Oculomotor nerve and muscle abnormalities in congenital fibrosis of the extraocular muscles

Abstract

Congenital fibrosis of the extraocular muscles is an autosomal dominant congenital disorder characterized by bilateral ptosis, restrictive external ophthalmoplegia with the eyes partially or completely fixed in an infraducted (downward) and strabismic position, and markedly limited and aberrant residual eye movements. It has been generally thought that these clinical abnormalities result from myopathic fibrosis of the extraocular muscles. We describe the intracranial and orbital pathology of 1 and the muscle pathology of 2 other affected members of a family with chromosome 12-linked congenital fibrosis of the extraocular muscles. There is an absence of the superior division of the oculomotor nerve and its corresponding alpha motor neurons, and abnormalities of the levator palpebrae superioris and rectus superior (the muscles innervated by the superior division of the oculomotor nerve). In addition, increased numbers of internal nuclei and central mitochondrial clumping are found in other extraocular muscles, suggesting that the muscle pathology extends beyond the muscles innervated by the superior division of cranial nerve III. This report presents evidence that congenital fibrosis of the extraocular muscles results from an abnormality in the development of the extraocular muscle lower motor neuron system.

Transplantation of Xenopus laevis ears reveals the ability to form afferent and efferent connections with the spinal cord

“…Such rerouting to novel targets can be induced by ablation of innervations of a given muscle fiber inducing the attraction of nearby motoneuron axons to expand to denervated targets in X. laevis Sonntag, 1990, 1991), mice (Fritzsch et al, 1995;Porter and Baker, 1997) and man (Engle et al, 1997;Miyake et al, 2008). We cannot exclude such near range attractive signaling from denervated hair cells.…”

KIF21A-Mediated Axonal Transport and Selective Endocytosis Underlie the Polarized Targeting of NCKX2

“…Mutations in KIF21A cause congenital fibrosis of extraocular muscle type I (CFEOM1), which is a disorder of the superior oculomotor nerve (Yamada et al, 2003). The prevalent hypothesis for the pathogenesis of CFEOM1 is aberrant axonal routing and resultant abnormal development of the oculomotor axis (Engle et al, 1997;Heidary et al, 2008). Given that calcium plays a crucial role in axon guidance (Gomez and Zheng, 2006), a defect in axonal transport of NCKX2 might be the direct cause of CFEOM1.…”

Human Genetic Disorders of Axon Guidance

“…The oculomotor inferior division and abducens nerves were also small (Engle et al 1997). Although the autopsy technique did not permit identification of aberrant innervation, subsequent MR imaging confirmed the autopsy findings and noted misinnervation of the lateral rectus muscle by an oculomotor nerve branch (Demer et al 2005).…”