Abstract
BackgroundPathogenic variants in ryanodine receptor 1 (RYR1, MIM# 180901) are the cause of congenital myopathy with fiber‐type disproportion, malignant hyperthermia susceptibility type 1, central core disease of muscle, multiminicore disease and other congenital myopathies.MethodsWe present a patient with global developmental delay, hypotonia, myopathy, joint hypermobility, and multiple other systemic complaints that were noted early in life. Later she was found to have multiple bone deformities involving her spine, with severe scoliosis that was corrected surgically. She was also diagnosed with ophthalmoplegia, chronic hypercapnic respiratory failure, and hypertension. At 22 years of age she presented to the genetics clinic with a diagnosis of mitochondrial myopathy and underwent whole exome sequencing (WES).ResultsWhole exome sequencing revealed two novel compound heterozygous variants in RYR1 (c.7060_7062del, p.Val2354del and c.4485_4500del, p.Tyr1495X).ConclusionReview of her clinical, pathologic, and genetic findings pointed to a diagnosis of a congenital myopathy with fiber‐type disproportion.
Highlights
The congenital myopathies and muscular dystrophies are clinically and genetically heterogeneous disorders (Bo€nnemann et al 2014)
Whole exome sequencing revealed two novel compound heterozygous variants in RYR1 (c.7060_7062del, p.Val2354del and c.4485_4500del, p.Tyr1495X). Review of her clinical, pathologic, and genetic findings pointed to a diagnosis of a congenital myopathy with fiber-type disproportion
We describe a patient who was diagnosed with a mitochondrial myopathy early in life
Summary
The congenital myopathies and muscular dystrophies are clinically and genetically heterogeneous disorders (Bo€nnemann et al 2014). Because of the overlap in disease phenotype across many of these disorders, marked variability in clinical presentation, and varying modes of inheritance, determining the genetic diagnosis has become increasingly challenging, even with the advent of generation sequencing in clinical practice (Bo€nnemann et al 2014). Pathogenic variants in the ryanodine receptor 1 (RYR1, MIM# 180901) gene have been implicated in a number of a 2017 The Authors. Exome Sequencing Reveals Two Novel RYR1 Variants different disorders including congenital myopathy with fiber-type disproportion (CFTD, MIM# 255310). Pathogenic variants in ryanodine receptor 1 (RYR1, MIM# 180901) are the cause of congenital myopathy with fiber-type disproportion, malignant hyperthermia susceptibility type 1, central core disease of muscle, multiminicore disease and other congenital myopathies
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