Ryanodine myopathies without central cores-clinical, histopathologic, and genet...

• Autor(es): Rocha, J ; Taipa, R ; Melo Pires, M ; Oliveira, J ; Santos, R ; Santos, M
• Data: 2014
• Identificador Persistente: http://hdl.handle.net/10400.23/673
• Origem: Repositório Científico do Hospital de Braga
• Assunto(s): Criança; Canal de Libertação de Cálcio do Receptor de Rianodina; Miopatias Congénitas Estruturais
• Tipo de Documento: Artigo
• Idioma: Inglês

Descrição

BACKGROUND: Mutations in ryanodine receptor 1 gene (RYR1) are frequent causes of myopathies. They classically present with central core disease; however, clinical variability and histopathologic overlap are being increasingly recognized. PATIENTS: Patient 1 is a 15-year-old girl with mild proximal, four-limb weakness from age 5, presenting with a progressive scoliosis starting at age 10. Patient 2 is an 18-year-old girl with progressively worsening muscle hypotrophy and mild proximal, four-limb weakness. She developed a rapidly progressive scoliosis from age 11 and needed surgical treatment at age 14 years. Patient 3 is an 11-year-old boy with moderate proximal limb weakness and progressive neck flexor weakness, first noticed at age 2. Muscle biopsies revealed type 1 fiber predominance (Patients 1 and 2) or abnormal type 1 fiber uniformity (Patient 3). Different RYR1 variants were identified in all patients. In Patients 1 and 3, these changes were validated as being pathogenic. CONCLUSIONS: These patients illustrate early-onset, progressive myopathies with predominant axial involvement. Histopathologic findings were abnormal but not specific for a diagnosis, particularly central core myopathy. Genetic testing helped broaden the range of phenotypes included in the RYR1-related myopathies. Our patients reinforce the need to recognize the broad histopathologic variability of RYR1-related myopathies and sometimes lack of pathognomonic findings that may reduce the diagnostic threshold of this disease. We suggest that the predominance of type 1 fibers and involvement of axial muscles may be an important element to consider the RYR1 gene as candidate.