Last modified: 2014-04-03
Abstract
The ryanodine receptor gene (RYR1) encodes the sarcoplasmic reticulum calcium release channel RYR1. RYR1 mutations cause susceptibility to malignant hyperthermia (MH) and various congenital myopathy subtypes (congenital fiber-type disproportion, centronuclear myopathy, central core myopathy and multiminicore myopathy). Here we report clinical, pathologic and genetic features of three patients from two families with RYR1 mutations and atypical clinical and histological phenotypes. The first case is an 18-year old female patient with stable and generalized muscle weakness, atrophy and skeletal deformities since the first months of life. Her muscle biopsy showed an intense dystrophic process without specific structural defects, and the initial diagnosis was congenital muscular dystrophy. She had the homozygous mutationc.122T>C. The second and third patients are two siblings with neonatal hypotonia, motor developmental delay, proximal weakness, calf hypertrophy, normal CK, no ophthalmoplegia and muscle biopsy compatible with centronuclear myopathy. They are compound heterozygous for two RYR1 mutations: one frameshift deletion, c.6797-6_6798del, and a missense c.9892G>A. Our findings support the clinical and histological variability associated with mutations on RYR1 gene, and confirm previous studies that indicate the need to investigate RYR1 mutations in patients with congenital muscular dystrophies or centronuclear myopathies with no genetic confirmation.