A mutation in the filamin c gene causes myofibrillar myopathy with lower motor neuron syndrome: a case report

Abstract

Background: Myofibrillar myopathies (MFMs) are a genetically heterogeneous group of muscle disorders. Mutations in the filamin C gene (FLNC) have previously been identified in patients with MFM. The phenotypes of FLNC-related MFM are heterogeneous.

Case presentation: The patient was a 37-year-old male who first experienced weakness in the distal muscles of his hand, which eventually spread to the lower limbs and proximal muscles. Serum creatine kinase levels were moderately elevated. Obvious neuropathic changes in the electromyographic exam and edema changes in lower distal limb magnetic resonance imaging were observed. Histopathological examination revealed the presence of abnormal protein aggregates and angular atrophy in some muscle fibers. Ultrastructural analysis showed inordinate myofibrillar structures and dissolved myofilaments. DNA sequencing analysis detected a heterozygous missense mutation (c.7123G > A, p.V2375I) in the immunoglobulin (Ig)-like domain 21 of FLNC.

Conclusions: FLNC mutation c.7123G > A, p.V2375I in the immunoglobulin (Ig)-like domain 21 can be associated with distal myopathy with typical MFM features and lower motor neuron syndrome. Although electromyographic examination of our patient showed obvious neuropathic changes, MFM could not be excluded. Therefore, genetic testing is necessary to make an accurate diagnosis.

Keywords: Distal myopathy; Filamin C gene; Lower motor neuron; Missense mutation; Myofibrillar myopathy.

Fig. 1

Clinical pattern of the patient. Distal limb weakness affecting both upper and lower extremities, with conspicuous muscle atrophy were seen (a: gastrocnemius and anterior tibial muscles, b: interosseus muscles of the hand)

Fig. 2

Transverse T2-weighted and TIRM sequence muscle magnetic resonance images. A slightly increased signal was detected in the posterior compartment of the thigh, in the semimembranosus and semitendinosus muscles (a: T2-weighted, b: TIRM). A highly increased signal intensity in TIRM sequences was detected at the level of the lower leg, indicating obvious muscular edema (d). A mild increase in the signal intensity was observed in the T2 sequence of soleus and tibialis anterior muscles, indicating fat replacement (c)

Fig. 3

Histopathological examination of the skeletal muscles. a: HE staining showing muscle fibers of variable sizes, abnormal material deposits (white arrow), and angular atrophic fibers (red arrow). b: MGT staining showing purple myofibrillary inclusions. c: NADH-TR staining showing reduced oxidative enzyme activities in some fibers, visible as core-like lesions (red arrow). d: Immunohistochemistry staining with an anti-FLNC antibody revealing immunoreactive deposits at both subsarcolemmal and sarcoplasmic levels. e: Ultrastructural analysis of a muscle fiber showing myofibrillar disorganization (arrows) and submuscular lipofuscin deposition (star). Magnification, × 5000

Fig. 4

Molecular consequences of the FLNC c.7123G > A, p.V2375I mutation. The mutation is located in the 21st Ig-like repeated domain (a). DNA sequencing analysis showed a heterozygous missense mutation (c.7123G > A) in FLNC (red arrows) (b). Partial amino acid sequence alignment of the 21st Ig-like repeat domain of filamin proteins from various species (c)