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Título

Histopathological findings of ryanodine receptor 1 (RYR1)-related myopathies in a cohort from a tertiary neuromuscular center.

Resumo

Introduction: Ryanodine receptor 1(RYR1)-related myopathy presents with a variety of phenotypes characterized by early onset of symptoms such as hypotonia, delayed motor development, proximal muscle weakness, ptosis and/or ophthalmoparesis, facial weakness, thoracic deformities, and spinal involvement. Among the congenital myopathies, RYR1-related myopathy is the most frequently diagnosed which includes a heterogeneous spectrum of histopathological and clinical subtypes followed by variable disease severity.

Objectives: To describe the epidemiological and histopathological findings on muscle biopsy of a case series with RYR1-related myophaties in a tertiary referral center.

Methods: We retrospectively selected patients who had a clinical history of proximal myopathy or congenital myopathy and a positive genetic test for the RYR1 gene. We evaluated clinical features and histological aspects. The evaluation of muscle biopsies included grading the fiber variability, nuclei internalization, presence of type 1 or type 2 atrophy, intermyofibrillar disorganization, presence of cores and presence of necrosis.

Results: Thirty-one patients with RYR1-related myopathy were included. Age varied from 4 to 62 years old (median age of 17). Most patients (61.3%) were male,. The most common phenotype was classical congenital myopathy (25/31), representing 80%, followed by later-onset congenital myopathy with 9.6%. One patient presented with rhabdomyolysis phenotype and one patient with a distal myopathy. Ptosis was reported by 22.5% of the patients and a history of malignant hyperthermia in one patient. Regarding histological findings, central core pattern appeared in five cases,. The centronuclear pattern occurred in six patients, as well as dystrophic pattern was seen in other six ones. Importantly, one patient showed abundant necrosis on muscle biopsy, in addition to the presence of intracytoplasmic cores.

Discussion: We present a large cohort of patients with genetically confirmed RYR1-related myopathy. Histopathological findings varied, as did phenotypes. Most patients had dystrophic or centronuclear patterns. An interesting finding was the presence of abundant fiber necrosis in one patient, which is not a characteristic usually described in these patients. The broad spectrum of RYR1-related myopathy is not only clinical but also histological.

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Doenças Neuromusculares