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

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

Angiogram negative subarachnoid hemorrhage in the setting of sexual intercourse and chronic cannabis use

Etiology of unprovoked subarachnoid hemorrhage (SAH) is predominantly from cerebral aneurysm rupture and manifests classically as a thunderclap headache. Orgasmic cephalgia may herald SAH given that 4-12% of SAH sufferers were found to have engaged in prior sexual activity.(1) Precipitating causes of SAH leading to aneurysmal rupture may be the rise in blood pressure caused by physical activity. A conventional angiogram (CTA) is used to reveal a source of the bleed and but occasionally this is normal, and is labelled angiogram-negative SAH or non-aneurysmal SAH. In those cases digital subtraction imaging (DSA) is needed for verification. Herein we discuss an instance of angiogram negative SAH which occurred after sexual activity in a young male with a chronic cannabis habit

Diagnosis of a Centronuclear Myopathy Case in Appalachia 20 Years from Symptom Onset.

Dynamin 2 (DMN2) mutations cause centronuclear myopathy (CNM) and Charcot Marie Tooth (CMT). Herein we discuss the details of a patient\u27s case of adult onset CNM. We also highlight the unique features of this case with regards to the importance of electromyography (EMG), muscle biopsy and genetic testing in identifying CNM, as well as potential for improving outcomes by having a high index or suspicion and emphasizing better access to healthcare in underserved areas

Bilateral foot drop linked to rapid intentional weight loss and long distance walking.

There are many causes of acute onset foot drop ranging from deep fibular nerve or sciatic nerve injury caused by trauma or a compressive mass such as a neuroma, to spinal cord disorders like disc herniation causing L4-5 radiculopathy, and various muscular dystrophies affecting the tibialis anterior muscle responsible for foot dorsiflexion and eversion. Even brain disorders like MS, stroke or ALS can result in foot drop. We present a case of bilateral foot drop as a complication of rapid 70 lb weight loss which was described in literature previously as “slimmer’s palsy”

Statin Autoimmune Necrotizing Myopathy Diagnosed After a Motor Vehicle Accident

One of the most commonly prescribed lipid lowering medications are statins. In most cases, statins are well tolerated. In rare instances, statin induced necrotizing autoimmune myositis (SINAM) can occur. The following case presents a patient with a 15 year history of simvastatin use who developed SINAM following a motor vehicle accident

Diagnosis of a Centronuclear Myopathy Case in Appalachia 20 Years from Symptom Onset

Dynamin 2 (DMN2) mutations cause centronuclear myopathy (CNM) and Charcot Marie Tooth (CMT). Herein we discuss the details of a patient's case of adult onset CNM. We also highlight the unique features of this case with regards to the importance of electromyography (EMG), muscle biopsy and genetic testing in identifying CNM, as well as potential for improving outcomes by having a high index or suspicion and emphasizing better access to healthcare in underserved areas