An Investigation of the Inheritance of Esotropia and Hyperopia

Abstract

Purpose: : Both strabismus and refractive error are common eye complaints and hyperopia is frequently associated with esotropia. To date little is known about the inheritance of comitant strabismus or hyperopia and the relationship between the two is uncertain. To determine whether esotropia and hyperopia are associated traits or are inherited in isolation, we ascertained, sampled and genotyped large families with esotropia.

Methods: : Twelve families with primary nonsyndromic comitant esotropia [PNCE] were recruited within the UK Hospital Eye Service. All consenting persons were clinically assessed and a whole genome linkage screen of all DNA samples was undertaken by the Marshfield Mammalian Genotyping service. Linkage between PNCE and microsatellite markers was assessed under recessive and dominant models with the program SIMWALK2. Refractive error was analysed as a quantitative trait with the program SOLAR.

Results: : Genotypes of 402 microsatellite markers were analysed for 155 DNA samples. In the analysis of PNCE as a dichotomous trait three families had LOD scores over 2, spread over six chromosomes. One peak replicated linkage to the published STBMS1 locus on chromosome 7p while the remainder pointed to potential new strabismus loci on chromosomes 1, 4, 6, 8 and 9. In the SOLAR analysis of the mean refractive error, there was just one LOD score over 2 (2.58) at marker D1S534; this decreased to 2.2 upon the addition of further markers. Multipoint linkage analysis of esotropia with refractive error as a covariate did not reveal any locus with a LOD score > 0.5.

Conclusions: : One family confirmed linkage to STBMS1; the remaining results are still undergoing investigation. Our results demonstrate that esotropia and hyperopia are inherited in a complex manner and that although hyperopia is considered a risk factor for esotropia, we cannot demonstrate any single locus of large effect either with the two traits independently or with refractive error as a covariate of esotropia.

Keywords: genetics • strabismus • refraction