A clinically variant fibrosis syndrome in a Turkish family maps to the CFEOM1 locus on chromosome 12

Objectives: To describe the phenotype of a Turkish family with variably exp ressed congenital fibrosis of the extraocular muscles (CFEOM), and to deter mine the genetic location of their disorder. Methods: Participants were examined and had blood extracted for genetic ana lysis. The clinical features of the family's disorder were studied, and the disorder was tested for linkage to the 3 known CFEOM loci (CFEOM1, CFEOM2; and CFEOM3). Results: Twenty-nine affected and 31 unaffected family members participated in the study. Eighteen affected individuals had congenital bilateral ptosi s and restrictive infraductive (downward) ophthalmoplegia, consistent with the published descriptions of classic CFEOM families linked to the CFEOM1 l ocus. Eleven affected individuals, however, had eye(s) in a neutral primary position, residual upgaze, and/or absence of ptosis, thus deviating from p revious descriptions of CFEOM1-linked families. Analysis of the autosomal d ominant variably expressed disorder in this family revealed linkage to the CFEOM1 locus on chromosome 12 with a maximum lod score of 10.8 at D12S85. Conclusions: This Turkish Family segregates a variably expressed form of CF EOM that most closely resembles CFEOM3-linked CFEOM, but maps to the CFEOM1 locus. Clinical Relevance: These data establish that there is much greater phenoty pic heterogeneity at the CFEOM1 locus than previously reported, and this ma y blur our ability to distinguish the different CFEOM loci based solely on clinical presentation.