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Background Studies indicate that variants of uncertain significance are more common in non-European populations due to lack of a diversity in population databases. This difference has not been explored in epilepsy, which is increasingly found to be genetic in paediatric populations, and has precision medicine applications. This study examines the differences in the frequency of uncertain next-generation sequencing (NGS) results among a paediatric epilepsy cohort between ancestral groups historically under-represented in biomedical research (UBR) and represented in biomedical research (RBR). Methods A retrospective chart review of patients with epilepsy seen at Columbia University Irving Medical Center (CUIMC). One hundred seventy-eight cases met the following criteria: (1) visited any provider within the Pediatric Neurology Clinic at CUIMC, (2) had an ICD code indicating a diagnosis of epilepsy, (3) underwent NGS testing after March 2015 and (4) had self-reported ancestry that fit into a single dichotomous category of either historically represented or under-represented in biomedical research. Results UBR cases had significantly higher rates of uncertain results when compared with RBR cases (79.2% UBR, 20.8% RBR; p value=0.002). This finding remained true after controlling for potential confounding factors, including sex, intellectual disability or developmental delay, epilepsy type, age of onset, number of genes tested and year of testing. Conclusion Our results add to the literature that individuals who are of ancestries historically underrepresented in genetics research are more likely to receive uncertain genetic results than those of represented majority ancestral groups and establishes this finding in an epilepsy cohort. [ABSTRACT FROM AUTHOR]

Telegenetics played an important role in providing genetic services to patients during the COVID-19 pandemic. In particular, at our institution, it enabled us to expand our genetic counseling and testing services to non-local family members of patients outside of our prior catchment area. However, as telegenetics continues to be utilized even as social distancing is no longer required, further information is needed regarding the impact of this modality on patient experience within cardiogenetics. This study qualitatively explored the experiences of 12 genotype positive individuals who underwent genetic counseling and testing via telegenetics during the first 22 months of the COVID-19 pandemic and compared the experiences of local vs. non-local patients. Both local and non-local participants discussed similar benefits and drawbacks to the use of technology in telegenetics and overall found the use of telegenetics and at-home genetic testing to be convenient. Both groups also noted having to make changes in their daily lives and future planning as a consequence of the positive genetic testing results. However, access to follow-up care differed between local and non-local participants, with more local participants having scheduled and attended appointments with the appropriate medical providers compared to non-local participants. Supplying non-local patients access to remote cardiogenetic testing may therefore require careful consideration in how to ensure proper follow-up care for genotype positive patients and may necessitate the involvement of national professional or patient-centered organizations to help streamline the referral process. [ABSTRACT FROM AUTHOR]

The increased utilization of clinical genomic sequencing in the past decade has ushered in the era of genomic medicine, requiring genetics providers to acquire new skills and adapt their practices. The change in workplace responsibilities of clinical/medical geneticists (CMGs) and genetic counselors (GCs) in North America, due to the evolution of genetic testing, has not been studied. We surveyed CMGs (n = 80) and GCs (n = 127) with experience in general/pediatric genetics to describe their current practice of clinical tasks and the change in regularity of performing these tasks over the past 5–10 years. Currently, complementarity of responsibilities between CMGs and GCs clearly exists but providers who have been in the field for longer have noted role changes. Trends indicate that fewer experienced CMGs perform physical exams and select genetic tests than before and fewer experienced GCs complete requisitions and write result letters. The frequency of CMGs and GCs who investigate genetic test results, however, has increased. This study provides insight into the changing landscape of clinical genetics practice. Our findings suggest that the roles and responsibilities of CMGs and GCs have shifted in the past decade. [ABSTRACT FROM AUTHOR]

Purpose: The precision medicine era has seen increased utilization of artificial intelligence (AI) in the field of genetics. We sought to explore the ways that genetic counselors (GCs) currently use the publicly accessible AI tool Chat Generative Pre‐trained Transformer (ChatGPT) in their work. Methods: GCs in North America were surveyed about how ChatGPT is used in different aspects of their work. Descriptive statistics were reported through frequencies and means. Results: Of 118 GCs who completed the survey, 33.8% (40) reported using ChatGPT in their work; 47.5% (19) use it in clinical practice, 35% (14) use it in education, and 32.5% (13) use it in research. Most GCs (62.7%; 74) felt that it saves time on administrative tasks but the majority (82.2%; 97) felt that a paramount challenge was the risk of obtaining incorrect information. The majority of GCs not using ChatGPT (58.9%; 46) felt it was not necessary for their work. Conclusion: A considerable number of GCs in the field are using ChatGPT in different ways, but it is primarily helpful with tasks that involve writing. It has potential to streamline workflow issues encountered in clinical genetics, but practitioners need to be informed and uniformly trained about its limitations. [ABSTRACT FROM AUTHOR]

Objective: Hispanics continue to face challenges when trying to access health care, including epilepsy care and genetic‐related health care services. This study examined epilepsy genetic knowledge and beliefs in this historically underserved population. Methods: Questionnaires were completed by 641 adults with epilepsy without identified cause, of whom 122 self‐identified as Hispanic or Latino and 519 as non‐Hispanic. Participants were asked about their views on the contribution of genetics to the cause of their epilepsy ("genetic attribution"), optimism for advancements in epilepsy genetic research ("genetic optimism"), basic genetic knowledge, and epilepsy‐specific genetic knowledge. Generalized linear models were used to compare the two groups in the means of quantitative measures and percents answered correctly for individual genetic knowledge items. Analyses were adjusted for age, sex, education, religion, family history of epilepsy, and time since last seizure. Results: Hispanics did not differ from non‐Hispanics in genetic attribution, genetic optimism, or number of six basic genetic knowledge items answered correctly. The number of nine epilepsy‐specific genetic knowledge items answered correctly was significantly lower for Hispanics than non‐Hispanics (adjusted mean = 6.0 vs. 6.7, p <.001). After adjustment for education and other potential mediators, the proportion answered correctly was significantly lower for Hispanics than non‐Hispanics for only two items related to family history and penetrance of epilepsy‐related genes. Only 54% of Hispanics and 61% of non‐Hispanics answered correctly that "If a person has epilepsy, his or her relatives have an increased chance of getting epilepsy." Significance: Despite large differences in sociodemographic variables including education, most attitudes and beliefs about genetics were similar in Hispanics and non‐Hispanics. Epilepsy‐specific genetic knowledge was lower among Hispanics than non‐Hispanics, and this difference was mostly mediated by differences in demographic variables. Genetic counseling should address key concepts related to epilepsy genetics to ensure they are well understood by both Hispanic and non‐Hispanic patients. [ABSTRACT FROM AUTHOR]

Professional interpreters are an integral component of healthcare for Spanish‐speaking individuals with limited English proficiency (LEP). Research has demonstrated that errors in interpretation are common and can contribute to poor outcomes for Spanish‐speaking clients. Providers with some Spanish proficiency may be able to detect clinically significant interpretation errors, potentially limiting negative clinical outcomes and helping to reduce health disparities for clients with LEP. This study aimed to identify the level of Spanish proficiency necessary for genetic counselors to be able to detect a majority of clinically significant errors made by a professional interpreter during a reproductive genetic counseling session. Practicing genetic counselors and genetic counseling graduate students were surveyed regarding their Spanish language background, experience working with interpreters, and self‐rated Spanish proficiency. Participants then watched short video clips from three simulated reproductive genetic counseling sessions conducted with a professional interpreter and were tasked with identifying clinically significant interpretation errors. Survey responses were analyzed from 118 participants who met eligibility criteria. Participants who reported "basic" and "fair" Spanish proficiency detected an average of 36.5% and 67% of clinically significant errors, respectively. Those reporting "good" proficiency or higher detected more than 80% of errors. Overall self‐rated Spanish proficiency was positively correlated with years of Spanish language education and individual measures of speaking, listening, and reading proficiency, indicating that self‐report may be a reasonable measure of proficiency when the goal is error detection in an interpreted session. Genetic counselors with even minimal Spanish proficiency can detect clinically significant interpretation errors, allowing for the correction of these errors during the session. Genetic counselors with "basic" and "fair" may consider genetic counseling‐specific Spanish language classes to increase their proficiency to be able to detect a majority of interpretation errors and thereby improve the quality of care and reduce health disparities for Spanish‐speaking clients. [ABSTRACT FROM AUTHOR]

Objective: Exome sequencing (ES) has played an important role in the identification of causative variants for individuals with epilepsy and has proven to be a valuable diagnostic tool. Less is known about its clinical utility once a diagnosis is received. This study systematically reviewed the impact of ES results on clinical decision‐making and patient care in a pediatric epilepsy cohort at a tertiary care medical center. Methods: Pediatric patients with unexplained epilepsy were referred by their neurologist, and informed consent was obtained through an institutional review board–approved research ES protocol. For patients who received a genetic diagnosis, a retrospective chart review was completed of the probands and their relatives' medical records prior to and after genetic diagnosis. The following outcomes were explored: provider management recommendations, changes in care actually implemented, and anticipatory guidance provided regarding the proband's condition. Results: Fifty‐three probands met the inclusion criteria. Genetic diagnosis led to at least one provider recommendation in 41.5% families (22/53). Recommendations were observed in the following categories: medication, screening for non‐neurological comorbidities/referrals to specialists, referrals to clinical research/trials, and cascade testing. Anticipatory guidance including information about molecular diagnosis, prognosis, and relevant foundations/advocacy groups was also observed. Significance: Results demonstrate the clinical utility of ES for individuals with epilepsy across multiple aspects of patient care, including anti‐seizure medication (ASM) selection; screening for non‐neurological comorbidities and referrals to appropriate medical specialists; referral to reproductive genetic counseling; and access to research, information, and support resources. To our knowledge, this is the first study to evaluate the clinical utility of ES for a pediatric epilepsy cohort with broad epilepsy phenotypes. This work supports the implementation of ES as part of clinical care in this population. [ABSTRACT FROM AUTHOR]

Graduation from a genetic counseling graduate program accredited by the Accreditation Council of Genetic Counseling and certification obtained by passing the American Board of Genetic Counseling (ABGC) certification examination are increasingly required to practice as a genetic counselor in the USA. Despite the ABGC certification examination serving as a gateway to the genetic counseling career, there have been no research studies to date that have examined what variables are associated with examination performance. Therefore, the Association of Genetic Counseling Program Directors established a Task Force to assess whether trainee demographics, Grade point average (GPA) and Graduate Record Exam (GRE®) percentile scores are associated with passing the ABGC certification examination on the first attempt. We surveyed accredited genetic counseling graduate programs in North America and gathered demographic data, admissions variables, and certification examination outcome data for 1,494 trainees from 24 training programs, representing approximately 60.5% of matriculants between 2007 and 2016. Univariable analysis was performed to assess associations between admissions variables and categorical outcome (pass vs. fail) on the certification examination using Wilcoxon rank‐sum or Fisher's exact test. Variables significantly associated with the categorical board outcome were then entered in a stepwise model selection procedure. In stepwise logistic regression, trainees with higher GPA (OR = 3.41; 95% CI = 1.99, 5.83), higher verbal (OR = 1.02; 95% CI = 1.01, 1.03) and quantitative (OR = 1.02; 95% CI = 1.01, 1.03) GRE® scores, female trainees (OR = 2.95; 95% CI = 1.70, 5.12), and White trainees (OR 3.37; 95% CI = 2.14, 5.30) had higher odds of passing the certification examination on the first attempt. As programs move to a holistic approach to graduate admissions in order to improve access to the genetic counseling profession, our results may influence programs to provide additional preparation for the certification examination for all trainees. In addition, genetic counseling professional organizations should continue to work together to assess and eliminate outcome disparities in admissions, training, and certification processes. [ABSTRACT FROM AUTHOR]

Objective: Numerous genetic testing options for individuals with epilepsy have emerged over the past decade without clear guidelines regarding optimal testing strategies. We performed a systematic evidence review (SER) and conducted meta‐analyses of the diagnostic yield of genetic tests commonly utilized for patients with epilepsy. We also assessed nonyield outcomes (NYOs) such as changes in treatment and/or management, prognostic information, recurrence risk determination, and genetic counseling. Methods: We performed an SER, in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses), using PubMed, Embase, CINAHL, and Cochrane Central through December of 2020. We included studies that utilized genome sequencing (GS), exome sequencing (ES), multigene panel (MGP), and/or genome‐wide comparative genomic hybridization/chromosomal microarray (CGH/CMA) in cohorts (n ≥ 10) ascertained for epilepsy. Quality assessment was undertaken using ROBINS‐I (Risk of Bias in Non‐Randomized Studies of Interventions). We estimated diagnostic yields and 95% confidence intervals with random effects meta‐analyses and narratively synthesized NYOs. Results: From 5985 nonduplicated articles published through 2020, 154 met inclusion criteria and were included in meta‐analyses of diagnostic yield; 43 of those were included in the NYO synthesis. The overall diagnostic yield across all test modalities was 17%, with the highest yield for GS (48%), followed by ES (24%), MGP (19%), and CGH/CMA (9%). The only phenotypic factors that were significantly associated with increased yield were (1) the presence of developmental and epileptic encephalopathy and/or (2) the presence of neurodevelopmental comorbidities. Studies reporting NYOs addressed clinical and personal utility of testing. Significance: This comprehensive SER, focused specifically on the literature regarding patients with epilepsy, provides a comparative assessment of the yield of clinically available tests, which will help shape clinician decision‐making and policy regarding insurance coverage for genetic testing. We highlight the need for prospective assessment of the clinical and personal utility of genetic testing for patients with epilepsy and for standardization in reporting patient characteristics. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has ravaged the globe in the past year, demanding shifts in all aspects of life including health profession education. The New York City area was the first major United States epicenter and is home to four genetic counseling graduate programs. We set out to explore the multifaceted programmatic changes required from the four institutions in an early pandemic epicenter, providing the longest time horizon available for assessing the implications of this restructuring on graduate education in the profession. Using practitioner‐based enquiry, our iterative reflections identified three phases of COVID‐19 response within our programs from March through December 2020. The spring months were marked by significant upheaval and reactivity, with a focus on stabilizing our programs in an unstable environment that included a significant medical response required in our area. By summer, we were reinvesting time and energy into our programs and prioritizing best practices in online learning. Relative predictability returned in the fall with noticeable improvements in flexibility and proactive problem‐solving within our new environment. We have begun to identify changes in both curricula and operations that are likely to become more permanent. Telehealth fieldwork, remote supervision, simulated cases with standardized clients, and virtual recruitment and admission events are some key examples. We explored early outcome measures, such as enrollment, retention, course evaluations, and student academic and fieldwork progress, all indicating little change from prior to the pandemic to date. Overall, we found our programs, and genetic counseling graduate education more broadly, to be much more resilient and flexible than we would ever have realized. The COVID‐19 pandemic has awakened in us a desire to move ahead with reduced barriers to educational innovation. [ABSTRACT FROM AUTHOR]

The goal of this practice resource is to provide genetic counselors and other healthcare professionals with a resource to reference when providing genetic counseling services to individuals and families undergoing evaluation for neurofibromatosis (NF) or who have received a diagnosis of NF, including NF1, NF2, and schwannomatosis. This resource represents the opinions of a multi‐center working group of Certified Genetic Counselors with experience in the care of individuals with NF, providing topics to be considered for the incorporation into a clinical genetic counseling session. [ABSTRACT FROM AUTHOR]

Through self‐reflection, self‐education, and with a learning mindset each of us has embarked on a personal path to understand the impact of racism in our personal and professional lives. This personal work is ongoing, though it was through our individual paths that led us to engage in dialogue on race and racism at the 38th National Society of Genetic Counselors Annual Conference. We initially did not know each other; however, we were drawn by a mutual desire to further the conversation and sought connection with each other after the Conversations Around Diversity Platform Presentations. Through sustained, open dialogue we created a brave space for sharing our emotional and intellectual responses to the conference. Through this dialogue and through written reflections, we recognized an emboldened urgency to author a joint reflection on our shared responsibility as genetic counseling training program leaders to use our privilege in service to our students and future students. We have the evidence that we are not a diverse profession. We have more evidence now than we did before that our profession performs poorly with regards to inclusivity. Our inability to acknowledge, address, and discuss racism and other forms of oppression is damaging to each of us individually and as a group of professionals. We owe it to ourselves, our students, our patients, and colleagues to name our learned biases and behaviors, own them and interrupt them. [ABSTRACT FROM AUTHOR]

Genetic counselors working in a clinical setting may find themselves recruiting, enrolling, and returning results for genomic research, and existing clinical relationships with study participants may impact these research interactions. We present a qualitative study using semi-structured interviews of participants enrolled in a genome sequencing/exome sequencing (GS/ES) study at the same institution where they receive clinical care. Interviews were coded for motivations to participate and expectations of this research. The interviews revealed common motivations for participation, including altruism and hope for benefit for themselves, family members, and/or others with their condition. Additionally, themes emerged related to unintentional influence based on trust of the clinical provider that recruited them to the study. Participant trust in the enrolling provider at times appeared to extend to the study team to decide which research results to return and to do so in an appropriate format. Participants also based expectations for research results return on previous clinical genetic testing experiences, which may or may not be realistic depending on study design. It is imperative that genetic counselors enrolling patients into research studies be aware of the potential influence of their clinical relationship on potential subjects, be transparent about their role on the study team, and help set expectations about the study process, including results return. [ABSTRACT FROM AUTHOR]

Supervision is a practice that is utilized by a variety of practitioners to hone their counseling skills. Genetic counselors have embraced the supervision process, and some seek out supervision in a group setting with peers. Researchers have described the structure and content of genetic counseling peer supervision groups, and provided evidence for the benefits of seeking peer supervision. This study aimed to describe the interpersonal aspects of one genetic counseling peer supervision group, including personality traits and group dynamics, and how those factors influenced our experiences within the group. We also describe how the process of evaluating these factors impacted us individually and collectively. There was consensus that the group was a safe and trusting one, which was united by similar goals and mutual respect. Members reported gaining insights about how their own personality functioned within the group milieu, and also how the group setting impacted them. Based on our experiences, we recommend that other peer supervision groups consider similar self-evaluations on a periodic basis, both to enhance group functioning and to allow for increased self-awareness and professional growth. [ABSTRACT FROM AUTHOR]

The first practice based competencies (PBCs) for the field of genetic counseling were adopted by the American Board of Genetic Counseling (ABGC), 1996. Since that time, there has been significant growth in established and new work settings (clinical and non-clinical) and changes in service delivery models and the roles of genetic counselors. These changes prompted the ABGC to appoint a PBC Task Force in 2011 to review the PBCs with respect to their current relevance and to revise and update them as necessary. There are four domains in the revised PBCs: (I) Genetics Expertise and Analysis (II) Interpersonal, Psychosocial and Counseling Skills (III) Education and (IV) Professional Development and Practice. There are 22 competencies, each clarified with learning objectives or samples of activities and skills; a glossary is included. New competencies were added that address genomics, genetic testing and genetic counselors' roles in risk assessment, education, supervision, conducting research and presenting research options to patients. With PBCs serving as the pre-defined abilities or outcomes of training, graduating genetic counselors will be well prepared to enter the field with a minimum level of skills and abilities. A description of the Task Force's work, key changes and the 2013 PBCs are presented herein. [ABSTRACT FROM AUTHOR]

Despite the high prevalence and significant morbidity of spinal anomalies in neurofibromatosis type 1 (NF1), the pathogenesis of these defects remains largely unknown. Here, we present two murine models: Nf1flox/−;PeriCre and Nf1flox/−;Col.2.3Cre mice, which recapitulate spinal deformities seen in the human disease. Dynamic histomorphometry and microtomographic studies show recalcitrant bone remodeling and distorted bone microarchitecture within the vertebral spine of Nf1flox/−;PeriCre and Nf1flox/−;Col2.3Cre mice, with analogous histological features present in a human patient with dystrophic scoliosis. Intriguingly, 36–60% of Nf1flox/−;PeriCre and Nf1flox/−;Col2.3Cre mice exhibit segmental vertebral fusion anomalies with boney obliteration of the intervertebral disc (IVD). While analogous findings have not yet been reported in the NF1 patient population, we herein present two case reports of IVD defects and interarticular vertebral fusion in patients with NF1. Collectively, these data provide novel insights regarding the pathophysiology of dystrophic spinal anomalies in NF1, and provide impetus for future radiographic analyses of larger patient cohorts to determine whether IVD and vertebral fusion defects may have been previously overlooked or underreported in the NF1 patient population. [ABSTRACT FROM AUTHOR]

Genomic sequencing technology is increasingly used in genetic research. Studies of informed consent for exome and genome sequencing (ES/GS) research have largely involved hypothetical scenarios or healthy individuals enrolling in population-based studies. Studies have yet to explore the consent experiences of adults with inherited disease. We conducted a qualitative interview study of 15 adults recently enrolled in a large-scale ES/GS study (11 affected adults, four parents of affected children). Our study had two goals: (1) to explore three theoretical barriers to consent for ES/GS research (interpretive/technical complexity, possibility of incidental findings, and risks of loss of privacy); and (2) to explore how interviewees experienced the consent process. Interviewees could articulate study goals and processes, describe incidental findings, discuss risks of privacy loss, and reflect on their consent experience. Few expected the study would identify the genetic cause of their condition. All elected to receive incidental findings. Interviewees acknowledged paying little attention to potential implications of incidental findings in light of more pressing goals of supporting research regarding their own medical conditions. Interviewees suggested that experience living with a genetic condition prepared them to adjust to incidental findings. Interviewees also expressed little concern about loss of confidentiality of study data. Some experienced the consent process as very long. None desired reconsent prior to return of study results. Families with inherited disease likely would benefit from a consent process in which study risks and benefits were discussed in the context of prior experiences with genetic research and genetic disease. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Constitutional SMARCB1 mutations at 22q11.23 have been found in ∼50% of familial and <10% of sporadic schwannomatosis cases. We sequenced highly conserved regions along 22q from eight individuals with schwannomatosis whose schwannomas involved somatic loss of one copy of 22q, encompassing SMARCB1 and NF2, with a different somatic mutation of the other NF2 allele in every schwannoma but no mutation of the remaining SMARCB1 allele in blood and tumor samples. LZTR1 germline mutations were identified in seven of the eight cases. LZTR1 sequencing in 12 further cases with the same molecular signature identified 9 additional germline mutations. Loss of heterozygosity with retention of an LZTR1 mutation was present in all 25 schwannomas studied. Mutations segregated with disease in all available affected first-degree relatives, although four asymptomatic parents also carried an LZTR1 mutation. Our findings identify LZTR1 as a gene predisposing to an autosomal dominant inherited disorder of multiple schwannomas in ∼80% of 22q-related schwannomatosis cases lacking mutation in SMARCB1. [ABSTRACT FROM AUTHOR]

To describe the spectrum and associated clinical features of peripheral and cerebral vasculopathy in pediatric patients with neurofibromatosis type 1, children seen at a single center from 2000 to 2010 with appropriate imaging studies were identified. Scans were assessed for vascular disease by 2 pediatric neuroradiologists. Of 181 children, 80 had pertinent imaging studies: 77 had brain imaging, 6 had peripheral imaging, and 3 had both. Vasculopathy was identified in 14/80 children (18%, minimum prevalence of 14/181; 8%). Of those with vascular abnormalities, 2/14 had peripheral vasculopathy (1% minimum prevalence) and 12/14 had cerebrovascular abnormalities (7% minimum prevalence). No associations were found between vasculopathy and common clinical features of neurofibromatosis type 1, including optic pathway glioma, plexiform neurofibroma, skeletal abnormalities, attention-deficit hyperactivity disorder (ADHD), or suspected learning disability. Both peripheral and cerebral vasculopathy are important complications of pediatric neurofibromatosis type 1 and should be considered in the management of this complex disease. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder associated with increased risk for neoplasms. Two studies in the United Kingdom have indicated that women with NF1 (particularly women under 50) may also be at increased risk of breast cancer. No such study has been done to date in the United States. Chart review for breast cancer diagnoses was undertaken for 126 women with NF1 followed at Johns Hopkins who were 20 years of age or older. Four of 126 women who met eligibility criteria were diagnosed with breast cancer (3.2% over 15 years). The unadjusted standardized incidence ratio (SIR) for breast cancer in the NF1 population between the ages of 20 and 49 was 2.68 ( P = 0.076, 95% CI 0.68-7.29) based on incidence rates of breast cancer in the general population taken from the Surveillance Epidemiology and End Results (SEER) database. The unadjusted SIR for women with NF1 ≥50 was 0.81 ( P = 0.84, 95% CI 0.041-4.01). When adjusted for race, the rate of NF1 in the general population and time of diagnosis, the SIR was 4.41 ( P = 0.0049, 95% CI 1.12-12.00) for women <50 versus 0.94 ( P = 0.95, 95% CI 0.047-4.65) for women ≥50. The trend of a higher-than-expected number of breast cancer cases in women <50 with NF1 agrees with the prior studies from the literature. Cumulatively, the data suggests an increased risk of breast cancer for women with NF1 < 50 years old, implying a need for closer surveillance and the establishment of screening guidelines for this patient population. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Metanephric stromal tumor (MST) is a recently recognized benign renal stromal tumor. MST is thought to be part of a spectrum of benign metanephric renal lesions, which also includes the epithelial lesion metanephric adenoma and the mixed stromal–epithelial lesion metanephric adenofibroma. Metanephric lesions may represent hyperdifferentiated counterparts to Wilms’ tumor (WT). MST characteristically shows renovascular angiodysplasia and juxtaglomerular (JG) cell hyperplasia. This is remarkably similar to the renal pathology described in neurofibromatosis-1 (NF-1) syndrome, a condition which is also associated with WT. Here, we report the first case of MST arising in a patient with NF-1. The patient presented with hypertension, and the MST was associated with florid angiodysplasia and JG cell hyperplasia. This case tightens the link between NF-1, WT, and MST. [ABSTRACT FROM PUBLISHER]