CFEOM3: A new extraocular congenital fibrosis syndrome that maps to 16q24.2-q24.3

PURPOSE. To define the clinical characteristics and determine the gene loca lization for a previously undescribed form of congenital fibrosis of the ex traocular muscles (CFEOM), referred to as CFEOM type 3 (CFEOM3). METHODs. A large family with CFEOM was identified, and participating indivi duals underwent ophthalmologic examination and donated blood for genetic an alysis. The family's disorder was tested for linkage to the known CFEOM loc i, followed by a genome-wide search and linkage refinement using polymorphi c DNA markers. RESULTS. Thirty-eight members of this Canadian family participated in the s tudy. Affected individuals are born with a nonprogressive eye movement diso rder characterized by variable expression of ptosis and restrictive externa l ophthalmoplegia. Severely affected individuals have ptosis, primary gaze fixed in a hypo- and exotropic position, and marked restriction of eye move ment bilaterally. Mildly affected individuals have normally positioned glob es with a limitation of vertical gaze. Moderately affected individuals have asymmetrical involvement with one eye severely and one eye mildly affected . The disorder is autosomal dominant with variable expression and probable incomplete penetrance. Genetic analysis reveals linkage to markers on 16q24 .2-q24.3. A maximum lod score of 5.8 occurs at markers D16S3063 and D16S689 , and the CFEOM3 disease gene is located within a approximate to 5.6-cM reg ion flanked by D16S486 and D16S671. CONCLUSIONS. These data establish that CFEOM3 is a phenotypically variant a nd genotypically distinct form of CFEOM with linkage to chromosome 16qter. The authors have previously demonstrated that CFEOM1 results from a develop mental absence of the superior division of the oculomotor nerve. The author s hypothesize that CFEOM3 results from a defect analogous to, but distinct from, CFEOM1.