Left ventricular non-compaction in a hypermobile adolescent harboring a novel troponin I (TNNI3) variant (p.K106N): a case report
Abstract
Background: Left ventricular non-compaction (LVNC) is a genetically heterogeneous cardiomyopathy linked to sarcomeric and cytoskeletal genes, yet only one case has previously been associated with a troponin I (TNNI3) variant. Our case report describes the exceptionally rare coexistence of LVNC, a novel TNNI3 variant, and a hypermobile Ehlers-Danlos syndrome (hEDS) phenotype, genetically unrelated to TNNI3, resulting in a distinct clinical presentation.
Case summary: A 17-year-old female with joint hypermobility, chronic musculoskeletal pain, and a strong maternal history of Ehlers-Danlos syndrome (EDS) presented after a right shoulder subluxation. Screening echocardiogram unexpectedly revealed LVNC with mildly reduced systolic ventricular function. Cardiopulmonary exercise testing showed reduced peak VO2 and markedly elevated VE/VCO2 slope. Genetic testing identified a rare heterozygous TNNI3 variant of uncertain significance (c.318 G > C; p.K106N) within a conserved regulatory domain of cardiac troponin I, with no additional pathogenic variants in LVNC- or connective tissue-associated genes; cascade testing revealed the same variant in her mother.
Discussion: TNNI3-associated LVNC is extraordinarily rare. TNNI3 encodes cardiac troponin I, typically linked to hypertrophic and restrictive cardiomyopathy, occasionally dilated cardiomyopathy, and only rarely LVNC. LVNC has been reported in EDS almost exclusively in vascular EDS related to COL3A1, not in hEDS, adding further…
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