Myofibrillar myopathy is a group of hereditary myopathies characterized by myofibrillar dissolution and abnormal intramuscular accumulation of proteins. Here we present 14 Chinese patients with pathologically diagnosed myofibrillar myopathy. Our patients show a male predominance (2.5:1), and the age of onset ranges from childhood to senior (5yr to 67yr) with a median age of 41yr. On physical evaluation, 57.1% patients demonstrate a mixed proximal and distal weakness, 28.6% a predominantly proximal involvement and 14.3% distal. Other common clinical features include joint contracture (35.8%), respiratory insufficiency (28.6%) and paresthesia/hypesthesia (28.6%). Of the 13 patients who underwent electrophysiological evaluation, all show myopathic changes and 78.6% have variable neurogenic changes, the majority of which is consistent with an axonal polyneuropathy with a preferential motor nerve involvement. Next generation sequencing was performed on 13 patients, and 12 were identified to harbor pathogenic mutations in genes including DES, BAG3, FLNC, FHL1 and TTN. Four novel mutations were found in DES, FLNC and FHL1. On muscle pathology, eosinophilic bodies were present in all patients with mutations in DES, BAG3, FHL1 and TTN, but not in the two cases with FLNC mutations. In contrast, patients associated with FLNC tend to demonstrate more rimmed vacuoles than others. The patients with the most rubbed-out fibers were the ones with DES mutations, while those with FLNC mutations did not show any. Abnormal accumulation of desmin was present in all patients, except the ones with FLNC, to a variable extent. It seems that patients with FLNC have a distinctive myopathological picture, ie. the presence of more rimmed vacuoles without eosinophilic bodies. These, together with the absence of abnormal desmin accumulation, make it tantalizing to propose that the patients with FLNC mutations do not share a common etiology with other myofibrillar myopathy cases.