Purpose: To describe phenotyping and linkage analysis results for available members from a consanguineous nuclear family with hereditary congenital strabismus.
Methods: Both parents and all 12 children underwent clinical examination. Available affected and several unaffected family members had venous blood sampling for DNA extraction and 10K single nucleotide polymorphism (SNP) genotyping (Affymetrix Gene Chip® Human). Multipoint logarithm of the odds (LOD) score calculations were performed assuming an autosomal recessive mode of inheritance with 100% penetrance and disease allele frequency of 0.01%.
Results: Three children had non-syndromic large-angle infantile esotropia without significant hyperopia. A fourth child had left esotropic Duane retraction syndrome. A fifth child who had esotropia in the setting of prematurity and childhood poliomyelitis was excluded from the analysis. A sixth child had keratoconus and was excluded. Both parents and the remaining 6 children had no significant orthoptic or ophthalmic findings. Using linkage analysis including the 4 esotropic children, disease loci were mapped to regions on chromosomes 3p26.3-26.2 and 6q24.2-25.1 using multipoint linkage analysis with LOD scores of 3.18 and 3.25 respectively. Linkage to these regions persisted when the esotropic Duane retraction syndrome patient was excluded from the linkage analysis (LOD scores of 2.00 and 2.32, respectively).
Conclusions: Non-syndromic infantile esotropia could be related to susceptibility loci on chromosomal regions 3p26.3-26.2 and 6q24.2-25.1 and may share alleles that underlie Duane retraction syndrome.