1. RYR1 causing distal myopathy
- Author
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Ruple S. Laughlin, Zhiyv Niu, Margherita Milone, and Eric D. Wieben
- Subjects
Adult ,Male ,0301 basic medicine ,Heterozygote ,Pathology ,medicine.medical_specialty ,Weakness ,DNA Mutational Analysis ,distal myopathy ,Polymorphism, Single Nucleotide ,Clinical Reports ,Upper Extremity ,03 medical and health sciences ,0302 clinical medicine ,Jaw Abnormalities ,Exome Sequencing ,RYR1 ,Genetics ,medicine ,Humans ,Centronuclear ,Centronuclear myopathy ,Muscle, Skeletal ,Myopathy ,Creatine Kinase ,Molecular Biology ,Genetics (clinical) ,Muscle contracture ,Clinical Report ,Muscle biopsy ,medicine.diagnostic_test ,Electromyography ,business.industry ,Ryanodine Receptor Calcium Release Channel ,Anatomy ,musculoskeletal system ,medicine.disease ,Pedigree ,Distal Myopathies ,Phenotype ,030104 developmental biology ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Central core disease ,myopathy - Abstract
Background Congenital myopathies due to ryanodine receptor (RYR1) mutations are increasingly identified and correlate with a wide range of phenotypes, most commonly that of malignant hyperthermia susceptibility and central cores on muscle biopsy with rare reports of distal muscle weakness, but in the setting of early onset global weakness. Methods We report a case of a patient presenting with childhood onset hand stiffness and adult onset progressive hand weakness and jaw contractures discovered to have two variants in the RYR1 gene. Results The patient manifested with distal upper limb weakness which progressed to involve the distal lower limb, proximal upper limb, as well as the face in addition to limited jaw opening. Creatine kinase was mildly elevated with EMG findings supporting a myopathy. Muscle biopsy showed features consistent with centronuclear myopathy. Whole exome sequencing revealed a novel heterozygous pathogenic variant in RYR1 (c.12315_12328delAGAAATCCAGTTCC, p.Glu4106Alafs*8), and a heterozygous missense variant (c.10648C>T, p.Arg3550Trp) of unknown significance in compound heterozygous state. Conclusion We expand the spectrum of RYR1-related myopathy with the description of a novel phenotype in an adult patient presenting with hand weakness and suggest considering RYR1 analysis in the diagnosis of distal myopathies.
- Published
- 2017