Familial strabismus in Sardinia

Purpose: Strabismus, a manifest misalignment of the visual axes, is one of the most common childhood visual disorders, occurring in 3-4% of the population. It is the most common cause of amblyopia and an important contributor to childhood visual impairment. Very little is known about the pathogenesis of strabismus and about the more common childhood form of strabismus, concomitant strabismus (CS).We analyzed all the cases of familial CS observed in the last ten years, in order to define the number of affected families, the phenotype of affected members and to provide DNA for genetic studies. Methods: The clinical files of concomitant strabismus patients examined at the Strabismus Unit of the University Eye Clinic of Cagliari were reviewed for this study. All cases positive for familial history of CS were selected, and asked to participate to this study, which included a new ophthalmic evaluation for all family members of the proband. Informed consent to participate in the study was taken from probands and legal guardians. Ophthalmic examinations included visual acuity, angles of deviation at distance and near with cover-uncover test, alternate prism cover test or Krimsky test, stereopsis test and cycloplegic refraction. Results: We ascertained 68 probands related to 62 families in which two or more patients affected by CS were present. From these 62 families, 195 patients were diagnosed to be affected by CS. Most of these families were located in the southern part of the island. Most of the patients (77.9%) showed esotropia, with respect to exotropia (22.1%). In esotropic patients, 64.2% had an accommodative component, 22.6% intermittent esotropia, and 13.2% essential infantile esotropia. In exotropic patients, we found 53.3 % of constant forms, with respect to 46.7% of intermittent forms. In families with esotropia with accommodative component an autosomal recessive trait was observed in 59.5% of cases, an autosomal dominant trait in 20.6% of cases, and it was undetermined in the remaining cases. In intermittent esotropia, an autosomal dominant trait with incomplete penetrance was observed in 41.6% of cases, and an autosomal dominant trait in 25% of cases. In esotropia, 50% of families with constant forms showed an autosomal dominant trait, 25% autosomal recessive and 25% was undetermined; in intermittent esotropia, 57.1% of families showed an autosomal dominant trait, 28.6% an autosomal recessive trait, and 14.3% was undetermined. Conclusions: This study reveals that in a number of families with CS the disease is trasmitted as a mendelian autosomal recessive or dominant trait. Such family pedigrees may be useful for DNA analysis of strabismus.