A novel KIF21A mutation in a patient with congenital fibrosis of the extraocular muscles and Marcus Gunn jaw-winking phenomenon.

OBJECTIVE: To determine whether congenital fibrosis of the extraocular muscles (CFEOM) with Marcus Gunn jaw-winking phenomenon (MG) can result from mutations in the KIF21A gene encoding a kinesin motor protein.
METHODS: An individual with CFEOM1 (classic autosomal dominant CFEOM) and MG underwent a comprehensive ophthalmic examination. He and his healthy parents underwent screening for mutations in the KIF21A gene by direct DNA sequencing. The clinical records of our previously described patients with CFEOM and KIF21A mutations were reviewed for evidence of more extensive dysinnervation.
RESULTS: A de novo and novel KIF21A mutation 2840T-->C (M947T) was present in the proband. In addition, among our previously described patients with CFEOM and KIF21A mutations, 3 individuals had MG and 1 had hypertropia during toothbrushing.
CONCLUSIONS: This report introduces a new CFEOM1 KIF21A mutation and is, to our knowledge, the first report of a genetic defect associated with MG. The combination of CFEOM1 with MG supports a primary neurogenic etiology of CFEOM resulting from KIF21A mutations. CLINICAL RELEVANCE: These findings will increase understanding of the etiology of CFEOM and increase awareness of the affiliation of CFEOM with MG.