Histological and Molecular Manifestations of Cleft Myopathy

Objective Apart from rupture and displacement of muscle fibers, structural defects exist in cleft muscles but have not been adequately investigated. This study aimed to examine the histological and molecular features of the cleft muscles. Design Orbicularis oris (OO) and tensor fasciae latae (TFL) muscle samples were obtained from patients with cleft lip and alveolar. The non-cleft OO muscles were obtained from patients with facial trauma. Myofiber histology, stem cell composition, and molecular signatures were compared among the cleft OO muscle, non-cleft OO muscle, and TFL muscle. Main Outcome Measures Histological analysis of the fibrotic area, myofiber size, fiber type composition, and dystrophin expression pattern was performed to characterize the pathological manifestations in cleft muscles. Immunofluorescent staining of Pax7 + muscle satellite cells (MuSCs) and PDGFRα + fibro-adipogenic progenitors (FAPs) and transcriptional profiling of MuSCs were carried out to explore the stem cell number and behavior in the cleft muscle. Results Cleft muscles had an increased fibrotic area, variation in fiber size, and proportion of human fast myofiber. The defect in dystrophin expression was considerable in the non-cleft OO muscle and was even higher in the cleft OO muscle. MuSCs from cleft muscles showed a trend of increased Dux4 signature gene expression and repressed Pax7 target gene expression. Conclusion Cleft myopathy resembles facial muscle-specific muscular dystrophy. The characterization of structural deformity inherited in cleft muscles could pave the way for a deeper understanding of orofacial cleft pathology.