Neonatal nemaline myopathy associated with NEB variants and a favorable 3-year outcome: A case report

Rationale

Nemaline myopathy (NM) is a rare congenital myopathy characterized by muscle weakness and hypotonia. Severe neonatal disease may involve respiratory failure and bulbar dysfunction. Variants in the nebulin gene (NEB) are a common genetic cause, but genotype-phenotype relationships and prognosis remain variable. Patient concerns: A female neonate developed cyanosis, bradycardia, respiratory distress, and hypotonia shortly after birth. She required invasive mechanical ventilation and later experienced recurrent respiratory deterioration, difficulty weaning from ventilatory support, poor feeding, vomiting and choking, weak sucking and swallowing, and diminished primitive reflexes. Diagnoses: The clinical phenotype and trio whole-exome sequencing findings supported a clinical diagnosis of NM associated with NEB variants. Sequencing identified a maternally inherited pathogenic frameshift variant, c.23910_23911delAG (p.Arg7970SerfsTer9), and 2 missense variants classified as variants of uncertain significance: maternally inherited c.5615C>T (p.Pro1872Leu) and paternally inherited c.19550G>A (p.Arg6517His). Muscle biopsy, allelic phasing, and functional studies were unavailable; therefore, the molecular diagnosis was not definitive.