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Author Credentials

Holly Farkosh Dominika Lozowska MD

Keywords

Genetic testing, neurology, rural, West Virginia

Disciplines

Diseases | Medicine and Health Sciences | Nervous System Diseases

Abstract

Background

Clinicians are increasingly relying on genetic testing to pinpoint definite diagnoses. A more general diagnosis of neuropathy or neuromuscular disease like myopathy can be narrowed down substantially using genetic testing. Because carrier status is of utmost importance in reproductive matters, pathogenic results can prognosticate about future course of the illness and help plan ahead for treatment and social supports. Given the expense of genetic testing, it becomes a cost benefit ratio assessment whether it is worthwhile to collect genetic samples. The purpose of the study was to determine the likelihood of obtaining a conclusive confirmatory diagnosis through genetic testing (measured as % of positive results obtained out of all the submitted samples).

Study Design

Retrospective record review.

Methods

A single clinician’s record of genetic test outcomes was reviewed spanning a 4 year period from July 2015 to June 2019 to identify those who had genetic samples submitted to Invitae, a commercial lab in California which makes genetic test panels available and affordable. The clinician used the typical approach of firstly working up complaints of neuromuscular and neuropathic nature by carrying out a physical exam, drawing labs, doing nerve conductions (NCS), electromyography (EMG) and or muscle biopsy, before sending out for genetic testing. The positive, negative and indeterminate genetic diagnoses were tabulated and the individual disease entities’ prevalence was determined.

Results

96 patients were identified who participated in genetic testing for neuropathic conditions and 59 patients for neuromuscular conditions. The patients’ health records did not have to be mined for results because the clinician’s Invitae account contained de-identified requisition numbers linked to their results . There were about twice as many positive results in the neuromuscular group compared to that of the neuropathic group of patients. There were about three times as many normal results in the neuropathic group compared to the neuromuscular group. Around half of all test samples showed indeterminate results containing variants of unknown significance (VOUS), which were not indicative of any pathology and considered inconclusive.

Conclusions

Based on the study findings, there were 17.7% and 35.6% positive, meaning pathogenic, results respectively among neuropathic and neuromuscular cases sent off for genetic analysis. While 38 out of 155 total cases makes up a small, 24.5% yield of abnormal results, genetic studies are still a worthwhile addition to investigating neuropathic and neuromuscular cases.

Background

Clinicians are increasingly relying on genetic testing to pinpoint definite diagnoses. A more general diagnosis of neuropathy or neuromuscular disease like myopathy can be narrowed down substantially using genetic testing. Because carrier status is of utmost importance in reproductive matters, pathogenic results can prognosticate about future course of the illness and help plan ahead for treatment and social supports. Given the expense of genetic testing, it becomes a cost benefit ratio assessment whether it is worthwhile to collect genetic samples. The purpose of the study was to determine the likelihood of obtaining a conclusive confirmatory diagnosis through genetic testing (measured as % of positive results obtained out of all the submitted samples).

Study Design

Retrospective record review.

Methods

A single clinician’s record of genetic test outcomes was reviewed spanning a 4 year period from July 2015 to June 2019 to identify those who had genetic samples submitted to Invitae, a commercial lab in California which makes genetic test panels available and affordable. The clinician used the typical approach of firstly working up complaints of neuromuscular and neuropathic nature by carrying out a physical exam, drawing labs, doing nerve conductions (NCS), electromyography (EMG) and or muscle biopsy, before sending out for genetic testing. The positive, negative and indeterminate genetic diagnoses were tabulated and the individual disease entities’ prevalence was determined.

Results

96 patients were identified who participated in genetic testing for neuropathic conditions and 59 patients for neuromuscular conditions. The patients’ health records did not have to be mined for results because the clinician’s Invitae account contained de-identified requisition numbers linked to their results . There were about twice as many positive results in the neuromuscular group compared to that of the neuropathic group of patients. There were about three times as many normal results in the neuropathic group compared to the neuromuscular group. Around half of all test samples showed indeterminate results containing variants of unknown significance (VOUS), which were not indicative of any pathology and considered inconclusive.

Conclusion

Based on the study findings, there were 17.7% and 35.6% positive, meaning pathogenic, results respectively among neuropathic and neuromuscular cases sent off for genetic analysis. While 38 out of 155 total cases makes up a small, 24.5% yield of abnormal results, genetic studies are still a worthwhile addition to investigating neuropathic and neuromuscular cases.

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