Diagnostic Reappraisal after 12-Year Follow-up of Pediatric Myopathy with Heterozygous NEB Variants and Dystrophy-Like Progression

CASE REPORT
Afërdita Tako, Mirela Tabaku, Aida Bushati, Rovena Aliaj, Armand Shehu, Sindi Dizdari, Paskal Cullufi

 

For citation: Tako A, Tabaku M, Bushati A, Aliaj R, Shehu A, Dizdari S, Cullufi P. Diagnostic Reappraisal after 12-Year Follow-up of Pediatric Myopathy with Heterozygous NEB Variants and Dystrophy-Like Progression. International Journal of Biomedicine. 2026;16(3):401-405. doi:10.21103/Article16(3)_CR4

Originally published September 5, 2026

Abstract: 

Background: Mutations in the NEB gene are the most frequent genetic cause of autosomal recessive nemaline myopathy, a clinically heterogeneous congenital myopathy.
In pediatric myopathy, longitudinal observation is essential because the evolving phenotype may challenge an initially plausible molecular interpretation and reveal features requiring diagnostic reappraisal.
Case presentation: This report describes a 12-year clinical-genetic trajectory in a child with congenital-onset myopathy, persistent hyperCKemia, two heterozygous NEB variants, and later dystrophy-like progression.  Clinical exome sequencing performed at 5 years of age identified two heterozygous NEB variants: the canonical splice-site variant c.10872+1G>C and the missense variant c.11333T>C (p.Ile3778Thr). The patient achieved independent ambulation at 20 months but later developed progressive weakness, Gowers’ sign, scapular winging, distal muscle wasting, and progressive functional decline, ultimately losing independent ambulation at 12 years. Cardiac and respiratory assessments remained normal during follow-up.
Conclusions: This report describes a 12-year clinical-genetic trajectory in a child with congenital-onset myopathy, persistent hyperCKemia, two heterozygous NEB variants of unresolved phase, and later dystrophy-like progression. The longitudinal course highlights the importance of cautious interpretation of exome findings and supports ongoing diagnostic reappraisal when evolving features broaden the neuromuscular differential diagnosis.

Keywords: 
NEB • nemaline myopathy • pediatric myopathy • hyperCKemia • longitudinal follow-up • diagnostic reappraisal
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Received May 20, 2026.
Accepted July 11, 2026.
© 2026 The Author(s). International Journal of Biomedicine is published by IMRDC. This is an open access article under the CC BY-NC-ND 4.0 license.