A Novel MYH14 Variant Presenting as a New Phenotype of MYH14-Associated Neuromuscular Disorders—Clinicohistologic Findings and Review of the Literature

Abstract Background: Pathogenic variants in the nonmuscle myosin, MYH14 , have been associated with several pathologic conditions including a complex phenotype with peripheral neuropathy, myopathy, hoarseness, and hearing loss. Since its first description in a large Korean kindred, this rare neuromuscular disorder has further been characterized in 1 American and 1 Canadian pedigree. Case presentation: Here, we describe a German patient with atypical MYH14 -related neuromuscular disorder. The clinical phenotype included signs of a distal myopathy with early respiratory involvement and a prominent hoarseness and peripheral neuropathy. In contrast to previous reports, no relevant deafness was identified. Muscle biopsy indicated a vacuolated myopathy with excessive autophagy, whereas histology of the sural nerve showed signs of a mixed axonal-demyelinating neuropathy. Next-generation sequencing revealed a loss-of-function variant not identified so far in the MYH14 gene (c.4510del, p.[Arg1504Glyfs*10]). Because of rapid disease progression with respiratory failure, the patient died at the age of 52. Conclusions: We present a novel MYH14 variant resulting in a severe and rapidly progressive MYH14 -associated phenotype with predominantly distal myopathy, early respiratory failure, dysphagia, hoarseness, and peripheral neuropathy, without hearing loss. This case expands the clinical spectrum of MYH14 -related neuromuscular disorders by providing a new clinical phenotype and disease course and histopathologic features.