We identified a Japanese family with
congenital fibrosis of the extraocular muscles, including 24 affected individuals through five generations. To determine their form of
congenital fibrosis of the extraocular muscles, we performed clinical and linkage studies. DNA typing for linkage to the
FEOM1 (12p11.2-q12) and FEOM3 (16qter) loci was performed on genomic
DNA, using fluorescent microsatellite polymorphic markers. All affected individuals shared the common manifestations of
congenital fibrosis of the extraocular muscles type 1 including congenital ptosis, infraducted globe position in primary gaze, and upward gaze
palsy in both eyes. Unexpectedly, we found apparent spinal canal
stenosis in the cervical spine in all affected family members who were examined. Genetic analysis revealed linkage to the
FEOM1 locus with a maximum lod score of 4.42 at theta of zero. One affected family member harbored a recombination event between D12S345 and D12S1692, narrowing the
FEOM1 locus from the published 3-cM region flanked by D12S1584 and D12S1668 to a 2.1-cM region flanked by D12S345 and D12S1668. Thus, we have established that this family segregates
congenital fibrosis of the extraocular muscles type 1 as an autosomal dominant trait and that their disorder both maps to and refines the
FEOM1 locus. This is the first clinical and genetic report of such a family in the Japanese population and the first report of spinal involvement in
congenital fibrosis of the extraocular muscles.