Key result
A homozygous TNNC2 splice variant caused a recessive form of severe neonatal hypotonia in 2 siblings, resulting in 1 neonatal death and 1 medical termination of pregnancy.
Why the study?
TNNC2-related congenital myopathies had previously only been linked to autosomal dominant missense variants.
Case Report (n=2)
This is the first report of a recessive form of severe neonatal hypotonia due to a TNNC2 variant, expanding the known spectrum of TNNC2-related myopathies.
Expands TNNC2 testing to recessive variants in congenital myopathy; extends dominant-only paradigm but remains hypothesis-generating.
The TNNC2 gene is crucial for skeletal muscle function, and pathogenic variants have been linked to congenital myopathies characterized by hypotonia, muscle weakness, and respiratory insufficiency. To date, TNNC2 -related myopathies have been associated only with autosomal dominant missense variants. We report here the first family case of a recessive form of myopathy related to TNNC2 . We identified the homozygous splice variant TNNC2 (NM_003279.3):c.314 + 1G > C p.(?) in two siblings with a severe clinical presentation, resulting in one neonatal death and one medical termination of pregnancy. This variant induces a splicing defect that leads to a complete loss of the TNNC2 physiological transcript . This case expands the spectrum of TNNC2 variants with a late-onset fetal loss. To the best of our knowledge, this is the first case reporting a recessive form of severe neonatal hypotonia due to TNNC2 variant.
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Maino et al. (2025) conducted a case report in Neonatal hypotonia (n=2). Homozygous splice variant TNNC2 (NM_003279.3):c.314 + 1G > C was evaluated on Severe clinical presentation (neonatal death and medical termination of pregnancy). A homozygous TNNC2 splice variant caused a recessive form of severe neonatal hypotonia in 2 siblings, resulting in 1 neonatal death and 1 medical termination of pregnancy.
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