Temporal trends and yield of clinical diagnostic genetic testing in adult neurology

Abstract

While genetics evaluation is increasingly utilized in adult neurology patients, its usage and efficacy are not well characterized. Here, we report our experience with 1461 consecutive patients evaluated in an adult neurogenetics clinic at a large academic medical center between January 2015 and March 2020. Of the 1461 patients evaluated, 1215 patients were referred for the purposes of identifying a genetic diagnosis for an undiagnosed condition, 90.5% of whom underwent genetic testing. The modalities of genetic testing utilized varied across referral diagnostic categories, including a range of utilization of whole exome sequencing (WES) as an initial test in 13.9% of neuromuscular patients to 52.9% in white matter disorder patients. The usage of WES increased over time, from 7.7% of initial testing in 2015 to a peak of 27.3% in 2019. Overall, genetic testing yielded a causal genetic diagnosis in 30.7% of patients. This yield was higher in certain referring diagnosis categories, such as neuromuscular (39.0%) and epilepsy (29.8%). Our study demonstrates that evaluation at an adult neurogenetics referral center can yield diagnoses in a substantial fraction of patients. Additional research will be needed to determine optimal genetic testing strategies and cost effectiveness of adult neurogenetics evaluation.

Diagnostic yield of clinical exome sequencing in adulthood in medical genetics clinics

“…Fourteen variants of unknown significance in There are a small number of studies using ES (research or clinical) in adults which are summarized in Table S5. The diagnostic yield ranged from 17% to 60% with a wide range of phenotypes in those studies (da Graça et al, 2022;Guo et al, 2021;Minardi et al, 2020;Mu et al, 2019;Posey et al, 2016;Sabo et al, 2020;Shickh et al, 2021).…”

“…There are a small number of studies using ES (research or clinical) in adults which are summarized in Table S5. The diagnostic yield ranged from 17% to 60% with a wide range of phenotypes in those studies (da Graça et al, 2022; Guo et al, 2021; Minardi et al, 2020; Mu et al, 2019; Posey et al, 2016; Sabo et al, 2020; Shickh et al, 2021). Neurogenetic phenotypes such as intellectual disability (Sabo et al, 2020), epileptic encephalopathy (Minardi et al, 2020), ataxia (da Graça et al, 2022), and neuromuscular disorders (Guo et al, 2021) reach a higher diagnostic yield of ES.…”

“…However, there are only a small number of studies applying ES in the adult population in individuals suspected of having an underlying genetic disease. Adult ES studies have been reported for different clinical phenotypes such as ataxia, stroke, epilepsy, and intellectual disability in neurology clinics (Bardakjian et al, 2018; da Graça et al, 2022; Guo et al, 2021; Ilinca et al, 2020; Minardi et al, 2020; Pierce et al, 2019; Sabo et al, 2020; Snoeijen‐Schouwenaars et al, 2019).…”

O Que Sabemos Sobre Genética Em Epilepsia: Uma Revisão

“…22 A análise desse e outros estudos levantam o questionamento quanto à custo-efetividade de investigações como essa. 23 A ocorrência de "clusters" familiares onde vários indivíduos apresentam manifestação similar foi descrita em 303 famílias com mais de três pessoas acometidas por epilepsias "comuns" (não graves) em um consórcio multicêntrico. 24 Possivelmente a testagem genética e a farmacogenômica serão mais acessíveis no futuro e poderão ser importantes armas para determinar a etiologia, especialmente em casos de encefalopatia epiléptica e indivíduos selecionados, onde poderá influenciar não somente no aconselhamento genético, mas também na escolha do tratamento mais adequado para cada um.…”

Genetic diagnosis for adult patients at a genetic clinic

“…The overall diagnostic yield for molecular genetics was only 12-22% in adult patients, versus 25-55% in children (Yang et al 2014;Posey et al 2016). In the studies of adult patients with specific symptoms such as neurogenic diseases or cerebellar ataxia, the detection rate was higher (28-32%) (Bardakjian et al 2018;Coutelier et al 2018;Guo et al 2021;Mergnac et al 2022;Sainio et al 2022) than in chronic kidney diseases (12-17%) (de Haan et al 2019). Genetic testing for intellectual disability or congenital anomalies have been confirmed beneficial in children (Malinowski et al 2020), and have been given a strong recommendation as first or second tier investigations in these pediatric patients by The American College of Medical Genetics and Genomics (Manickam et al 2021).…”