CFEOM1, the classic familial form of congenital fibrosis of the extraocular muscles, is genetically heterogeneous but does not result from mutations in ARIX

BACKGROUND: To learn about the molecular etiology of strabismus, we are studying the genetic basis of 'congenital fibrosis of the extraocular muscles' (CFEOM). These syndromes are characterized by congenital restrictive ophthalmoplegia affecting muscles in the oculomotor and trochlear nerve distribution. Individuals with the classic form of CFEOM are born with bilateral ptosis and infraducted globes. When all affected members of a family have classic CFEOM, we classify the family as a CFEOM1 pedigree. We have previously determined that a CFEOM1 gene maps to the FEOM1 locus on chromosome 12cen. We now identify additional pedigrees with CFEOM1 to determine if the disorder is genetically heterogeneous and, if so, if any affected members of CFEOM1 pedigrees or sporadic cases of classic CFEOM harbor mutations in ARIX, the CFEOM2 disease gene. RESULTS: Eleven new CFEOM1 pedigrees were identified. All demonstrated autosomal dominant inheritance, and nine were consistent with linkage to FEOM1. Two small CFEOM1 families were not linked to FEOM1, and both were consistent with linkage to FEOM3. We screened two CFEOM1 families consistent with linkage to FEOM2 and 5 sporadic individuals with classic CFEOM and did not detect ARIX mutations. CONCLUSIONS: The phenotype of two small CFEOM1 families does not map to FEOM1, establishing genetic heterogeneity for this disorder. These two families may harbor mutations in the FEOM3 gene, as their phenotype is consistent with linkage to this locus. Thus far, we have not identified ARIX mutations in any affected members of CFEOM1 pedigrees or in any sporadic cases of classic CFEOM

Clinical characteristics of cyclodeviation

PURPOSE: To retrospectively evaluate the incidence of cyclodeviation among patients with diplopia and analyse the causative diseases and clinical manifestations of cyclodeviation. METHODS: The medical records of 266 consecutive patients of 15 years of age or older presenting with diplopia, who had undergone the Lancaster red-green test (LRGT) from January 2001 to December 2002, were retrospectively reviewed. The presence of cyclodeviation on LRGT, predisposing conditions, causative diseases, and clinical manifestations of cyclotropia were analysed. Cyclodeviation on the LRGT were compared with those from the Maddox double-rod test (MDRT) and fundus photography. RESULTS: A total of 63 (24%) out of 266 patients exhibited cyclodeviation on LRGT. Eight out of 63 patients with cyclodeviation on the LRGT complained of torsional diplopia. Superior oblique palsy (SOP) was the most common causative disease (42 patients), followed by skew deviation (six) and thyroid orbitopathy (three). Excyclodeviation was found in 57 patients and incyclodeviation in four patients on the LRGT. The spontaneous recovery rate was 83% in patients of vascular origin and 17% of traumatic origin. Cyclodeviation with the MDRT and fundus photography showed good correlation with those obtained from the LRGT. There was no association of the amount of cyclotropia with the presence of torsional diplopia as well as with its recovery. CONCLUSION: In spite of the rare complaint of torsional diplopia, 24% of the patients with diplopia showed cyclodeviation on the LRGT. SOP was the most common causative disease. Most of the patients with cyclodeviation of a vascular origin showed spontaneous improvement

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1), additional CFEOM1 families, and a reduction of the critical region on chromosome 12.

Poster presentation at the 2000 Meeting of AAPOS in San Diego, C