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Benefits of a genetic diagnosis beyond treatment. For many patients and families, a genetic diagnosis has multiple important benefits. A genetic diagnosis can end the diagnostic odyssey, confirm a clinical diagnosis, clarify prognosis, impact family planning, and identify at-risk relatives. Connections with support networks such as family foundations are important sources of advocacy and research

Benefits of a genetic diagnosis beyond treatment. For many patients and families, a genetic diagnosis has multiple important benefits. A genetic diagnosis can end the diagnostic odyssey, confirm a clinical diagnosis, clarify prognosis, impact family planning, and identify at-risk relatives. Connections with support networks such as family foundations are important sources of advocacy and research

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The role of genetic testing in neurologic clinical practice has increased dramatically in recent years, driven by research on genetic causes of neurologic disease and increased availability of genetic sequencing technology. Genetic testing is now indicated for adults with a wide range of common neurologic conditions. The potential clinical impacts...

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... The number of conditions for which genetic testing is indicated, as we understand more about how results influence medical management for patients, is increasing exponentially [1][2][3]. However, only a minority of patients with these conditions receive genetic testing and benefit from the use of genomic medicine [4]. ...
... Oncology specialties have been early adopters of germline genetic testing, and currently the identification of pathogenic variants in high and moderate penetrance cancer predisposition genes leads to critical changes in clinical management, including treatment selection [5,6]. In other specialties, including cardiology, neurology, and endocrinology, the use of genetic testing to guide medical management is quickly being adopted with broad use across multiple diseases [2,[7][8][9][10][11][12][13]. Genetic testing now is recognized as an essential part of clinical care, with payers exhibiting a strong preference in approving coverage of genetic tests that change medical care [14] and patients recognizing the potential benefits of precision medicine [15,16]. ...
... Primary and secondary implementation outcomes, and contextual factors that shape implementation effectiveness (e.g., clinician location, patient demographics) will be captured. Prior to the nudges being sent out, electronic phenotyping algorithms will be used to identify patients for whom genetic testing is recommended based on published guidelines and expert opinion [2,3,7,10]. Conditions were selected for which 1) genetic testing is considered standard of care due to implications for medical management; 2) the genetic testing approach is standardized; and 3) effective electronic phenotyping with a positive predictive value (PPV) [39,86] of over 85% can be performed (Supplemental Table 1). ...
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Background Germline genetic testing is recommended for an increasing number of conditions with underlying genetic etiologies, the results of which impact medical management. However, genetic testing is underutilized in clinics due to system, clinician, and patient level barriers. Behavioral economics provides a framework to create implementation strategies, such as nudges, to address these multi-level barriers and increase the uptake of genetic testing for conditions where the results impact medical management. Methods Patients meeting eligibility for germline genetic testing for a group of conditions will be identified using electronic phenotyping algorithms. A pragmatic, type 3 hybrid cluster randomization study will test nudges to patients and/or clinicians, or neither. Clinicians who receive nudges will be prompted to either refer their patient to genetics or order genetic testing themselves. We will use rapid cycle approaches informed by clinician and patient experiences, health equity, and behavioral economics to optimize these nudges before trial initiation. The primary implementation outcome is uptake of germline genetic testing for the pre-selected health conditions. Patient data collected through the electronic health record (e.g. demographics, geocoded address) will be examined as moderators of the effect of nudges. Discussion This study will be one of the first randomized trials to examine the effects of patient- and clinician-directed nudges informed by behavioral economics on uptake of genetic testing. The pragmatic design will facilitate a large and diverse patient sample, allow for the assessment of genetic testing uptake, and provide comparison of the effect of different nudge combinations. This trial also involves optimization of patient identification, test selection, ordering, and result reporting in an electronic health record-based infrastructure to further address clinician-level barriers to utilizing genomic medicine. The findings may help determine the impact of low-cost, sustainable implementation strategies that can be integrated into health care systems to improve the use of genomic medicine. Trial registration ClinicalTrials.gov. NCT06377033. Registered on March 31, 2024. https://clinicaltrials.gov/study/NCT06377033?term=NCT06377033&rank=1
... As the cost of sequencing continues to fall, this too is likely to shift in the future [52]. While GS may be more expensive, this test should be prioritized over ES when conditions on the differential are associated with variants not detectable on ES, such as repeat expansion disorders; recommendations for test selection have been described elsewhere [53]. In addition to the barrier of cost, there also exists a barrier in the form of personnel: not all clinics for adults with NMDs will have a genetic counselor or clinician with genetics expertise on staff. ...
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Advances in gene-specific therapeutics for patients with neuromuscular disorders (NMDs) have brought increased attention to the importance of genetic diagnosis. Genetic testing practices vary among adult neuromuscular clinics, with multi-gene panel testing currently being the most common approach; follow-up testing using broad-based methods, such as exome or genome sequencing, is less consistently offered. Here, we use five case examples to illustrate the unique ability of broad-based testing to improve diagnostic yield, resulting in identification of SORD-neuropathy, HADHB-related disease, ATXN2-ALS, MECP2 related progressive gait decline and spasticity, and DNMT1-related cerebellar ataxia, deafness, narcolepsy, and hereditary sensory neuropathy type 1E. We describe in each case the technological advantages that enabled identification of the causal gene, and the resultant clinical and personal implications for the patient, demonstrating the importance of offering exome or genome sequencing to adults with NMDs.
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Careful evaluation of symptom progression and radiographic findings are essential tools when approaching cases of suspected chronic myelopathies. In this case, a 26-year-old woman presented with progressive ambulatory and bladder dysfunction for 4 years. Her examination was marked by bilateral lower-extremity upper motor neuron signs and distal large-fiber sensory loss. Neurologic workup for acquired causes of this presentation was unrevealing. MRI of the brain revealed a characteristic radiologic finding. Guided genetic testing ultimately yielded the final diagnosis. In this clinical vignette, we review the approach to chronic myelopathy including consideration of genetic etiologies and pursuit of targeted gene testing. We further discuss the typical clinical and radiographic findings of a rare diagnosis.