Abstract
Purpose: :
Congenital fibrosis of the extraocular muscles (CFEOM) is a non-progressive disorder of ocular motility characterized by restrictive ophthalmoplegia and congenital blepharoptosis. Three types of CFEOM exist. CFEOM1 and CFEOM3 are due to mutations in KIF21A, a gene located in chromosome 12q12 and encoding a member of the kinesin family of proteins involved in the transport of essential cellular components along axonal and dendritic microtubules. Mutations in KIF21A are believed to cause alterations in axonal routing and transportation which lead to ocular motility disorders. KIF21A arginine residue at position 954 is altered in more than 80% of all individuals with KIF21A mutations reported to date. The analysis of CFEOM patients from distinct ethnic groups would help to establish the relative frequency of specific KIF21A mutations. The purpose of this study was to identify mutations in the KIF21A gene in two Mexican patients with CFEOM.
Methods: :
Two unrelated patients with CFEOM consulting at the Ophthalmology Institute "Fundación Conde de Valenciana" in Mexico-City were included. A complete ophthalmologic examination, orbital CT and analysis of the KIF21A gene by means of PCR and automated sequencing, were performed in both subjects.
Results: :
Both cases were sporadic. Patient 1 was a 19 year old girl with a best corrected visual acuity (BCVA) of 20/25 in the right eye (OD) and 20/40 in the left eye (OS). She had undergone two eye surgeries before presenting. She showed limitations in all gaze directions, particularly in supraversion, and bilateral ptosis. CT evidenced bilateral thinning of the superior muscular complexes. Patient 2 was a 9 year old girl with a BCVA of 20/70 OD and 20/40 OS. She had bilateral limitations in all gaze directions, paradoxical convergence, occlusion nystagmus, esotropia and bilateral ptosis. CT showed fibrosis of the extraocular muscles. In both patients, genetic analysis disclosed an identical c.2860C>T point mutation, predicting a change from arginine to tryptophan at residue 954 (R954W).
Conclusions: :
We report two cases of Mexican patients with CFEOM, which had an R954W mutation in KIF21A. Our results support previous findings indicating that recurrent, de novo mutations at KIF21A R954 are the most common CFEOM cause in different populations.
Keywords: genetics • strabismus • eyelid