Elsevier

Neuromuscular Disorders

Volume 14, Issue 12, December 2004, Pages 785-790
Neuromuscular Disorders

Magnetic resonance imaging of muscle in congenital myopathies associated with RYR1 mutations

https://doi.org/10.1016/j.nmd.2004.08.006Get rights and content

Abstract

Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are associated with a wide range of phenotypes, comprising central core disease and distinct subgroups of multi-minicore disease. We report muscle MRI findings of 11 patients from eight families with RYR1 mutations (n=9) or confirmed linkage to the RYR1 locus (n=2). Patients had clinical features of a congenital myopathy with a wide variety of associated histopathological changes. Muscle MR images showed a consistent pattern characterized by (a) within the thigh: selective involvement of vasti, sartorius, adductor magnus and relative sparing of rectus, gracilis and adductor longus; (b) within the lower leg: selective involvement of soleus, gastrocnemii and peroneal group and relative sparing of the tibialis anterior. Our findings indicate that patients with RYR1-related congenital myopathies have a recognizable pattern of muscle involvement irrespective of the variability of associated histopathological findings. Muscle MRI may supplement clinical assessment and aid selection of genetic tests particularly in patients with non-diagnostic or equivocal histopathological features.

Introduction

Muscle magnetic resonance imaging (MRI) is a valuable tool for the study of healthy [1] and diseased muscle and has been systematically used in the assessment of the inflammatory myopathies [2] and the muscular dystrophies [3]. More recently, we could demonstrate consistent and distinct patterns of selective muscle involvement in autosomal-dominant Emery-Dreifuss muscular dystrophy due to lamin A/C gene mutations (LGMD1B) [4], congenital muscular dystrophy with early rigidity of the spine (RSMD1) due to recessive mutations in the selenoprotein N (SEPN1) gene [5], and autosomal-dominant Bethlem myopathy secondary to mutations in the COL6A1 gene [6].

The congenital myopathies are characterized by distinct histopathological changes on muscle biopsy and have now been attributed to a variety of genetic defects predominantly affecting sarcolemmal and sarcotubular proteins. Dominant and recessive mutations in the skeletal muscle ryanodine receptor (RYR1) gene are associated with a wide range of phenotypes comprising central core disease (CCD) [7], CCD with additional nemaline rods [8], clinically distinct subgroups of minicore myopathy (Multi-minicore Disease, MmD) [9], [10] and the malignant hyperthermia susceptibility trait without abnormalities on muscle biopsy [7]. Some of the histopathological abnormalities associated with RYR1 involvement may be caused by mutations in a number of different genes, confronting the clinician with the difficult task of choosing the appropriate confirmatory genetic test in patients with a rare disorder. Muscle MRI has been suggested as a useful ancillary tool to further inform this choice in some forms of the muscular dystrophies [11], but systematic MRI studies correlating genetic and imaging data in the congenital myopathies are currently not available.

The aim of the following study was to identify patterns of selective muscle involvement in patients with mutations in the skeletal muscle ryanodine receptor (RYR1) gene and clinical and histopathological features of a congenital myopathy.

Section snippets

Patients

During the period from July 1998 to October 2002, 11 patients from eight families (F1–F8) attending the Neuromuscular Unit at the Hammersmith Hospital in London were invited to take part in our study. Five patients were female and six patients were male. Mean age at the time of the muscle MRI scan was 16 years (median 13 years; range 4–39 years).

All 11 patients had a consistent clinical phenotype with proximal weakness predominantly affecting the hip girdle, only mild facial weakness, absence

Muscle magnetic resonance imaging

All 11 patients had both thighs and lower leg muscles scanned. There was a consistent and recognizable pattern of selective muscle involvement with variations in signal intensity according to clinical severity. The typical pattern of selective involvement is shown in Fig. 2.

Discussion

Systematic muscle MRI data have not previously been reported in congenital myopathies associated with mutations in the RYR1 gene. Differential involvement of the quadriceps with relative sparing of the rectus femoris was already suggested in early ultrasound studies of CCD [16]. In a combined ultrasound and CT study of two cases from an autosomal-dominant CCD pedigree, Arai and co‐workers [17] described markedly decreased attenuation values within the soleus but relative sparing of rectus

Acknowledgements

The continuous support of the Muscular Dystrophy Campaign to the Hammersmith Hospital Neuromuscular Centre is gratefully acknowledged.

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