Early Findings in Neonatal Cases of RYR1–Related Congenital Myopathies

Figures

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  Figure 1. Histopathological and ultrastructural features on transverse sections of muscle biopsy of RYR1-RCM. Muscle biopsy from Patient I performed at 5 days of life in the first line. (A) Gomori Trichromic staining showed fiber size variability; (B) Tiny cytochrome-C oxidase deficiency at COX staining; (C) Central core and rod-core elements at electron microscopy. Muscle biopsy from Patient II was performed at 37 days of life in the second and third lines. (D) Severe type I fibers hypotrophy at Hematoxylin-Eosin, (E) Gomori trichromic, (G) NADH-TR, and (H) ATPase after acid preincubation showing predominance of darker staining hypotrophic type 1 fibers. (F,I) Electron microscopy showing focal areas of sarcomeric abnormalities with Z-line streaming and, in rare fibers, subsarcolemmal and intermyofibrillar deposits of free glycogen. Muscle biopsy from Patient III.1 was performed at 2 years of age in the fourth line. Fiber size variability with fiber I hypotrophy, fiber splittings, and moderate connective tissue increase (J) Hematoxylin-Eosin and (K) Gomori Trichromic; (L) Z-line streaming at electron microscopy.

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  Figure 2. Brain MRI. (A.I) Fetal brain MRI (Patient II; 27 G.A.), axial SShTSE T2 images showing a bilateral enlargement of periencephalic spaces. (A.II) Brain MRI coronal and axial TSE T2 image (Patient II; 2 months) showing enlargement of periencephalic spaces with subdural hematoma, multiple punctate lesions correlated with prematurity in the periventricular white matter. (B.I) Spectral brain MRI with a single voxel = 35 ms positioned at the left basal ganglia showing a slight increase of lactate peak (Patient I, 15 days). (B.II) Axial and coronal TSE T2 image showing a bilateral optic nerve thinning and the subdural hematoma (Patient I, 15 days).

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  Figure 3. Muscle MRI. (A.I) Muscle MRI (Patient II; 18-months old) axial TSE T1 images at thigh and lower leg level showing a bilateral and symmetrical atrophy and fatty infiltration of gluteus maximus, sartorius, adductor magnum and, at lower leg level, in soleus muscle a pattern compatible with RYR1-RCM. (A.II) Muscle MRI (Patient III.1; 5 years old) axial TSE T1 images at thigh and lower leg level showing a bilateral and symmetrical atrophy and fatty infiltration of vastus lateralis, sartorius, adductor magnum and, at lower leg level, in soleus muscle a pattern compatible with RYR1-RCM. (A.III) Muscle MRI (Patient III.2; 7 years old) axial TSE T1 images showing bilaterally muscle atrophy with diffuse fat substitution of pelvic girdle muscles thigh and lower leg muscles, with relative sparing of rectus femoris, adductor longus, gracilis, and tibialis anterioris.