SCIENTIFIC REPORT Genotypic and phenotypic heterogeneity in familial microcoria

Aims: To describe the clinical features and genetic findings in two families presenting with microcoria inherited as an autosomal dominant trait. Methods: Both affected and unaffected members of two families displaying familial microcoria were examined. Flash photography or infrared pupillography were used to assess pupils, and a full ophthalmic examination including visual acuity and field testing, refraction, biomicroscopy of anterior and posterior segments, and measurement of intraocular pressure were performed. DNA from the blood of affected and unaffected family members was investigated using standard markers to look for a possible gene defect in the chromosome 13q31–q32 region. Results: All affected members of both families had pinpoint pupils which responded normally to light and accommodation. None of these subjects exhibited any other ocular abnormality. The iris of affected members showed stromal thinning and apparent absence of the iris dilator muscle in the first family, but was smooth and lacked all trabecular structure in the second family. The microcoria was present at birth in the first family but developed progressively at a later age in the second family. Haplotype analysis suggested the gene defect is not located in the chromosome 13q31–q32 region in the first family but the evidence was not conclusive in the second family. Conclusion: Although both families presented with similar pupil abnormalities inherited as an autosomal dominant trait, they show important phenotypic and genotypic differences suggesting that this is a heterogeneous condition. The possible mechanisms underlying the microcoria are discussed. F amilial microcoria is a rare disorder usually inherited as an autosomal dominant trait, although two instances of recessive inheritance have been reported. 10 The pupil abnormality usually occurs as an isolated congenital abnormality associated with failure of development, absence, or fibrosis of the dilator pupillae muscle. In some instances there is also goniodysgenesis 9 15 or a persistent pupillary membrane. There is only one genetic study of familial microcoria in the literature. Linkage analysis in a large French pedigree indicated that the gene is located on the long arm of chromosome 13 (13q31–q32). In this paper we report pupillographic and genetic studies in two new families with inherited microcoria; our results suggest there may be both genotypic and phenotypic heterogeneity in this condition.