Abstract Details

Title Genetic Testing - Muddying the Water for Diagnosis of Inflammatory Myopathies

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 12-009

Objective NA

Background Inclusion body myositis (IBM) is an inflammatory myopathy that has a unique pattern of weakness with proximal lower extremity and distal upper extremity involvement. IBM typically does not include significant restrictive lung disease (RLD) or cardiac involvement. Diagnosis is typically made by clinical exam and muscle biopsy. Genetic panels are increasingly used to screen for genetic myopathies. These tests assess genes of interest but also include potentially hundreds of other genes that may return variants of unknown significance (VUS). Genetic testing has become more commonly used for diagnosis of myopathies, but, the presence of less well characterized genetic variants can confuse the diagnostic picture.

Design/Methods NA

Results A 70-year-old male presented with asymmetric proximal lower extremity and distal upper extremity, finger flexor, weakness. Creatine phosphokinase was 195. Muscle biopsy was obtained in 2016, which revealed myofiber size variation with occasional rimmed vacuoles and positive TDP-43 cytoplasmic aggregates suggestive of IBM. As his disease progressed, he developed restrictive lung disease and cardiac conduction block which is less typical of IBM. NT5C1A antibodies were negative. Next generation sequencing revealed VUS in the RYR1 and LDB3 genes, which have been associated with central core (and other structural myopathies) and myofibrillar myopathy, respectively. No genetic variants were identified in the VCP or GNE genes. Second opinion pathology review with special staining of the muscle tissue did not reveal evidence of RYR1-related or myofibrillar myopathies. Additional staining did show MHC class I expression on myofibers and complement deposition consistent with an inflammatory myopathy such as IBM.

Conclusions Genetic testing can be a useful tool to pinpoint the diagnosis of many neuromuscular conditions. However, it does not always reveal the whole picture and, at times, can complicate diagnosis, leading clinicians down the wrong diagnostic path. Clinical examination and muscle biopsy remain important diagnostic tools for disease confirmation.

Authors/Disclosures
Marc J. Van De Rijn, MD (spaulding Rehabilitation Hospital) PRESENTER	No disclosure on file
	No disclosure on file
Erik K. Henricson, MPH (University of California Davis)	No disclosure on file
	No disclosure on file

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