisor or on conditional membership in a professional community. The medical and nursing contexts demonstrated varying underpinnings and assumptions relating to teaching and learning. The respective practices of workplace learning in the medical and nursing context appear to hold substantial differences which might have implications for how we understand practices of workplace learning. We further conclude that the theoretical framework of teaching and learning regimes in this study proved useful in exploring workplace learning.

Merged testing for colorectal cancer syndromes and re-evaluation of genetic variants improve diagnostic yield: Results from a nationwide prospective cohort.

Approximately 5% of patients with colorectal cancer (CRC) have a Mendelian predisposition for the disease. Identification of the disease-causing genetic variant enables carrier testing and tailored cancer prevention within affected families. To determine the panorama and genetic variation of Mendelian CRC syndromes among referrals at the cancer genetics clinics in Sweden, 850 patients clinically selected for CRC genetic investigation were included in a prospective study that tested for all major hereditary polyposis and nonpolyposis CRC conditions. Genetically defined syndromes were diagnosed in 11% of the patients. Lynch syndrome was predominant (n = 73) followed by familial adenomatous polyposis (n = 12) and MUTYH-associated polyposis (n = 8); the latter of which two patients presented with CRC before polyposis was evident. One patient with a history of adolescent-onset CRC and polyposis had biallelic disease-causing variants diagnostic for constitutional mismatch repair deficiency syndrome. Post-study review of detected variants of unknown clinical significance (n = 129) resulted in the reclassification of variants as likely benign (n = 59) or as diagnostic for Lynch syndrome (n = 2). Our results reveal the panorama of Mendelian CRC syndromes at the cancer genetics clinics in Sweden and show that unified testing for polyposis and nonpolyposis CRC conditions as well as regular reexamination of sequence data improve the diagnostic yield.

Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability.

PURPOSE: Individuals with intellectual disability (ID) and/or neurodevelopment disorders (NDDs) are currently investigated with several different approaches in clinical genetic diagnostics. METHODS: We compared the results from 3 diagnostic pipelines in patients with ID/NDD: genome sequencing (GS) first (N = 100), GS as a secondary test (N = 129), or chromosomal microarray (CMA) with or without FMR1 analysis (N = 421). RESULTS: The diagnostic yield was 35% (GS-first), 26% (GS as a secondary test), and 11% (CMA/FMR1). Notably, the age of diagnosis was delayed by 1 year when GS was performed as a secondary test and the cost per diagnosed individual was 36% lower with GS first than with CMA/FMR1. Furthermore, 91% of those with a negative result after CMA/FMR1 analysis (338 individuals) have not yet been referred for additional genetic testing and remain undiagnosed. CONCLUSION: Our findings strongly suggest that genome analysis outperforms other testing strategies and should replace traditional CMA and FMR1 analysis as a first-line genetic test in individuals with ID/NDD. GS is a sensitive, time- and cost-effective method that results in a confirmed molecular diagnosis in 35% of all referred patients.

Room for improvement: One third of Lynch syndrome patients presenting for genetic testing in a highly specialised centre in Stockholm already have cancer.

BACKGROUND: Lynch syndrome is caused by germline mutations in the mismatch repair genes and is characterised by a familial accumulation of colorectal and other cancers. Earlier identification of Lynch syndrome patients enables surveillance and might reduce the risk of cancer. It is important to explore whether today's clinical care discovers patients with Lynch syndrome suitable for surveillance in time. This study aimed to describe what led to a diagnosis of Lynch syndrome in the cohort referred to the Hereditary Gastrointestinal Cancer Unit, Karolinska University Hospital, Solna, Sweden for gastrointestinal surveillance. METHODS: This was a descriptive study. Data from 1975 to 2018 were collected and compiled as a database. Age at diagnosis was calculated from the date when a pathogenic MMR gene mutation was confirmed, from the period June 1994-September 2018. Data were collected from patient protocols prospectively during patient consultations and medical records retrospectively. Criteria for inclusion were registration at the outpatient clinic and a confirmed mismatch repair gene mutation. RESULTS: A total of 305 patients were eligible for inclusion. Three major reasons for diagnosis were identified: 1. Predictive testing of a previously known mutation in the family (62%, mean age 37), 2. A family history of Lynch associated tumours (9%, mean age 37), 3. A diagnosis of cancer (29%, mean age 51). The proportion diagnosed due to cancer has not changed over time. CONCLUSION: A high proportion of patients (29%) were identified with Lynch syndrome after they had been diagnosed with an associated cancer, which suggests that there is significant room for improvement in the diagnosis of patients with Lynch syndrome before cancer develops.

Collaborative knotworking - transforming clinical teaching practice through faculty development.

BACKGROUND: Faculty development is important for advancing teaching practice in health professions education. However, little is known regarding how faculty development outcomes are achieved and how change in practice may happen through these activities. In this study, we explored how clinical educators integrated educational innovations, developed within a faculty development programme, into their clinical workplaces. Thus, the study seeks to widen the understanding of how change following faculty development unfolds in clinical systems. METHODS: The study was inspired by case study design and used a longitudinal faculty development programme as a case offering an opportunity to study how participants in faculty development work with change in practice. The study applied activity theory and its concept of activity systems in a thematic analysis of focus group interviews with 14 programme attendees. Participants represented two teaching hospitals, five clinical departments and five different health professions. RESULTS: We present the activity systems involved in the integration process and the contradiction that arose between them as the innovations were introduced in the workplace. The findings depict how the faculty development participants and the clinicians teaching in the workplace interacted to overcome this contradiction through iterative processes of negotiating a mandate for change, reconceptualising the innovation in response to workplace reactions, and reconciliation as temporary equilibria between the systems. CONCLUSION: The study depicts the complexities of how educational change is brought about in the workplace after faculty development. Based on our findings and the activity theoretical concept of knotworking, we suggest that these complex processes may be understood as collaborative knotworking between faculty development participants and workplace staff through which both the output from faculty development and the workplace practices are transformed. Increasing our awareness of these intricate processes is important for enhancing our ability to make faculty development reach its full potential in bringing educational change in practice.

Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement.

Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis.

Contradictions in clinical teachers' engagement in educational development: an activity theory analysis.

Many medical universities offer educational development activities to support clinical teachers in their teaching role. Research has focused on the scope and effectiveness of such activities and on why individual teachers attend. However, systemic perspectives that go beyond a focus on individual participants are scarce in the existing literature. Employing activity theory, we explored how clinical teachers' engagement in educational development was affected by the systems they act within. Three focus groups were held with clinical teachers from different professions. A thematic analysis was used to map the contradictions between the systems that the participants were part of and the manifestations of these contradictions in the system of education. In our model, clinical teachers were part of three activity systems directed by the objects of patient care, research and education respectively. Contradictions arose between these systems as their objects were not aligned. This manifested through the enacted values of the academic hospital, difficulties establishing educational discussions in the clinical workplace, the transient nature of educational employments, and impediments to developing a teacher identity. These findings offer insights into the complexities of engaging in educational development as clinical teachers' priorities interact with the practices and values of the academic hospital, suggesting that attention needs to shift from individual teachers to developing the systems in which they work.

A retrospective study of extracolonic, non-endometrial cancer in Swedish Lynch syndrome families.

BACKGROUND: Lynch Syndrome is an autosomal dominant cancer syndrome caused by pathogenic germ-line variants in one of the DNA-mismatch-repair (MMR) genes MLH1, MSH2, MSH6 or PMS2. Carriers are predisposed to colorectal and endometrial cancer, but also other cancer types. The purpose of this retrospective study was to characterize the tumour spectrum of the Swedish Lynch syndrome families. METHODS: Data were obtained from genetically verified 235 Lynch families from five of the six health care regions in Sweden. The material was stratified for gender, primary cancer, age and mutated gene and the relative proportions of specific cancer types were compared to those in the general population. RESULTS: A total of 1053 family members had 1493 cancer diagnoses of which 1011 were colorectal or endometrial cancer. Individuals with pathogenic variants in MLH1 and MSH2 comprised 78% of the cohort. Among the 482 non-colorectal/non-endometrial cancer diagnoses, MSH2 carriers demonstrated a significantly increased proportion of urinary tract, gastric, small bowel, ovarian and non-melanoma skin cancer compared to the normal population. MLH1 carriers had an elevated proportion of gastrointestinal cancers (gastric, small bowel, pancreas), while MSH6 carriers had more ovarian cancer than expected. Gastric cancer was predominantly noted in older generations. CONCLUSION: Lynch syndrome confers an increased risk for multiple cancers other than colorectal and endometrial cancer. The proportions of other cancers vary between different MMR genes, with highest frequency in MSH2-carriers. Gender and age also affect the tumour spectrum, demonstrating the importance of additional environmental and constitutional parameters in determining the predisposition for different cancer types.

To belong or not to belong: nursing students' interactions with clinical learning environments - an observational study.

BACKGROUND: Belongingness has been argued to be a prerequisite for students' learning in the clinical setting but making students feel like they belong to the workplace is a challenge. From a sociocultural perspective, workplace participatory practices is a framework that views clinical learning environments to be created in interaction between students and the workplace and hence, are dependent on them both. The aim of this study was to explore the interdependence between affordances and engagement in clinical learning environments. The research question was: How are nursing students influenced in their interactions with clinical learning environments? METHODS: An observational study with field observations and follow-up interviews was performed. The study setting comprised three academic teaching hospitals. Field observations included shadowing undergraduate nursing students during entire shifts. Fifty-five hours of field observations and ten follow-up interviews with students, supervisors and clinical managers formed the study data. A thematic approach to the analysis was taken and performed iteratively with the data collection. RESULTS: The results revealed that students strived to fill out the role they were offered in an aspirational way but that they became overwhelmed when given the responsibility of care. When students' basic values did not align with those enacted by the workplace, they were not willing to compromise their own values. Workplaces succeeded in inviting students into the community of nurses and the practice of care. Students demonstrated hesitance regarding their desire to belong to the workplace community. CONCLUSION: The results imply that the challenge for clinical education is not to increase the experience of belongingness but to maintain students' critical and reflective approach to health care practice. Additionally, results suggest students to be included as an important stakeholder in creating clinical learning environments rather than being viewed as consumer of clinical education.

Colonoscopy findings in high-risk individuals compared to an average-risk control population.

BACKGROUND AND AIMS: There is clear evidence of reduced morbidity and mortality from regular colonoscopy programs in patients with Lynch syndrome (LS). Today, also individuals with empirically increased risks of colorectal cancer (CRC) are offered colonoscopic surveillance. The aim was to compare the findings at the first screening colonoscopy in LS carriers, and individuals with an increased risk of bowel cancer due to family history of CRC with a control population. METHODS: Altogether 1397 individuals with an increased risk for CRC were divided in four risk groups: one with LS carriers and three groups with individuals with different family history of CRC. The findings were compared between the different risk groups and a control group consisting of 745 individuals from a control population who took part in a population-based colonoscopy study. RESULTS: In LS, 30% of the individuals had adenomas and 10% advanced adenomas. The corresponding figures in the other risk groups were 14-24% and 4-7%, compared with 10% and 3% in the control group. The relative risk of having adenomas and advanced adenomas was, compared to controls, significantly higher for all risk groups except the group with the lowest risk. Age was a strong predictor for adenomas and advanced adenomas in both risk individuals and controls. CONCLUSIONS: Individuals with a family history of CRC have a high prevalence and cumulative risk of adenomas and advanced adenomas, and screening is motivated also in this risk group.

Identifying keys to success in clinical learning: a study of two interprofessional learning environments.

The aim of this study was to study the intrinsic system behind interprofessional clinical learning environments. Two health care units were selected on the basis of having received a reward for best clinical learning organization. Interviews were carried out with health care staff/clinical supervisors from different professions. The interviews were transcribed and analysed according to qualitative content analysis, and categories and themes were identified. Analysis revealed two different systems of clinical learning environments. In one, the interplay between the structural aspects dominated, and in the other, the interplay between the cultural aspects dominated. An important similarity between the environments was that a defined role for students in the organization and interprofessional teamwork around supervision across professional borders was emphasized.

HTAD patient pathway: Strategy for diagnostic work-up of patients and families with (suspected) heritable thoracic aortic diseases (HTAD). A statement from the HTAD working group of VASCERN.

Heritable thoracic aortic diseases (HTAD) are rare pathologies associated with thoracic aortic aneurysms and dissection, which can be syndromic or non-syndromic. They may result from genetic defects. Associated genes identified to date are classified into those encoding components of the (a) extracellular matrix (b) TGFß pathway and (c) smooth muscle contractile mechanism. Timely diagnosis allows for prompt aortic surveillance and prophylactic surgery, hence improving life expectancy and reducing maternal complications as well as providing reassurance to family members when a diagnosis is ruled out. This document is an expert opinion reflecting strategies put forward by medical experts and patient representatives involved in the HTAD Rare Disease Working Group of VASCERN. It aims to provide a patient pathway that improves patient care by diminishing time to diagnosis, facilitating the establishment of a correct diagnosis using molecular genetics when possible, excluding the diagnosis in unaffected persons through appropriate family screening and avoiding overuse of resources. It is being recommended that patients are referred to an expert centre for further evaluation if they meet at least one of the following criteria: (1) thoracic aortic dissection (<70 years if hypertensive; all ages if non-hypertensive), (2) thoracic aortic aneurysm (all adults with Z score >3.5 or 2.5-3.5 if non-hypertensive or hypertensive and <60 years; all children with Z score >3), (3) family history of HTAD with/without a pathogenic variant in a gene linked to HTAD, (4) ectopia lentis without other obvious explanation and (5) a systemic score of >5 in adults and >3 in children. Aortic imaging primarily relies on transthoracic echocardiography with magnetic resonance imaging or computed tomography as needed. Genetic testing should be considered in those with a high suspicion of underlying genetic aortopathy. Though panels vary among centers, for patients with thoracic aortic aneurysm or dissection or systemic features these should include genes with a definitive or strong association to HTAD. Genetic cascade screening and serial aortic imaging should be considered for family screening and follow-up. In conclusion, the implementation of these strategies should help standardise the diagnostic work-up and follow-up of patients with suspected HTAD and the screening of their relatives.

Prevalence of colonic neoplasia and advanced lesions in the normal population: a prospective population-based colonoscopy study.

OBJECTIVE: There are few prospective studies of the prevalence of colonic neoplasia in the normal population. In order to properly evaluate screening-protocols for colorectal cancer in risk groups (e.g., older subjects or those with a family history), it is essential to know the prevalence of adenomas and cancer in the normal population. METHODS: A prospective population-based colonoscopy study on 745 individuals born in Sweden aged 19-70 years was conducted (mean age 51.1 years). All polyps seen were retrieved and examined. RESULTS: Out of the 745 individuals 27% had polyps, regardless of kind. Adenomas were found in 10% of the individuals and finding of adenomas was positively correlated to higher age. Men had adenomas in 15% and women in 6% of the cases. Women had a right-sided dominance of adenomas. Hyperplastic polyps were seen in 21% of the individuals. The presence of hyperplastic polyps was significantly positively correlated to the presence of adenomas. Advanced adenomas were seen in 2.8% of the study participants, but no cancers were detected. CONCLUSION: One in 10 healthy subjects had an adenoma but advanced adenomas were uncommon. Men and women have a different adenoma prevalence and localization. The results provide baseline European data for evaluating colonoscopy screening-protocols for colorectal cancer risk groups, and the findings may have implications for colon cancer screening in the normal, otherwise-healthy population.

Women with Ehlers-Danlos syndrome experience low oral health-related quality of life.

AIMS: To investigate the perceived impact of oral health-related quality of life problems in individuals with Ehlers-Danlos syndrome. METHODS: Members of the Swedish Ehlers-Danlos Syndrome Association completed the Oral Health Impact Profile (OHIP-14). Of the 250 participating individuals, 223 were women, and they were the main focus of the analyses. The results were compared with a previous study of the oral health impact on quality of life in the Swedish population. Statistical methods used for comparison were the Student t and chi-square tests. RESULTS: The mean OHIP-14 value for the entire Ehlers-Danlos syndrome group was 11.1. The mean for women was 11.8, which was significantly higher than 6.8 of the comparison group. The OHIP-14 score varied among age groups, and the highest mean value was found in the age group between 56 and 65 years of age. The most statistically significant differences between the subjects with Ehlers-Danlos syndrome and the comparison group were found for OHIP items 3, 4, and 8: "I have had pain in the mouth," "I have had discomfort when eating," and "I have been forced to interrupt meals." CONCLUSION: It is well-known that Ehlers-Danlos syndrome has a considerable impact on health-related quality of life, and this study is the first to reveal that women with Ehlers-Danlos syndrome report a low oral health-related quality of life as measured with the OHIP-14. Dimensions that were particularly relevant were physical pain, psychologic discomfort, and handicap.

Navigating Affordances for Learning in Clinical Workplaces: A Qualitative Study of General Practitioners' Continued Professional Development.

Medical specialists' lifelong learning is essential for improving patients' health. This study identifies affordances for learning general practitioners (GPs) engage in, and explores what influences engagement in those affordances. Eleven GPs were interviewed and the interview transcripts were analysed thematically. Stephen Billett's theoretical framework of workplace participatory practices was used as an analytical lens to explore the topic. Challenging patient cases were identified as the main trigger for engagement in learning. Local, national and international colleagues from the same and other specialties, were found to be an important affordance for learning, as was written material such as websites, journals and recommendations. Other inputs for learning were conferences and courses. Workplace aspects that were essential for GPs to engage in learning related to: place and time to talk, relevance to work, opportunity for different roles, organisation of work and workload, and working climate. Importantly, the study identifies a need for a holistic approach to lifelong learning, including spontaneous and structured opportunities for interaction over time with colleagues, establishment of incentives and arenas for exchange linked to peer learning, and acknowledgement of the workplace as an important place for learning and sufficient time with patients. This study contributes with a deepened understanding of how GPs navigate existing affordances for learning both within and outside their workplaces.

A retrospective two centre study of Birt-Hogg-Dubé syndrome reveals a pathogenic founder mutation in FLCN in the Swedish population.

Birt-Hogg-Dube syndrome (BHDS) (MIM: 135150) is a rare autosomal dominant disorder with variable penetrance, caused by pathogenic variants in the FLCN gene. Only a few hundreds of families have so far been described in the literature. Patients with BHDS present with three distinct symptoms: fibrofolliculomas, pneumothorax due to lung cyst formation, and increased lifetime risk of kidney tumours. The aim of the current study was to estimate the incidence of BHDS in the Swedish population and further describe the clinical manifestations and their frequency. Splice variant c.779+1G>T was the most common pathogenic variant, found in 57% of the families, suggesting this may be a founder mutation in the Swedish population. This was further investigated using haplotype analysis in 50 families that shared a common haplotype. Moreover, according to gnomAD the carrier frequency of the c.779+1G>T variant has been estimated to be 1/3265 in the Swedish population, however our data suggest that the carrier frequency in the Swedish population may be significantly higher. These findings should raise awareness among physicians of different specialties to patients presenting with fibrofolliculomas, pneumothorax and/or kidney tumours. We also stress the importance of consensus recommendations regarding diagnosis and clinical management of this, not that uncommon, syndrome.

Ovarian cancer linked to Lynch syndrome typically presents as early-onset, non-serous epithelial tumors.

OBJECTIVE: Heredity is a major cause of ovarian cancer and during recent years the contribution from germline mismatch repair (MMR) gene mutations linked to Lynch syndrome has gradually been recognized. METHODS: We characterized clinical features, tumor morphology and mismatch repair defects in all ovarian cancers identified in Swedish and Danish Lynch syndrome families. RESULTS: In total, 63 epithelial ovarian cancers developed at mean 48 (range 30-79) years of age with 47% being early stage (FIGO stage I). Histologically, endometrioid (35%) and clear cell (17%) tumors were overrepresented. The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%. Immunohistochemical loss of the corresponding MMR protein was demonstrated in 33/36 (92%) tumors analyzed. CONCLUSION: The combined data from our cohorts demonstrate that ovarian cancer associated with Lynch syndrome typically presents at young age as early-stage, non-serous tumors, which implicates that a family history of colorectal and endometrial cancer should be specifically considered in such cases.