A Novel Homozygous MYH2 Variant Causing Early-Onset External Ophthalmoplegia and Proximal Myopathy in a...

Mutations in the MYH2 gene, which encodes skeletal muscle myosin heavy chain IIa, are a rare cause of congenital myopathies characterized by proximal muscle weakness and ophthalmoplegia. MYH2-related disease may be inherited in either an autosomal dominant or autosomal recessive manner. Autosomal recessive MYH2-related myopathy is uncommon and may be difficult to recognize because of overlapping clinical features with neuromuscular junction disorders. We report a six-year-old boy born to consanguineous parents who presented with congenital bilateral ptosis, external ophthalmoplegia, and progressive non-fluctuating proximal muscle weakness. Neurological examination showed marked limitation of eye movements, proximal limb weakness, preserved reflexes, and normal cognitive development. Brain MRI and metabolic investigations were normal. Whole exome sequencing identified a novel homozygous MYH2 variant, c.1124A>C (p.Gln375Pro), while both parents were heterozygous carriers, consistent with autosomal recessive inheritance. The variant affects a highly conserved residue within the myosin motor domain and is absent from population databases. The clinical phenotype was consistent with previously reported cases of recessive MYH2-related myopathy. This case expands the mutational spectrum of MYH2-associated disease and highlights the importance of genetic evaluation in children presenting with congenital ophthalmoplegia and proximal muscle weakness.