Different Lower Limb Muscle MRI Patterns in Autosomal Dominant Titinopathies

Titin is critical for sarcomere structure and function, and mutations in this gene cause titinopathies, a group of neuromuscular disorders. Muscle MRI is a key tool for diagnosing and understanding these conditions. This study aims to compare the muscle involvement patterns in two autosomal dominant, adult-onset titinopathies: Tibial Muscular Dystrophy (TMD) and Hereditary Myopathy with Early Respiratory Failure (HMERF).

In this multicenter, cross-sectional study, lower limb MRI scans were analyzed for 17 patients with TMD and 15 with HMERF. Clinical and demographic data were collected from medical records. Muscle fat replacement was assessed using a modified Mercuri score for 30 muscles per patient. Two independent evaluators reviewed the images. Heatmaps were used to visualize asymmetry and patterns of fat replacement. Statistical analysis included Cliff's delta and random forests to distinguish muscle involvement between TMD and HMERF, and Spearman's rho to explore correlations between fat replacement and disease duration.

HMERF showed extensive, severe fat replacement, particularly in muscles like the semitendinosus, obturator externus, and gluteus minimus, with distinct intramuscular patterns. In contrast, TMD presented more localized fat replacement, primarily affecting the tibialis anterior and extensor digitorum longus. Both conditions exhibited mixed patterns of muscle replacement and preservation. Random forests confirmed differential muscle involvement, and fat replacement correlated with disease duration more strongly in HMERF than in TMD.

This systematic MRI analysis reveals distinct muscle involvement patterns in TMD and HMERF, providing insights into the differential progression of these titinopathies.