Novel cytochrome c-oxidase deficiency and mitochondrial myopathy in non-syndromic cleft lip with or without palate

Abstract

The role of mitochondria in regulating cells during the embryonic phase is crucial, yet their function in causing deformation to orbicularis oris muscle of cleft lip remains controversial. The study was performed to explore morphological abnormalities of orbicularis oris muscle and mitochondria in patients with cleft lip with or without palate. Seventeen cleft lip tissue samples were obtained from consented patients who underwent cleft lip repair. All tissue samples were processed according to the respective analyses: modified Gomori trichrome, cytochrome c-oxidase (COX), adenosine triphosphatase (ATP-ase), and transmission electron microscopy (TEM). Fiber types and the sizes of fibers and mitochondria were determined using ImageJ processing program. The pathological hallmark of mitochondrial myopathy, which was the presence of ragged red fibers, and the presence of novel COX-negative fibers were observed in cleft lip tissues. Muscle fiber type ratio for type II fibers was found to be predominant in orbicularis oris muscle of cleft lip tissues with 78.43%, while type I fibers was 21.57%. The diameters of the fibers were 6.37 µm for type I, and 6.87 µm for type II. By means of electron microscopy, minimal accumulation of mitochondria and excessive lipid droplets were noted within the myofibrils of cleft lip orbicularis oris muscle. This report on series of pathologic features of the orbicularis oris muscle and mitochondria provides insights into the possibility of impaired mitochondrial function in non-syndromic cleft lip.