Genetic counselling and testing for inherited dementia: single-centre evaluation of the consensus Italian DIAfN protocol

Abstract Background A consensus protocol for genetic counselling and testing of familial dementia, the Italian Dominantly Inherited Alzheimer’s and Frontotemporal Network (IT-DIAfN) protocol, has been developed in Italy by a network of expert dementia centres. The aim of this study is to evaluate feasibility and acceptability of the genetic counselling and testing process, as undertaken according to the IT-DIAfN protocol in one of the IT-DIAfN dementia research centres. Methods The protocol was tested by a multidisciplinary team at the IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy, on affected individuals with suspected inherited forms of Alzheimer’s disease (AD) or frontotemporal dementia (FTD), and to healthy at-risk relatives. The genetic counselling and testing process consisted of (i) pre-test consultation and psychological assessment (ii) genetic testing, (iii) genetic test result disclosure and (iv) follow-up consultation and psychological assessment. Results Twenty affected individuals from 17 families fulfilled the family history criteria of the IT-DIAfN protocol for suspected inherited dementia (17 for AD, 2 for FTD, 1 for inclusion body myopathy with Paget disease of bone and frontotemporal dementia) and were included in the protocol. Nineteen out of 20 affected individuals received the genetic test result (one left after the pre-test consultation being not ready to cope with an unfavourable outcome). A pathogenic mutation was found in 6 affected individuals (1 in PSEN1, 2 in PSEN2, 1 in GRN, 1 in MAPT, 1 in VCP). Eleven healthy at-risk relatives asked to undergo predictive testing and were included in the protocol. Three completed the protocol, including follow-up; one did not ask for the genetic test result after genetic testing; and eight withdrew before the genetic testing, mainly due to an increased awareness about the possible consequences of an unfavourable test result. To date, no catastrophic reactions were reported at the follow-up. Conclusions Our case series shows that a structured genetic counselling and testing protocol for inherited dementia can be implemented in both affected individuals and at-risk relatives in a research setting. The procedure was shown to be safe in terms of occurrence of catastrophic events. A formal validation in larger cohorts is needed.

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Melanoma genetic testing to promote reductions in tanning: Results from the Utah BRIGHT project.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.1582 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 1582-1582

Author(s):

Lisa Aspinwall ◽

Tammy K. Stump ◽

Jennifer M. Taber ◽

Wendy Kohlmann ◽

Marjan Champine ◽

...

Keyword(s):

Genetic Testing ◽

Family History ◽

Genetic Test ◽

Disease Onset ◽

Skin Type ◽

Control Group ◽

Genetic Test Result ◽

Family Medical History ◽

Management Recommendations ◽

Test Result

1582 Background: Predictive genetic testing for familial cancer may alert people to highly elevated risk prior to disease onset. Genetic test reporting has been shown to improve uptake of prophylactic screening and procedures, but whether test reporting also promotes increased performance of primary preventive behavior is unknown. Methods: Unaffected adult participants ( N= 124) from high-risk melanoma families, ages 16-69 (mean = 35.24, 52% men) were enrolled. Participants from families that carried a CDKN2A/p16 mutation received a personal genetic test result and counseling about management recommendations whereas control participants from families without a CDKN2A/16 mutation received equivalent counseling and management recommendations based on family history alone. Photoprotection outcomes were compared between CDKN2A/p16 participants (31 carriers, 44 noncarriers) and the no-test control group ( n= 49), allowing the effects of receiving a genetic test result to be distinguished from the effects of counseling alone. Assessments were seasonally timed to capture tanning during the summer months. Melanin Index (MI) scores, measures of skin tanning obtained through reflectance spectroscopy, were assessed at the dorsal wrist and face. Tanning of the dorsal wrist and face were calculated by subtracting baseline MI scores at an unexposed site on the same individual. Results: Multilevel model analyses examined changes in tanning over time while controlling for clinician-rated skin type, age, gender, date of assessment, and group differences in phenotypic factors and family medical history. Participants who received positive test results were significantly less tan at the wrist one year after their previous summer baseline ( b= -.11, p< .001). No-test controls and noncarriers had no change in tanning. The magnitude of decrease in tanning measurements observed among CDKN2A/ p16 carriers approximated one skin type. Facial tanning did not differ from baseline for any group. Conclusions: A positive melanoma genetic test result promotes reduced UVR exposure. Future research should examine why positive genetic test reports were more motivating to patients than equivalent counseling based on family history.

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Colorectal Cancer Risk Perception on the Basis of Genetic Test Results in Individuals at Risk for Lynch Syndrome

Journal of Clinical Oncology ◽

10.1200/jco.2008.18.6940 ◽

2009 ◽

Vol 27 (24) ◽

pp. 3981-3986 ◽

Cited By ~ 16

Author(s):

Shilpa Grover ◽

Elena M. Stoffel ◽

Rowena C. Mercado ◽

Beth M. Ford ◽

Wendy K. Kohlman ◽

...

Keyword(s):

Colorectal Cancer ◽

Genetic Testing ◽

Risk Perception ◽

Cancer Risk ◽

Lynch Syndrome ◽

Genetic Test ◽

Genetic Test Result ◽

Test Results ◽

Genetic Test Results ◽

Test Result

Purpose Lynch syndrome is associated with inherited germline mutations in mismatch repair (MMR) genes. Genetic testing in high-risk individuals may yield indeterminate results if no mutation is found or if a mutation of unclear pathogenic significance is observed. There are limited data regarding how well patients with Lynch syndrome understand the clinical implications of genetic test results. This study examines colorectal cancer (CRC) risk perception in individuals tested for MMR mutations and identifies the factors associated with an appropriate interpretation of their cancer risk. Patients and Methods A total of 159 individuals who met the Revised Bethesda Guidelines and had previously undergone genetic testing completed a questionnaire eliciting demographic data, cancer history, genetic test results, and an estimate of their CRC risk. Associations between clinical factors, genetic test results, and CRC risk perception were explored using multivariable analyses. Results Of the 100 individuals with a pathogenic mutation (true positive), 90 (90%) correctly estimated their CRC risk as “high” or “very high” compared with other individuals their age. However, only 23 (62%) of 37 individuals with an indeterminate genetic test result correctly estimated their risk. Individuals with a history of Lynch syndrome–associated cancer (odds ratio [OR], 0.1; 95% CI, 0.1 to 0.6) or indeterminate genetic test results (OR, 0.2; 95% CI, 0.1 to 0.6) were significantly less likely to estimate their CRC risk as increased. Conclusion Patients at risk for Lynch syndrome with an indeterminate genetic test result may be falsely reassured. It is important that health care providers continue to discuss the implications of uninformative results on lifetime cancer risk.

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Patient recommendations for content and design for electronic return of genetic test results: An interview study among patients who accessed their genetic test results online (Preprint)

10.2196/preprints.29706 ◽

2021 ◽

Author(s):

Diane M Korngiebel ◽

Kathleen McGlone West

Keyword(s):

Patient Preferences ◽

Genetic Test ◽

Smartphone Application ◽

Patient Portal ◽

Genetic Test Result ◽

Test Results ◽

User Centered Design ◽

Detailed Report ◽

Genetic Test Results ◽

Test Result

BACKGROUND Genetic test results will be increasingly made available electronically as more patient-facing tools are developed; however, little research has been done that collects patient preferences for content and design before creating results templates. OBJECTIVE This study identifies patient preferences for electronic return of genetic test results, including what considerations should be prioritized for content and design. METHODS Following User-Centered Design methods, 59 interviews were conducted using semi-structured protocols. The interviews explored content and design issues for patient portal results return for patients who received electronic results for specific types of genetic tests (pharmacogenomic, hereditary blood disorders, and positive and negative risk results for heritable cancers) or who had electronically received any type of genetic test result as well as a non-genetic test result. RESULTS In general, a majority of participants felt that there always needed to be some clinician involvement in electronic results return and that electronic coversheets with simple summaries would be helpful for facilitating that. Coversheet summaries could accompany, but not replace, the more detailed report. Participants had specific suggestions for those results summaries, such as only reporting the information that was most important for patients to understand, including next steps, and to do so using clear language free of medical jargon. Electronic results return should also include explicit encouragement for patients to contact providers with questions. Finally, many participants preferred to manage their care using their smartphones, particularly in instances where they needed to access health information on the go. CONCLUSIONS Participants recommended that a patient-friendly front section accompany the more detailed report and made suggestions for organization, content, and wording. Many used their smartphones regularly to access test results, therefore, health systems and patient portal software vendors should accommodate smartphone application design and web portal design concomitantly when developing results return platforms. CLINICALTRIAL N/A

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Using a genetic test result in the care of family members: how does the duty of confidentiality apply?

European Journal of Human Genetics ◽

10.1038/s41431-018-0138-y ◽

2018 ◽

Vol 26 (7) ◽

pp. 955-959 ◽

Cited By ~ 10

Author(s):

Michael Parker ◽

Anneke Lucassen

Keyword(s):

Genetic Test ◽

Family Members ◽

Genetic Test Result ◽

Test Result

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Education modulates brain maintenance in presymptomatic frontotemporal dementia

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-320439 ◽

2019 ◽

Vol 90 (10) ◽

pp. 1124-1130 ◽

Cited By ~ 7

Author(s):

Stefano Gazzina ◽

Mario Grassi ◽

Enrico Premi ◽

Maura Cosseddu ◽

Antonella Alberici ◽

...

Keyword(s):

At Risk ◽

Frontotemporal Dementia ◽

Grey Matter ◽

Principal Component ◽

Grey Matter Volume ◽

Brain Reserve ◽

Matter Volume ◽

Brain Maintenance ◽

Over Time

ObjectiveCognitively engaging lifestyles have been associated with reduced risk of conversion to dementia. Multiple mechanisms have been advocated, including increased brain volumes (ie, brain reserve) and reduced disease progression (ie, brain maintenance). In cross-sectional studies of presymptomatic frontotemporal dementia (FTD), higher education has been related to increased grey matter volume. Here, we examine the effect of education on grey matter loss over time.MethodsTwo-hundred twenty-nine subjects at-risk of carrying a pathogenic mutation leading to FTD underwent longitudinal cognitive assessment and T1-weighted MRI at baseline and at 1 year follow-up. The first principal component score of the graph-Laplacian Principal Component Analysis on 112 grey matter region-of-interest volumes was used to summarise the grey matter volume (GMV). The effects of education on cognitive performances and GMV at baseline and on the change between 1 year follow-up and baseline (slope) were tested by Structural Equation Modelling.ResultsHighly educated at-risk subjects had better cognition and higher grey matter volume at baseline; moreover, higher educational attainment was associated with slower loss of grey matter over time in mutation carriers.ConclusionsThis longitudinal study demonstrates that even in presence of ongoing pathological processes, education may facilitate both brain reserve and brain maintenance in the presymptomatic phase of genetic FTD.

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Randomized comparison of phone versus in-person BRCA1/2 predisposition genetic test result disclosure counseling

Genetics in Medicine ◽

10.1097/gim.0b013e31812e6220 ◽

2007 ◽

Vol 9 (8) ◽

pp. 487-495 ◽

Cited By ~ 46

Author(s):

Jean Jenkins ◽

Kathleen A Calzone ◽

Eileen Dimond ◽

David J Liewehr ◽

Seth M Steinberg ◽

...

Keyword(s):

Genetic Test ◽

Genetic Test Result ◽

Test Result

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Genetic counselling and personalised risk assessment in the Australian pancreatic cancer screening program

Hereditary Cancer in Clinical Practice ◽

10.1186/s13053-019-0129-1 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 2

Author(s):

Tanya Dwarte ◽

Skye McKay ◽

Amber Johns ◽

Katherine Tucker ◽

Allan D. Spigelman ◽

...

Keyword(s):

Risk Assessment ◽

Pancreatic Cancer ◽

Genetic Testing ◽

High Risk ◽

Genetic Counselling ◽

Screening Program ◽

Pathogenic Variant ◽

Recruitment Strategy ◽

Close Relative

Abstract Background Pancreatic cancer (PC) is an aggressive disease with a dismal 5-year survival rate. Surveillance of high-risk individuals is hoped to improve survival outcomes by detection of precursor lesions or early-stage malignancy. Methods Since 2011, a national high-risk cohort recruited through St Vincent’s Hospital, Sydney, has undergone prospective PC screening incorporating annual endoscopic ultrasound, formal genetic counselling and mutation analysis as appropriate. PancPRO, a Bayesian PC risk assessment model, was used to estimate 5-year and lifetime PC risks for familial pancreatic cancer (FPC) participants and this was compared to their perceived chance of pancreatic and other cancers. Genetic counselling guidelines were developed to improve consistency. Follow-up questionnaires were used to assess the role of genetic counselling and testing. Results We describe the Australian PC screening program design and recruitment strategy and the results of the first 102 individuals who have completed at least one-year of follow-up. Seventy-nine participants met the FPC criteria (≥ two first-degree relatives affected), 22 individuals had both a BRCA2 pathogenic variant and a close relative with PC and one had a clinical diagnosis of Peutz-Jeghers syndrome. Participants reported a high perceived chance of developing PC regardless of their genetic testing status. PancPRO reported FPC participants’ mean 5-year and lifetime PC risks as 1.81% (range 0.2–3.2%) and 10.17% (range 2.4–14.4%), respectively. Participants’ perceived PC chance did not correlate with their PancPRO 5-year (r = − 0.17, p = 0.128) and lifetime PC risks (r = 0.19, p = 0.091). Two-thirds felt that current genetic testing would help them, and 91% of tested participants were glad to have undergone genetic testing. Overall, 79% of participants found genetic counselling to be helpful, and 88% reported they would recommend counselling to their relatives. Conclusions Participants reported multiple benefits of genetic counselling and testing but continue to seek greater clarification about their individual PC risk. Extension of PancPRO is required to enable personalised PC risk assessment for all high-risk sub-groups. More detailed discussion of PC risk for BRCA2 pathogenic variant carriers, providing a written summary in all cases and a plan for genetics review were identified as areas for improvement.

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