Abstract
Ryanodine receptor type 1-related congenital myopathies are the most represented subgroup among congenital myopathies (CMs), typically presenting a central core or multiminicore muscle histopathology and high clinical heterogeneity. We evaluated a cohort of patients affected with Ryanodine receptor type 1-related congenital myopathy (RYR1-RCM), focusing on four patients who showed a severe congenital phenotype and underwent a comprehensive characterization at few months of life. To date there are few reports on precocious instrumental assessment. In two out of the four patients, a muscle biopsy was performed in the first days of life (day 5 and 37, respectively) and electron microscopy was carried out in two patients detecting typical features of congenital myopathy. Two patients underwent brain MRI in the first months of life (15 days and 2 months, respectively), one also a fetal brain MRI. In three children electromyography was performed in the first week of life and neurogenic signs were excluded. Muscle MRI obtained within the first years of life showed a typical pattern of RYR1-CM. The diagnosis was confirmed through genetic analysis in three out of four cases using Next Generation Sequencing (NGS) panels. The development of a correct and rapid diagnosis is a priority and may lead to prompt medical management and helps optimize inclusion in future clinical trials.
Highlights
Ryanodine receptor type 1-related congenital myopathies (RYR1-RCM) are the most represented subgroup among congenital myopathies (CM) and are associated with mutations in RYR1 [1,2,3]
We selected four cases of severe neonatal onset RYR1-RCM focusing on the early findings, the driving diagnostic elements, and the subsequent follow-up (Table 1)
A muscle biopsy was performed in the first days of life, muscle ultrastructural studies were carried out only in two patients showing abnormalities typical of CM
Summary
Ryanodine receptor type 1-related congenital myopathies (RYR1-RCM) are the most represented subgroup among congenital myopathies (CM) and are associated with mutations in RYR1 [1,2,3]. RYR1 is a large gene encoding calcium-(Ca2+) channel (RyR1), which is a homotetrameric protein embedded in the sarcoplasmic reticulum membrane of skeletal muscle [4, 5]. Mutations in RYR1 can be extremely heterogeneous even in patients showing the same genotype [6,7,8]. RYR1-RCM manifests with symptoms ranging from perinatal onset with floppy baby syndrome to late-onset
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