Disparate and shared transcriptomic signatures associated with cortical atrophy in genetic bvFTD.

Cortical atrophy in behavioral variant frontotemporal degeneration (bvFTD) exhibits spatial heterogeneity across genetic subgroups, potentially driven by distinct biological mechanisms. Using an integrative imaging-transcriptomics approach, we identified disparate and shared transcriptomic signatures associated with cortical thickness in , or -related bvFTD. Genes associated with cortical thinning in -bvFTD were implicated in neurotransmission, further supported by mapping synaptic density maps to cortical thickness maps.

Expanding Genetic Counselor Roles: A Model for Global Research Development.

Purpose: Genetic counselors (GCs) increasingly play key roles in advancing genomic medicine through innovative research. Here, we examine one large cohort of GCs' evolving contributions to the literature, with the goal of facilitating worldwide professional development for GCs through scholarly activities.

Methods: Publications were cataloged by members of the Section of Genetic Counseling (Section), established at the Children's Hospital of Philadelphia and the University of Pennsylvania in 2014, including publication year, journal, impact factor, and author position.

The Miami Framework for ALS and related neurodegenerative disorders: an integrated view of phenotype and biology.

Increasing appreciation of the phenotypic and biological overlap between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, alongside evolving biomarker evidence for a pre-symptomatic stage of disease and observations that this stage of disease might not always be clinically silent, is challenging traditional views of these disorders. These advances have highlighted the need to adapt ingrained notions of these clinical syndromes to include both the full phenotypic continuum - from clinically silent, to prodromal, to clinically manifest - and the expanded phenotypic spectrum that includes ALS, frontotemporal dementia and some movement disorders. The updated clinical paradigms should also align with our understanding of the biology of these disorders, reflected in measurable biomarkers.

repeat expansions modify risk for secondary motor and cognitive-behavioral symptoms in behavioral-variant frontotemporal degeneration and amyotrophic lateral sclerosis.

In behavioral-variant frontotemporal degeneration (bvFTD) and amyotrophic lateral sclerosis (ALS), secondary motor or cognitive-behavioral symptoms, respectively, are associated with shorter survival. However, factors influencing secondary symptom development remain largely unexplored. We performed a retrospective evaluation of the entire disease course of individuals with ALS (n=172) and bvFTD (n=69).

Disparities in Genetic Testing for Neurologic Disorders.

Background And Objectives: Genetic testing is now the standard of care for many neurologic conditions. Health care disparities are unfortunately widespread in the US health care system, but disparities in the utilization of genetic testing for neurologic conditions have not been studied. We tested the hypothesis that access to and results of genetic testing vary according to race, ethnicity, sex, socioeconomic status, and insurance status for adults with neurologic conditions.

The Importance of Offering Exome or Genome Sequencing in Adult Neuromuscular Clinics.

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 neuropathy, -related disease, -ALS, related progressive gait decline and spasticity, and -related cerebellar ataxia, deafness, narcolepsy, and hereditary sensory neuropathy type 1E.

Changes in Digital Speech Measures in Asymptomatic Carriers of Pathogenic Variants Associated With Frontotemporal Degeneration.

Background And Objectives: Clinical trials developing therapeutics for frontotemporal degeneration (FTD) focus on pathogenic variant carriers at preclinical stages. Objective, quantitative clinical assessment tools are needed to track stability and delayed disease onset. Natural speech can serve as an accessible, cost-effective assessment tool.

Incorporating Genetic Testing Into the Care of Patients With Amyotrophic Lateral Sclerosis/Frontotemporal Degeneration Spectrum Disorders.

Purpose Of Review: Amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) spectrum disorders have a strong genetic component. Genetic counselors are a limited resource, and therefore, other providers must be prepared to integrate genetic testing into their practice.

Recent Findings: Recent ALS/FTD studies have demonstrated that lack of family history does not preclude a genetic etiology.

Preimplantation Genetic Testing for Adult-Onset Neurodegenerative Disease: Considerations for Access, Utilization, and Counseling.

Preimplantation genetic testing for monogenic conditions (PGT-M), formerly called preimplantation genetic diagnosis, is a specialized assisted reproduction technique that aims to reduce the risk of a pregnancy inheriting a monogenic condition. Despite calls to increase awareness and prepare neurologists for discussing PGT-M with patients and their families, no guidelines currently exist. When introducing PGT-M to those who may be interested in using it, there are major factors for discussion, including (1) genetic considerations (e.

The lived experience of reconstructing identity in response to genetic risk of frontotemporal degeneration and amyotrophic lateral sclerosis.

With the increasing availability of predictive genetic testing for adult-onset neurodegenerative conditions, it is imperative that we better understand the impact of learning one's risk status. Frontotemporal degeneration (FTD) is the second most prevalent cause of early-onset dementia. About one-third of patients have an identifiable genetic etiology, and some genetic variants that cause FTD can also cause amyotrophic lateral sclerosis (ALS).

Evaluation of an educational conference for persons affected by hereditary frontotemporal degeneration and amyotrophic lateral sclerosis.

Objective: There are limited studies exploring the support and education needs of individuals at-risk for or diagnosed with hereditary frontotemporal degeneration (FTD) and/or amyotrophic lateral sclerosis (ALS). This study evaluated a novel conference for this population to assess conference efficacy, probe how participants assessed relevant resources, and identify outstanding needs of persons at-risk/diagnosed.

Methods: We implemented a post-conference electronic survey that probed participants' satisfaction, prior experience with resources, and unmet needs.

Isoform-specific patterns of tau burden and neuronal degeneration in MAPT-associated frontotemporal lobar degeneration.

Frontotemporal lobar degeneration with MAPT pathogenic variants (FTLD-MAPT) has heterogeneous tau pathological inclusions postmortem, consisting of three-repeat (3R) or four-repeat (4R) tau isoforms, or a combination (3R + 4R). Here, we studied grey matter tau burden, its relation to neuronal degeneration, and regional patterns of pathology in different isoform groups of FTLD-MAPT. We included 38 FTLD-MAPT autopsy cases with 10 different MAPT pathogenic variants, grouped based on predominant tau isoform(s).

Transitioning to telegenetics in the COVID-19 era: Patient satisfaction with remote genetic counseling in adult neurology.

The COVID-19 pandemic rapidly changed genetic counseling services across the United States. At the University of Pennsylvania (UPenn), a large academic hospital in an urban setting, nearly all genetic counseling (GC) visits for adult-onset disorders within the Department of Neurology were conducted via secure videoconferencing (telegenetics) or telephone between March and December 2020. Although telemedicine services have been steadily emerging, many clinical programs, including the neurogenetics program at UPenn, had not built infrastructure or widely utilized these services prior to the pandemic.

Neocortical origin and progression of gray matter atrophy in nonamnestic Alzheimer's disease.

Amnestic Alzheimer's disease (AD) is characterized by early atrophy of the hippocampus and medial temporal lobes before spreading to the neocortex. In contrast, nonamnestic Alzheimer's patients have relative sparing of the hippocampus, but the pattern in which the disease spreads is unclear. We examined spreading disease in nonamnestic AD using a novel magnetic resonance imaging-based analysis adapted from pathologic staging studies, applied here to cross-sectional imaging data.