TNNT1-associated nemaline myopathy: a rare case report from a tertiary centre in central India

Mukesh Bhavanagare; Shilpa Pallithrikkovil Vishnu; Shubham Kamble; Anuragsingh Chandel; Varsha Chauhan

doi:10.18203/2349-3291.ijcp20252969

Authors

Mukesh Bhavanagare Department of Pediatrics, MGIMS, Sevagram, Maharashtra, India https://orcid.org/0009-0004-6449-000X
Shilpa Pallithrikkovil Vishnu Department of Pediatrics, MGIMS, Sevagram, Maharashtra, India https://orcid.org/0009-0007-5220-3175
Shubham Kamble Department of Pediatrics, MGIMS, Sevagram, Maharashtra, India https://orcid.org/0000-0003-3812-6760
Anuragsingh Chandel Department of Pediatrics, MGIMS, Sevagram, Maharashtra, India https://orcid.org/0000-0001-5839-0249
Varsha Chauhan Department of Pediatrics, MGIMS, Sevagram, Maharashtra, India https://orcid.org/0000-0002-3907-1047

DOI:

https://doi.org/10.18203/2349-3291.ijcp20252969

Keywords:

Consanguinity, Genetic analysis, Muscle weakness, Nemaline myopathy, TNNT1 protein

Abstract

Nemaline myopathy (NM) is a rare congenital skeletal muscle disorder characterized by generalized muscle weakness and the presence of rod-like nemaline bodies within muscle fibers. Severity varies from neonatal hypotonia and respiratory failure to milder forms with delayed motor milestones. Inheritance is autosomal dominant or recessive, with mutations commonly in ACTA1, NEB, TPM3 and TNNT1. We report a case of a 3-year-old female with global motor delay, feeding difficulties and hypotonia. Whole exome sequencing revealed a homozygous TNNT1 variant (c.33-2A>T), confirming NM. Supportive care, including nutritional and physiotherapy intervention, led to clinical improvement. This report emphasizes the importance of early clinical suspicion and genetic evaluation in NM, particularly in consanguineous populations.

Metrics

Metrics Loading ...

References

Putkowski S. The National Organization for Rare Disorders (NORD) providing advocacy for people with rare disorders. NASN school nurse. 2010;25(1):38-41. DOI: https://doi.org/10.1177/1942602X09352796

North KN, Wang CH, Clarke N, Jungbluth H, Vainzof M, Dowling JJ, et al. Approach to the diagnosis of congenital myopathies. Neuromuscul Disord. 2014;24(2):97–116. DOI: https://doi.org/10.1016/j.nmd.2013.11.003

Ravenscroft G, Bryson-Richardson RJ, Nowak KJ, Laing NG. Recent advances in understanding congenital myopathies. F1000Res. 2018;7:1921. DOI: https://doi.org/10.12688/f1000research.16422.1

Johnston JJ, Kelley RI, Crawford TO, Morton DH, Agarwala R, Koch T, et al. A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. Am J Hum Genet. 2000;67(4):814–21. DOI: https://doi.org/10.1086/303089

Marra JD, Arámburu JA, Presmanes JC. A novel TNNT1 mutation causing fatal nemaline myopathy in a non-Amish patient. Neuromus Disord. 2015;25(10):771–4.

Sambuughin N, Yau KS, Olivé M, Duff RM, Sowden JE, Gonzales V, et al. Dominant mutations in TNNT1 associated with a nemaline myopathy with core-rod features. Hum Pathol. 2015;46(4):519–26.

Romero NB, Sandaradura SA, Clarke NF. Recent advances in nemaline myopathy. Curr Opin Neurol. 2013;26(5):519–26. DOI: https://doi.org/10.1097/WCO.0b013e328364d681

Boycott KM, Vanstone MR, Bulman DE, MacKenzie AE. Rare-disease genetics in the era of next-generation sequencing: discovery to translation. Nat Rev Genet. 2013;14(10):681–91. DOI: https://doi.org/10.1038/nrg3555

Monies D, Abouelhoda M, Assoum M, Al-Tassan N, Al-Hindi H, Alkuraya FS. Lessons learned from large-scale exome sequencing in Saudi Arabia. Hum Genet. 2019;138(2):151–60.

Sarkozy A, Munot P, Manzur AY, Sewry CA, Quinlivan R, Robb SA, et al. Skeletal muscle histology in 50 patients with congenital myopathy. Neuromuscul Disord. 2013;23(8):653–9.