We investigated the frequency, type, and clinical impact of peripheral neuropathy (PN) in myofibrillar myopathies (MFMs) and MFM gene-related myopathies.

MFMs are pathologically-defined hereditary myopathies caused by pathogenic variants in genes encoding Z-disk and chaperone-assisted selective autophagy-related proteins. Mutations in these genes can also cause myopathy without myofibrillar pathology. PN is a known extramuscular manifestation of MFMs.

The Mayo Clinic Clinical Database (January 1993-March 2024) was reviewed to identify patients with pathologically-diagnosed MFM or myopathies due to MFM genes, regardless of myopathological findings. Patients without genetic testing or myopathic manifestation were excluded.

We included 78 patients (44 males), 56 of whom were genetically characterized (23 DES, 10 MYOT, 9 LDB3, 2 FLNC, 2 BAG3, 2 CRYAB, 1 FHL1, and 7 others). PN occurred in 21 patients [13 with axonal large fiber and 8 with small fiber neuropathy], 14 of whom were genetically characterized (5 MYOT, 2 DES, 3 LDB3, 2 BAG3, and 2 CRYAB). PN was less frequent in desminopathy compared to others (p=0.019). The median neuropathy impairment score (NIS) was similar in the PN and non-PN groups (44.0 vs. 35.0; p=0.636). However, the NIS sensory and reflex subscores were significantly higher in the PN group, while motor subscore was comparable. Patients with PN were more likely to be male (76.2% vs. 49.1%; p=0.032), have an older age at myopathy onset (median age 54.4 vs. 36.8 years; p=0.013), use gait aids more frequently (81.0% vs. 54.4%; p=0.032), and have less cardiac involvement (19.0% vs. 43.9%; p=0.044). The prevalence of other PN risk factors, including diabetes mellitus, was comparable between the groups.

Overall, 26.9% of patients with MFM and MFM gene-related myopathies developed PN. PN prevalence varies among genotypes, typically presenting with mild sensory predominance rather than increased muscle weakness, though it may necessitate the use of gait aids.