Early Morphological Changes of the Rectus Femoris Muscle and Deep Fascia in Ullrich Congenital Muscular Dystrophy

Patrizia Sabatelli,Vittoria Cenni,Alberto Di Martino,Cesare Faldini,Luciano Merlini

doi:10.3390/ijerph19031252

Abstract

Ullrich congenital muscular dystrophy (UCMD) is a severe form of muscular dystrophy caused by the loss of function of collagen VI, a critical component of the muscle-tendon matrix. Magnetic resonance imaging of UCMD patients’ muscles shows a peculiar rim of abnormal signal at the periphery of each muscle, and a relative sparing of the internal part. The mechanism/s involved in the early fat substitution of muscle fiber at the periphery of muscles remain elusive. We studied a muscle biopsy of the rectus femoris/deep fascia (DF) of a 3-year-old UCMD patient, with a homozygous mutation in the COL6A2 gene. By immunohistochemical and ultrastructural analysis, we found a marked fatty infiltration at the interface of the muscle with the epimysium/DF and an atrophic phenotype, primarily in fast-twitch fibers, which has never been reported before. An unexpected finding was the widespread increase of interstitial cells with long cytoplasmic processes, consistent with the telocyte phenotype. Our study documents for the first time in a muscle biopsy the peculiar pattern of outside-in muscle degeneration followed by fat substitution as already shown by muscle imaging, and an increase of telocytes in the interstitium of the deep fascia, which highlights a potential involvement of this structure in the pathogenesis of UCMD.

Highlights

Collagen VI is a microfibrillar collagen expressed in the matrix of most tissues
Muscle magnetic resonance of the thigh in the Ullrich congenital muscular dystrophy (UCMD) patient at the age of 6 years showed a rim of fat tissue in the vastus lateralis and rectus femoris, as indicated by an area of high signal density closely associated to the peripheral fascia
The muscle biopsy/deep fascia (DF) of the rectus femoris matches the peculiar pattern of outside–in muscle degeneration followed by fat substitution documented by muscle imaging

Summary

Introduction

Collagen VI is a microfibrillar collagen expressed in the matrix of most tissues. The best-characterized and most widely expressed form of collagen VI is the [α1, α2, α3]heterotrimer [1]. The best-characterized and most widely expressed form of collagen VI is the [α1, α2, α3]. By interacting with cell membrane receptors and extracellular components, collagen VI fibrils form a network that connects the cell cytoskeleton to the extracellular environment [1,5]. The role of collagen VI is relevant for muscle-tendon unit function. The muscletendon unit involves the connection between the muscles and tendons, through which contractile forces are generated and transmitted [6]. The muscular/deep fascia (DF), the connective tissue sheath surrounding skeletal muscle, contributes to the transmission of muscular force between adjacent synergistic muscles [7,8]. Collagen VI localizes in the basement of muscle fibers and blood vessels and in the interstitium (epimysium, perimysium, and endomysium), Int. J.

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