Congenital fibrosis of the extraocular muscles (CFEOM) is a heterogeneous non-progressive eye movement disorder, which results from the dysfunction of all or part of the oculomotor nerve (cranial nerve III) and/or the muscles this cranial nerve innervates. CFEOM is characterized by a variable restrictive external ophthalmoplegia, ptosis and eyes that are fixed in an abnormal position. The classification of CFEOM is based on clinical manifestations and genetic classification is based on molecular analysis. To date, there are seven forms and four genetic loci for CFEOM. CFEOM1, CFEOM2, CFEOM3 and Tukel syndrome have been mapped, and mutations in KIF21A and PHOX2A have been found to cause CFEOM1 and CFEOM2, respectively.
CFEOM1 is the most common form of the condition affecting at least 1 in 230,000 people worldwide. It is inherited as an autosomal dominant pattern, characterized by bilateral ptosis, ophthalmoplegia, and hypotropic eyes with chin up position. Affected patients may require a stepwise surgical approach to correct strabismus and eyelid position.
CFEOM1 has been found to be due to mutation in the KIF21A gene, which encodes a kinesin motor protein involved in the anterograde transport of cargo along the cellular cytoskeleton of microtubules, and is likely to be essential in the normal development of cranial nerve III, which emerges from the brain and controls muscles that raise the eyes and eyelids.