Different Lower Limb Muscle MRI Patterns in Autosomal Dominant Titinopathies.

Area of Science:

• Neuromuscular disorders
• Genetics and molecular biology
• Medical imaging

Background:

• Mutations in the titin gene cause titinopathies, a group of neuromuscular disorders affecting sarcomere structure and function.
• Muscle Magnetic Resonance Imaging (MRI) is crucial for diagnosing and understanding titinopathies.
• Tibial Muscular Dystrophy (TMD) and Hereditary Myopathy with Early Respiratory Failure (HMERF) are distinct autosomal dominant, adult-onset titinopathies.

Purpose of the Study:

• To compare the muscle involvement patterns in TMD and HMERF using lower limb MRI.
• To identify differential patterns of muscle fat replacement between TMD and HMERF.
• To correlate MRI findings with disease duration.

Main Methods:

• A multicenter, cross-sectional study analyzed lower limb MRI scans from 17 TMD and 15 HMERF patients.
• Muscle fat replacement was quantified using a modified Mercuri score across 30 muscles per patient.
• Statistical analyses, including random forests and Cliff's delta, were employed to differentiate muscle involvement patterns and assess correlations.

Main Results:

• HMERF exhibited extensive fat replacement in specific muscles (semitendinosus, obturator externus, gluteus minimus) with unique intramuscular patterns.
• TMD showed more localized fat replacement, primarily affecting the tibialis anterior and extensor digitorum longus.
• Differential muscle involvement between TMD and HMERF was confirmed, with fat replacement correlating more strongly with disease duration in HMERF.

Conclusions:

• Systematic MRI analysis demonstrates distinct muscle involvement patterns in TMD and HMERF.
• These findings offer valuable insights into the differential diagnosis and progression of these titinopathies.
• Muscle MRI serves as a key tool for characterizing titinopathies.