Congenital fibrosis of the extraocular muscles type 2, an inherited exotropic strabismus fixus, maps to distal 11q13.
The extraocular fibrosis syndromes are congenital ocular-motility disorders that arise from dysfunction of the oculomotor, trochlear, and abducens nerves and/or the muscles that they innervate. Each is marked by a specific form of restrictive paralytic ophthalmoplegia with or without ptosis. Individuals with the classic form of congenital fibrosis of the extraocular muscles (CFEOM1) are born with bilateral ptosis and a restrictive infraductive external ophthalmoplegia. We previously demonstrated that CFEOM1 is caused by an autosomal dominant locus on chromosome 12 and results from a developmental absence of the superior division of the oculomotor nerve. We now have mapped a variant of CFEOM, exotropic strabismus fixus ("CFEOM2"). Affected individuals are born with bilateral ptosis and restrictive ophthalmoplegia with the globes "frozen" in extreme abduction. This autosomal recessive disorder is present in members of three consanguineous Saudi Arabian families. Genetic analysis of 70 individuals (20 affected individuals) reveals linkage to markers on chromosome 11q13, with a combined LOD score of 12.3 at the single nonrecombinant marker, D11S1314. The 2.5-cM CFEOM2 critical region is flanked by D11S4196/D11S4162 and D11S4184/1369. Two of the three families share a common disease-associated haplotype, suggesting a founder effect for CFEOM2. We hypothesize that CFEOM2 results from an analogous developmental defect to CFEOM1, one that affects both the superior and inferior divisions of the oculomotor nerve and their corresponding alpha motoneurons and extraocular muscles.
Division of Genetics, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
S M
SM
Wang
J
J
Zwaan
P B
PB
Mullaney
M H
MH
Jabak
A
A
Al-Awad
A H
AH
Beggs
E C
EC
Engle
D001763:Blepharoptosis / Q000235:genetics; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D004247:DNA / Q000097:blood; D005099:Exotropia / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D005260:Female; D005355:Fibrosis; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D008126:Lod Score; D008214:Lymphocytes; D008297:Male; D009801:Oculomotor Muscles / Q000473:pathology*; D009886:Ophthalmoplegia / Q000235:genetics; D010375:Pedigree; D013577:Syndrome
D005819:Genetic Markers; D004247:DNA