Emerging Upper Extremity Muscle Ultrasound Patterns as a Diagnostic Aid in TTN-Related Myopathies

Biallelic pathogenic variants in TTN cause rare forms of early-onset myopathy, manifesting with variable severity, distribution, and progression of muscle weakness, often associated with respiratory insufficiency and potentially cardiomyopathy. The large size of TTN and phenotypic heterogeneity in TTN-related myopathy (TTN-RM) makes variant interpretation challenging. Here, we aim to evaluate suggestive imaging patterns of differential muscle involvement in the upper extremities in patients with biallelic TTN-RM that can aid in the diagnostic process.

Thirty patients with confirmed biallelic TTN-related myopathy were evaluated by muscle ultrasound during the study visit (16 males, 14 females; ages 2-47 years). Study images were reviewed retrospectively for this analysis. Two independent raters graded each of the triceps brachii heads using a modified Heckmatt scale. Biceps images were analyzed semi-quantitatively for a layering pattern.

Eleven patients demonstrated maximum involvement, as capturable on ultrasound, of all the triceps heads. Excluding these, 15/19 patients demonstrated a greater modified Heckmatt score in the long head compared to the lateral and medial heads of the triceps. Analysis of biceps images revealed greater increased echogenicity in the deeper portion of the biceps brachii muscle.

We present an analysis of upper extremity muscle ultrasound findings in patients with biallelic TTN-related myopathy, revealing a suggestive pattern of triceps involvement and characteristic appearance of the biceps brachii. These "TTN compatible imaging phenomena" will aid in variant interpretation and help substantiate a diagnosis of TTN-related myopathy.