P.1.21 Congenital muscular dystrophy phenotype with excess of neuromuscular spindles in a 5-year old girl

Abstract

We report on a 5-year-old girl who presents with an association between a congenital muscular dystrophy, and very peculiar abnormalities on muscle biopsy. The girl was the second child from healthy non related Algerian parents and has now a healthy younger brother. Family history was not informative. Weak fetal movements and polyhydramnios were noticed during the pregnancy. At birth, the child presented with moderate hypotonia, pectus excavatum, mild dysmorphia, club foot, adducted thumbs and generalized proximal arthrogryposis. The girl showed normal intelligence. She had acquired a sitting position, but no ambulation or standing position. She presented with severe shoulder, hip and knee contractures contrasting with distal hyperlaxity. In addition, there was severe cyphosis and a mild scoliosis. Weakness was axial, proximal and distal, facial musculature being mostly spared. A mild right strabismus was noted. The child also presents with mitral valve dysplasia with insufficiency that required surgical correction. There was no need for ventilatory support. Whole Body Muscular MRI demonstrated a diffuse hypotrophy of muscles without selective pattern of involvement. No abnormalities suggestive of collagen VI-related myopathy or other known myopathies were identified. Immunolabelling of collagen VI in cultured fibroblasts demonstrated the absence of secretion and intracytoplasmic retention, but no mutation was detected in the COL6A1-3 genes. Muscle biopsy especially showed a dense conjunctive tissue harboring numerous ovoid formations corresponding to the neuromuscular spindle. There were only few “extrafusal” muscle fibres. No necrotic regenerative fibers were observed. To our knowledge, this pathological aspect on the biopsy has only been described in patients with HRAS mutations (test ongoing), but in contrast with the previously reported cases, the child does not present organomegaly or hypertrophic cardiomegaly and is still living at five years of age.