Work

Over‐Representation of TTN Truncating Variants in a Finnish Cohort of Patients With Axial Myopathy

Year: 2026

Type: article

Abstract: BACKGROUND: Axial myopathies present with late onset selective paravertebral weakness causing bent spine/camptocormia or dropped head, and the genetic basis remains currently only partially understood. Truncating variants in TTN (TTNtv) are found in about 1% of the general population and, when biallelic, cause recessive titinopathies. Also, TTNtv located in cardiac exons are known to confer an increased risk of cardiomyopathy, with incomplete penetrance. METHODS: We retrospectively analyzed 55 Finnish adults with late-onset axial myopathy evaluated at the Tampere Neuromuscular Center (2015-2025). Clinical, imaging, and histopathological data were collected, and genetic testing was performed using the MYOcap targeted next-generation sequencing panel. RESULTS: ). The variants were ultra-rare, distributed across different exons expressed in skeletal muscle, and five were absent from gnomAD. Mean age at onset was 60 ± 11 years; six patients were female, and five reported a positive family history. Camptocormia was the main presentation, with muscle MRI showing a consistent fatty-fibrous replacement of paravertebral muscles in all cases. Muscle biopsies revealed either myopathic or myofibrillar changes without a uniform pattern. CONCLUSIONS: Heterozygous TTNtv are significantly enriched in patients with late-onset axial myopathy, suggesting a potential contribution to this phenotype. These findings broaden the clinical spectrum of titin-related diseases and support inclusion of TTN in genetic testing for idiopathic axial myopathies.

Source: European Journal of Neurology

DOI: 10.1111/ene.70537

Authors: Maria Francesca Di Feo, Giuliana Capece, Marco Savarese, Bjarne Udd, Manu Jokela, Johanna Palmio