Interindividual variability of muscle involvement on imaging in a family with FLNC c.577G>A (p.A193T)-related myopathy.

FLNC-related myopathy (FLNC-RM) with actin-binding domain (ABD) variants is known to show heterogeneous muscle involvement; however, whether such variability exists within families sharing the same variant, and which muscles contribute to this heterogeneity, remain unclear. We investigated muscle involvement patterns in four members of a single family carrying the FLNC c.577G>A (p.A193T) variant who underwent serial longitudinal muscle imaging. A five-point semi-quantitative visual assessment of fatty replacement was performed across 43 muscles using whole-body CT and MRI, covering the shoulder, trunk, pelvis, thighs, and lower legs. Uniform manifold approximation and projection (UMAP) provided a visualization in which longitudinal observations tended to group by individual. In the original 43-dimensional mMS matrix, the mean within-patient distance was smaller than the mean between-patient distance among P1a-c (3.58 vs. 7.29; exact permutation P = 0.00017), supporting the persistence of individual-specific mMS distribution profiles over the observed period. Analysis across muscles identified a subset-gluteus medius, gluteus minimus, adductor magnus, semimembranosus, gastrocnemius (medial and lateral heads), and soleus-for which mMS showed a strong fit to age-based models, while many other muscles showed marked interindividual variability. Chronological data further illustrated common and variable patterns of muscle involvement while preserving individual differences. Notably, relative preservation of the tibialis anterior and extensor digitorum longus was observed even at advanced stages. Overall, these findings indicate that FLNC-RM with the ABD variant, particularly the c.577G>A, is characterized by marked interindividual variability in muscle involvement patterns, even among members of the same family.