Case Report: Late Onset Myofibrillary Myopathy in a Patient with DES and LDB3 Mutations
Arnaud Batchou1, Mehwish Khan2, Umair Ahmed3, Edward Yu4
1Northwell, 2Northwell- SIUH, 3Feinstein Institute for Medical Research, 4Northwell Health
Objective:
To report a rare case of a 73-year-old presenting with distal extremity weakness and diagnosed with myofibrillar myopathy via the identification of two disease causing mutations in the genes – DES and ZASP/LDB3
Background:
Myofibrillar myopathies (MFM) refers to a group of rare distal myopathies caused by a heterogenous set of genetic mutations that encode proteins associated with the Z-disc. These conditions are characterized by abnormal protein aggregations and myofibrillar disintegrations. To date, few disease-causing mutations in genes have been identified, including autosomal dominant Desmin (DES) and Z-band alternatively spliced PDZ – motif containing protein (ZASP/LDB3). DES is an intermediate filament present in smooth, cardiac and skeletal muscles and plays a crucial role in the structural integrity of these muscles. ZASP is a Z-disk associated protein found in cardiac and skeletal muscles and though its functions is not well understood, it directly interacts with actin filaments.
Results:
We present a 73-year-old woman with history of primary biliary cirrhosis and lumbar stenosis status post decompression with slowly progressive difficulty ambulating since her early 40s. The patient was found to have bilateral distal lower weakness with steppage gait with proximal upper extremities weakness of less severity. Electrodiagnostic testing and muscle biopsy showed features of neuropathy and myopathy without inflammation. Distal myopathic process was suspected, thus, genetic testing was sent and later revealed autosomal dominant heterozygous mutations in both the DES (c.407T>A) and ZASP (c.652C>T) genes, thereby confirming the diagnosis of myofibrillar myopathy.
Conclusions:
We describe a patient with distal myopathy found to have heterozygous inheritance pattern of two genes known to be associated with myofibrillar myopathy, suggesting a possible polygenic etiology with point mutations in DES and ZASP previously not known to be pathogenic.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.