Taking on the Titin: Muscle imaging as a diagnostic marker of biallelic TTN-related myopathy
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Updated: May 27, 2025
Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease
Published on: December 18, 2016
L H Hayes1,2,3, S B Neuhaus1, S Donkervoort1
1Neuromuscular and Neurogenetic Disorders of Childhood Section, NINDS, National Institutes of Health, Bethesda, MD, USA.
Background:
The accurate diagnosis of titin-related myopathies (TTN-RM) is challenging due to the "gigantism" of the coding gene TTN with an incompletely understood landscape of normal genetic variation, an increasing number of pathogenic variants, and wide phenotypic variability of both cardiac and muscle involvement. Particularly in situations of potentially incomplete genotypes, clinicians need more phenotyping tools to help confidently determine the pathogenicity of variants in TTN and accurately diagnose titinopathies.
Objective:
To illustrate the pattern of muscle involvement found by muscle imaging in patients with TTN-RM.
Methods:
We reviewed the clinical and imaging data of patients with TTN-RM. Cross secitonal MR images of the lower extremity muscles were scored for degree of abnormality using the Mercuri scoring system and patterns were identified with comparison across muscle groups. Ultrasound images were also reviewed and described.
Results:
Eleven patients with TTN-RM had clinical and imaging data available for review. The relatively more severe involvement of the semitendinosus muscle in the hamstring group ("semitendinosus sign") emerged as a consistent feature in patients with recessive TTN-RM despite clinical heterogeneity.
Conclusions:
Here we find that despite considerable complexity, the pattern of muscle involvement on MRI and ultrasound may aid in the confirmation of TTN-RM by establishing compatibility with the diagnosis.
