Marked neuropsychiatric involvement and dysmorphic features in nemaline myopathy

Background Inherited nemaline myopathy is one of the most common congenital myopathies. This genetically heterogeneous disease is defined by the presence of nemaline bodies in muscle biopsy. The phenotypic spectrum is wide and cognitive involvement has been reported, although not extensively evaluated. Methods We report two nemaline myopathy patients presenting pronounced central nervous system involvement leading to functional compromise and novel facial and skeletal dysmorphic findings, possibly expanding the disease phenotype. Results One patient had two likely pathogenic NEB variants, c.2943G > A and c.8889 + 1G > A, and presented cognitive impairment and dysmorphic features, and the other had one pathogenic variant in ACTA1, c.169G > C (p.Gly57Arg), presenting autism spectrum disorder and corpus callosum atrophy. Both patients had severe cognitive involvement despite milder motor dysfunction. Conclusion We raise the need for further studies regarding the role of thin filament proteins in the central nervous system and for a systematic cognitive assessment of congenital myopathy patients.