EC Paediatrics

Introduction: Nemaline myopathy (NM) is among the most common congenital myopathies, typically presenting with non-progressive or slowly progressive generalized muscle weakness. Histologically, NM is characterized by the presence of nemaline bodies-rod-shaped, Z-line-derived structures within skeletal muscle fibers. To date, mutations in at least twelve genes have been implicated in NM, underscoring its considerable molecular heterogeneity. Among these, mutations in NEB and ACTA1 are most frequently identified. 

Case Report: We report the case of a 56-day-old female neonate who presented with poor activity and tone at birth, with generalized hypotonia, weak reflexes, a feeble cry, and flexion contractures of both upper limbs. Pooling of secretions suggested possible bulbar involvement. Based on these neurological findings, a neuromuscular disorder was suspected. Whole-exome sequencing (WES) identified a heterozygous, likely pathogenic variant in the NEB gene, consistent with Nemaline Myopathy Type 2 (NEM2), a recessive neuromuscular condition associated with NEB mutations.

Discussion: Nemaline myopathy represents a clinically and genetically heterogeneous group of disorders that can present in the neonatal period with profound hypotonia, respiratory weakness, and feeding difficulties. Muscle biopsy and genetic testing remain key diagnostic tools. Identification of NEB gene variants through WES has significantly improved the ability to confirm the diagnosis and guide family counseling. Although there is currently no definitive cure, early diagnosis allows for timely initiation of supportive care, including respiratory assistance, nutritional management, and physiotherapy.

Conclusion: This case emphasizes the importance of early recognition of clinical signs suggestive of congenital myopathies. Prompt genetic testing facilitates accurate diagnosis, prognosis estimation, and appropriate multidisciplinary management, ultimately improving patient outcomes and aiding family planning through genetic counseling.

 Keywords: Nemaline Myopathy (NM); NEB Gene Mutation; Whole-Exome Sequencing (WES); Nemaline Myopathy Type 2 (NEM2)

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