Congenital Fibrosis of Extraocular Muscles Type 1 with Progression of Ophthalmoplegia

Recently, different syndromes with congenital, non-progressive, sporadic or familial developmental abnormalities of the cranial nerves and their nuclei were classified as congenital cranial dysinnervation syndromes (CCDD). Duane and Möbius syndromes are well-known examples of CCDD. Another syndrome is the congenital fibrosis of extraocular muscles (CFEOM), which is characterized by a mainly bilateral ophthalmoplegia of the oculomotoric and trochlearic nerves. We present the case of a 60-year-old patient with CFEOM type 1 with autosomal-dominant inheritance and typical phenotype due to the common C2860T mutation in exon 21 of the newly identified KIF21A gene on chromosome 12 encoding a kinesin motor protein responsible for axonal transport. The documented course of our patient, however, clearly showed progression of the bilateral external ophthalmoplegia over the last 23 years. At the age of 37 years he complained about newly occurring blurred vision and diplopia, which implies the capability of binocular vision before. The angle of divergence progressed from 26° at age 37 to 45° at age 50. The poor residual movement on attempted adduction and upgaze had completely disappeared at age 57. Progression of external ophthalmoplegia might be caused by either the consequence of an overuse of the reduced number of oculomotoric brain stem alpha-motoneurons or a continuous disease progression due to the kinesin defect. The present case demonstrates the possibility of progression in CFEOM1 and casts doubt on the definition of CFEOM as a strictly non-progressive disorder.