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Genetic Testing Preferences of Individuals in Families with Essential Tremor.

ABSTRACT: Background:The search for essential tremor (ET) genes is active, and it is only a matter of time before genetic tests become available. Genetic testing preferences in families have been studied in numerous other neurological disorders but there are no published data about ET. Methods:We surveyed 34 ET probands and their relatives (43 affected, 28 unaffected) enrolled in our Family Study of Essential Tremor to assess their interest in genetic testing. We examined whether clinical factors influenced their interest in testing. Clinical utility ("Your physician will be able to use the information obtained to improve your care") and penetrance ("How likely an individual who carries an ET gene is to develop ET") were defined for participants. Results:Interest in genetic testing was high in ET families (90/105 [85.7%]). There was a significant difference between affected (including probands and affected relatives) and unaffected relatives in terms of their interest in genetic testing, with the former being more interested (70/77 [90.9%] vs. 20/28 [71.4%] p = 0.04). Participants were more likely to want testing in the scenarios with high clinical utility; disease penetrance was not a determining factor (all p < 0.05). Sixteen hypothetical factors were identified that might influence a participant's decision to undergo genetic testing for ET. Discussion:Interest in genetic testing was high in ET families. While genetic testing is not currently available for ET, the hunt for ET genes is ongoing, and this is a highly familial disorder. Understanding genetic testing preferences will greatly aid clinicians once a genetic test becomes available.

SUBMITTER: Naranjo KV

PROVIDER: S-EPMC5876471 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Genetic Testing Preferences of Individuals in Families with Essential Tremor.

Naranjo Kelly V KV Park Jemin J Chen Karen P KP Hernandez Nora N Clark Lorraine N LN Ottman Ruth R Louis Elan D ED

Tremor and other hyperkinetic movements (New York, N.Y.) 20180327

<h4>Background</h4>The search for essential tremor (ET) genes is active, and it is only a matter of time before genetic tests become available. Genetic testing preferences in families have been studied in numerous other neurological disorders but there are no published data about ET.<h4>Methods</h4>We surveyed 34 ET probands and their relatives (43 affected, 28 unaffected) enrolled in our Family Study of Essential Tremor to assess their interest in genetic testing. We examined whether clinical f ...[more]

PMID: 29607242

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Project description:Essential tremor (ET) is among the most common neurological diseases and it often runs in families. How knowledgeable ET patients and their families are about their disease has been the subject of surprisingly little scholarship.To fill this gap in knowledge, we administered a comprehensive 32-item survey (i.e., questions about etiology, pathophysiology, symptoms and signs, natural history, and treatments) to 427 participants, including 76 ET probands, 74 affected relatives (AFRs), 238 unaffected relatives, and 39 spouses of unaffected relatives, all of whom were participating in two ET family studies. We hypothesized that there would be gaps in knowledge about ET and furthermore, that probands and AFRs would be the most knowledgeable, followed by unaffected relatives and then spouses of unaffected relatives, who would be the least knowledgeable.Overall, ET patients lacked knowledge about their disease. Nearly one-third of probands answered "yes" or "do not know" to the question, "is ET the same or different from the type of tremor that many normal people can get when they become old and frail?" A similar proportion did not know whether children could get ET or they responded "no." Nearly one-fourth of affecteds (i.e., probands and AFRs) did not know whether or to what degree (e.g., very well, moderately well, not well) the symptoms of ET could be medically controlled, and 38.0% either reported that there was no brain surgery for ET or reported that they did not know. Nearly 17% of affecteds did not endorse genes as a cause for ET, which was surprising given the fact that this was a family study of ET. Probands and AFRs were the most knowledgeable, followed by unaffected relatives. Spouses of unaffected relatives were the least knowledgeable.We targeted a large group of ET patients and their families, as this group is perhaps most likely to be informed about the disease. ET patients and their AFRs were more knowledgeable about the features of ET than their family members without ET. Overall, however, knowledge of ET was very limited and this lack of knowledge encompassed all aspects of the disease including its underlying causes, the nature of the symptoms and signs, its natural history and its treatment. Further ET awareness education and programs targeting both families of ET patients and the public would help alleviate this gap in knowledge.

Project description:Hereditary nonpolyposis colorectal cancer (HNPCC) is frequently associated with constitutional mutations in a class of genes involved in DNA mismatch repair. We identified 32 kindreds, with germline mutations in one of three genes hMSH2, hMLH1 or hMSH6. In this study, we purposed to evaluate how many high-risk individuals in each family underwent genetic testing: moreover, we assessed how many mutation-positive unaffected individuals accepted colonoscopic surveillance and the main findings of the recommended follow-up. Families were identified through a population-based registry, or referred from other centres. Members of the families were invited for an education session with two members of the staff. When a kindred was consistent with HNPCC, neoplastic tissues were examined for microsatellite instability (MSI) and immunohistochemical expression of MSH2, MLH1 and MSH6 proteins. Moreover, constitutional mutations were searched by SSCP or direct sequencing of the whole genomic region. Of the 164 subjects assessed by genetic testing, 89 were gene carriers (66 affected - that is, with HNPCC-related cancer diagnosis - and 23 unaffected) and 75 tested negative. Among the 23 unaffected gene carriers, 18 (78.3%) underwent colonoscopy and four declined. On a total of 292 first degree at risk of cancer, 194 (66.4%) did not undergo genetic testing. The main reasons for this were: (a) difficulty to reach family members at risk, (b) lack of collaboration, (c) lack of interest in preventive medicine or 'fatalistic' attitude towards cancer occurrence. The number of colorectal lesions detected at endoscopy in gene carriers was significantly (P<0.01) higher than in controls (noncarriers). We conclude that a large fraction of high-risk individuals in mutation-positive HNPCC families does not undergo genetic testing, despite the benefits of molecular screening and endoscopic surveillance. This clearly indicates that there are still barriers to genetic testing in HNPCC, and that we are unable to provide adequate protection against cancer development in these families.

Project description:BACKGROUND:Action tremor is the hallmark feature of essential tremor (ET). While the tremor typically is mildly asymmetric, in some patients, it is markedly asymmetric. There are few data on factors that influence this asymmetry. ET is also a highly familial disease. Whether the tremor asymmetry profile (i.e., differential expression of tremor in each arm in a given patient) is similar across family members is not known. The alternative possibility is that this feature is not heritable. There are no published data addressing this issue. The aim of this study was to determine whether the extent of action tremor asymmetry ran in ET families. METHODS:ET probands and relatives were enrolled in a genetic study at Yale and Columbia Universities. An in-person evaluation included a videotaped neurological examination, including a detailed assessment of tremors. A senior movement disorders neurologist reviewed all videotaped examinations, and the severity of postural and kinetic arm tremors was rated on 12 examination items using a reliable rating scale. The tremor asymmetry index = right arm tremor score - left arm tremor score. We used a bivariate linear regression model to assess the predictors of the tremor asymmetry index in relatives; this model used the tremor asymmetry index in the proband as a primary predictor of interest. In an analysis of variance (ANOVA), we tested for heterogeneity across families in the tremor asymmetry index (i.e., to see whether there was a significant family effect). RESULTS:There were 187 enrollees (59 probands, 128 affected relatives). In a bivariate linear regression model, the tremor asymmetry index in the proband was not a predictor of the tremor asymmetry index in their relatives (p = 0.66). In an ANOVA, family grouping did not explain a significant proportion of the total variance in the tremor asymmetry index (p = 0.56). CONCLUSION:Tremor asymmetry did not aggregate in families with ET. Therefore, this does not seem to be a disease feature that is heritable. These data will provide added value to the clinical dialog, giving patients one more piece of information about the way the disease manifests within families.

Project description:Essential tremor (ET) is one of the most common movement disorders. The etiology of ET remains largely unexplained. Whole genome sequencing (WGS) is likely to be of value in understanding a large proportion of ET with Mendelian and complex disease inheritance patterns. In ET families with Mendelian inheritance patterns, WGS may lead to gene identification where WES analysis failed to identify the causative single nucleotide variant (SNV) or indel due to incomplete coverage of the entire coding region of the genome, in addition to accurate detection of larger structural variants (SVs) and copy number variants (CNVs). Alternatively, in ET families with complex disease inheritance patterns with gene x gene and gene x environment interactions enrichment of functional rare coding and non-coding variants may explain the heritability of ET. We performed WGS in eight ET families (n = 40 individuals) enrolled in the Family Study of Essential Tremor. The analysis included filtering WGS data based on allele frequency in population databases, rare SNV and indel classification and association testing using the Mixed-Model Kernel Based Adaptive Cluster (MM-KBAC) test. A separate analysis of rare SV and CNVs segregating within ET families was also performed. Prioritization of candidate genes identified within families was performed using phenolyzer. WGS analysis identified candidate genes for ET in 5/8 (62.5%) of the families analyzed. WES analysis in a subset of these families in our previously published study failed to identify candidate genes. In one family, we identified a deleterious and damaging variant (c.1367G>A, p.(Arg456Gln)) in the candidate gene, CACNA1G, which encodes the pore forming subunit of T-type Ca(2+) channels, CaV3.1, and is expressed in various motor pathways and has been previously implicated in neuronal autorhythmicity and ET. Other candidate genes identified include SLIT3 which encodes an axon guidance molecule and in three families, phenolyzer prioritized genes that are associated with hereditary neuropathies (family A, KARS, family B, KIF5A and family F, NTRK1). Functional studies of CACNA1G and SLIT3 suggest a role for these genes in ET disease pathogenesis.

Project description:BackgroundThe American College of Obstetricians and Gynecologists recommends prenatal genetic testing (PGT) be offered to all pregnant persons regardless of known risk factors. However, significant racial/ethnic differences exist regarding acceptance of PGT contributing to disparities. Latinas (Latinx), one of the fastest growing ethnic groups in the United States, have low PGT acceptance rates. This systematic scoping review aimed to provide a landscape of existing literature on Latinx individuals' knowledge of, preferences for, and experiences with prenatal and preconception genetic testing. Synthesizing the current state of the science may inform development of culturally tailored interventions to support high-quality PGT decisions (e.g., informed, aligned with a pregnant persons' values).MethodsWe conducted a structured, systematic literature search of published articles and gray literature in electronic databases (PubMed, PsycINFO, CINAHL, Medline, Embase, Eric, Social Services Abstracts, and PsycArticles). Articles in English published prior to March 2021 were retrieved relating to genetics, pregnancy, and Latina women. Articles underwent title, abstract and full-text review by independent investigators to assess inclusion and exclusion criteria. Risk of bias was evaluated by two investigators. Iterative thematic analysis was employed to group study findings into themes to identify possible targets for interventions.ResultsThe search generated 5511 unique articles. After title screening, 335 underwent abstract review and subsequently 61 full-text review. Twenty-eight studies met inclusion criteria and 7 additional studies were included after reviewing reference lists. Three overarching themes emerged: genetic knowledge/literacy (26/35, 74%), provider (mis)communication/patient satisfaction (21/35, 60%), and cross-cultural beliefs (12/35, 34%). Studies indicate discordant patient-provider language (n = 5), miscommunication (n = 4), and lack of concordant decision-making (n = 4) pose barriers to high-quality PGT decisions. Immigration status (n = 1) and religious beliefs (n = 5) are additional factors influencing PGT decisions.ConclusionsIdentified studies suggest that cultural and linguistic factors affect Latinx PGT decision-making. Latinx individual's comprehension and recall of PGT information is enhanced by culturally and linguistically concordant providers-suggesting that culturally-informed interventions may enhance PGT acceptability and support high-quality decisions. Future directions to surmount PGT disparities may include community health workers and cultural brokers to empower Latinx people to make informed decisions aligned with their values and preferences.

Dataset Information

Genetic Testing Preferences of Individuals in Families with Essential Tremor.

Publications

Genetic Testing Preferences of Individuals in Families with Essential Tremor.

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