Reducing Body Myopathy in Female Patients With FHL1 Variants Showing Rapid and Severe Evolution Mimicking Inflammatory Myopathy

Figures

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  Figure 1. Motor and Respiratory Function Evolution (A) Motor function evolution. Each patient is identified with a different color. The slope of the curve is proportional to the rate of clinical progression. The horizontal red line represents the threshold corresponding to loss of ambulation. (B) Evolution of respiratory function. Green and blue circles mark age at loss of ambulation in patients P3 and P4, respectively. Red squares mark the age at which noninvasive ventilation (NIV) was started.

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  Figure 2. Main Myopathologic Features The main myopathologic features of P1 (A, B, E, F, and G) and P2 (C, D, H, I, and J). HE: eosinophilic cytoplasmic aggregates (black arrowheads) (A, C). Menadione α-glycerophosphate: reactive protein material in a cluster of fibers (B, D). Immunofluorescence studies showing desmin aggregates (E, H) and perinuclear FHL1 aggregates (F, I). Merged channels (G, J)

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  Figure 3. Ultrastructural Myopathologic Features EM: electron microscopy. P1 (A, B and C) and P5 (D, E, and F). Reducing bodies surrounding nuclei (A) and lipid droplets (B). (C) Marked sarcomere disorganization. (D, E) Reducing bodies inside protein aggregates. (F) Reducing bodies influencing sarcomere organization. Yellow arrows indicate reducing bodies in all images.

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  Figure 4. Asymmetric Involvement in Muscle MRI Whole-body muscle MRI, T1-weigthed and STIR sequences, axial plane. The green dotted line indicates the spared muscles, compared with the opposite side. Muscle presenting a severe or complete fibro-fatty replacement (Mercuri 3 and 4) are indicate with the red star. Yellow arrow head points muscle showing STIR hypersignal.

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  Figure 5. Pathogenic Variants (A) schematic representation of FHL1 protein. The blue box indicates the region of the protein that contains all the variants. (B) 3D representation of variant localization on FHL1 protein (C) Variant localization according to domain. Predicted 3-dimensional structure of protein FHL1 obtained from the AlphaFold database (alphafold.ebi.ac.uk/).