Title: LDB3/ZASP-related myofibrillar myopathy associated with marked phenotypic variability
Abstract: Myofibrillar myopathy (MFM) is a rare inherited myopathy characterized by slowly progressive muscle weakness, and may present with life-threatening cardiomyopathies and respiratory failure. Mutations in DES, CRYAB, MYOT, LDB3/ZASP, FLNC, BAG3 and FHL1 lead to dysfunction through Z-disk and myofibril disintegration, followed by abnormal accumulation of intracellular proteins. This report outlines the clinical presentation/muscle biopsy in a LDB3 myopathy family with four affected members with significant phenotypic variability. This case study involved four affected family members (1 mother and 3 adult children) who with myopathy and underwent myofibrillar myopathy genetic testing. Muscle biopsy with electron microscopy was performed on three patients. The proband (mother) presented at age 58 with adult-onset progressive proximal myopathy and was diagnosed with polymyositis. Three of the patient's adult children presented with onset ranging from severe proximal and distal myopathy to asymptomatic toe extension weakness. Muscle biopsy of two of the proband's children demonstrated intranuclear rods, sarcoplasmic protein aggregates, rimmed vacuoles, and necrotic fibers. This proband's muscle biopsy was reviewed and also showed inflammatory cells, nuclear rods and rimmed vacuoles. The original nemaline rod myopathy genetic panel (ACTA1, TPM2, TPM3, NEB, TNTT1, KBTBD13, CFL2) was negative in one affected members. Genetic testing revealed a heterozygous mutation in the LDB3 gene on exon 6 (c.784G > A; p.Ala262Thr) in 3 of the affected patients that was not present in an unaffected brother. Cardiac testing is currently normal. LDB3 mutations can present with a wide clinical spectrum. Misdiagnosis of genetic myopathies as inflammatory can lead to unnecessary/harmful immunosuppressant therapy. Identifying these genetic myopathies is essential to provide appropriate treatment and screen for life-threatening cardiac/respiratory complications.
Publication Year: 2016
Publication Date: 2016-10-01
Language: en
Type: article
Indexed In: ['crossref']
Access and Citation
Cited By Count: 2
AI Researcher Chatbot
Get quick answers to your questions about the article from our AI researcher chatbot