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

Area of Science:

• Neurology
• Genetics
• Medical Imaging

Background:

• Biallelic pathogenic variants in TTN cause rare, early-onset myopathies with variable muscle weakness, respiratory issues, and potential cardiomyopathy.
• The large size of the TTN gene and diverse phenotypes complicate variant interpretation in TTN-related myopathy (TTN-RM).
• Diagnostic challenges necessitate identifying reliable imaging biomarkers for TTN-RM.

Purpose of the Study:

• To evaluate specific upper extremity muscle ultrasound patterns in patients with biallelic TTN-RM.
• To identify imaging features that can assist in the diagnostic process for TTN-RM.
• To correlate imaging findings with TTN gene variants.

Main Methods:

• Muscle ultrasound was performed on 30 patients with confirmed biallelic TTN-RM (ages 2-47).
• Retrospective analysis of ultrasound images by two independent raters.
• Triceps brachii heads were graded using a modified Heckmatt scale; biceps brachii images were analyzed for a layering pattern.

Main Results:

• Eleven patients showed maximal triceps head involvement on ultrasound.
• Among the remaining 19 patients, 15/19 had higher Heckmatt scores in the triceps long head compared to lateral and medial heads.
• Biceps brachii ultrasound revealed increased echogenicity in the deeper muscle portions.

Conclusions:

• Upper extremity muscle ultrasound demonstrates suggestive patterns in TTN-RM.
• Characteristic triceps involvement and biceps brachii appearance are identified.
• These "TTN compatible imaging phenomena" can aid variant interpretation and diagnosis of TTN-RM.