Utility and yield of genetic testing leading to a definitive neuromuscular or neuropathic diagnosis at a rural outpatient neurology clinic affiliated with a university health center in West Virginia over 4 years.

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

Bethlem myopathy demonstrated in three generations of a rural West Virginia family carrying an autosomal dominant COL6A3 mutation

Mutations in the genes that code for type VI collagen can lead to what are known as the collagenopathies (collagen VI myopathies), such as Bethlem myopathy (BTHLM1), which affect structural tissues like muscles and tendons. We present the case of a young female and her two relatives, who were discovered to share the autosomal dominant COL6A3 mutation and whose presentation in clinic varied from mild to severe. Type VI collagenopathies represent a clinically and genetically heterogeneous spectrum of disorders generally characterized by muscle weakness and joint contractures. We highlight the importance of examining close relatives whenever possible and documenting a pedigree prior to proceeding with further electromyography (EMG) and lab work up, which includes obtaining genetic testing in order to reach a unifying diagnosis. The proband (L.C.) reported challenges with activities of daily living due to distal hand weakness, had significant findings on neuromuscular exam, and had abnormalities on needle EMG testing. Five of her relatives were reported to have weakness and trouble with day-to-day function. Her mother (M.C.) and her maternal grandfather (W.C.) were able to be examined in person and had the condition genetically confirmed

Chronic Exertional Compartment Syndrome: A Case Report about Claudication in a Healthy Adult

Claudication occurs when the blood supply is insufficient to service the musculature in the body with oxygen and metabolic waste management. A clinical complaint of claudication is commonly seen in primary care among older patients with vascular risk factors. A young and healthy patient presenting with claudication is less common and often results in delayed diagnosis with numerous extraneous diagnostic studies. This case discusses a young, healthy male patient with lower extremity symptoms that got worse with exercise and better with rest. He had normal physical exam findings leading to multiple diagnostic studies and over 12 months between the onset of symptoms and his return to full activity. Claudication can result from rare conditions, such as chronic exertional compartment syndrome, popliteal artery entrapment syndrome, fibromuscular dysplasia, and cystic adventitial disease. Symptomatic individuals with chronic exertional compartment syndrome experience reversible muscular pain from exercise-induced pressure, which increases within the finite spaces of any muscular compartment. Understanding the pathophysiology of exertional compartment syndrome and its related diagnoses allows for an organized diagnostic approach to young, healthy patients with claudication symptoms. This organized approach allows timely care, which is imperative for primary care physicians to reduce the number of tests performed, decrease the time to diagnosis, and reduce both the anxiety and cost for the patient. The approach presented herein can serve as a reminder of a proper work-up in similar patients and allow practitioners to identify the conditions that require intervention to improve outcomes