54VP Emerging muscle ultrasound patterns as a diagnostic aid in TTN-related myopathy

• Published in: Neuromuscular disorders : NMD 2024-10, Vol.43, p.104441, Article 104441.252
• Main Authors: Potticary, A., McAnally, M., Donkervoort, S., Bönnemann, C.
• Format: Article
• Language: English
• ISSN: 0960-8966
• DOI: 10.1016/j.nmd.2024.07.261

Variants in TTN, the gene encoding the titin protein, are known to cause rare forms of congenital myopathy manifesting with variable severity and progression of muscle weakness, contractures, and cardiomyopathy. Muscle ultrasound is a highly sensitive, real-time imaging tool easily performed at bedside, used to visualize myopathic changes in the muscle. We demonstrate how muscle ultrasound can be a complementary diagnostic tool, identifying distinctive findings in the triceps and biceps brachii in TTN-related myopathy. 30 individuals with confirmed biallelic TTN-related myopathy were evaluated under an approved natural history study at the NIH (16 M, 14 F; ages 6 months – 47 years old). Muscle ultrasound was performed at every visit, with serial studies in 7 patients, yielding 46 total studies. Two independent raters graded each of the three triceps brachii heads (lateral, medial, long) using the modified Heckmatt scale, a semi-quantitative score (0-3), and interrater reliability was determined using weighted Cohen's Kappa (κ=0.97). 18 studies demonstrated maximum involvement, as capturable on ultrasound, of all three heads of the triceps. Excluding these studies, 20/28 ultrasound studies yielded a greater modified Heckmatt score in the long head compared to the lateral and medial heads of the triceps, indicating selective involvement. Analysis of biceps ultrasound images also revealed a distinctive layering pattern, specifically greater increased echogenicity in the lower layer of the biceps, in 17 of the 46 studies. 8/17 of these studies demonstrated equal severity of biceps and triceps long head involvement. Here we present an analysis of upper extremity muscle ultrasound findings in patients with biallelic TTN-related myopathy, revealing a consistent pattern of triceps involvement and characteristic appearance of the biceps brachii. These “TTN compatible features” could aid in variant interpretation and help substantiate a diagnosis of TTN-related myopathy.