Familial unilateral Brown syndrome

Purpose: To report a family in which three siblings have unilateral late-onset Brown syndrome. Methods: The entire nuclear family underwent ophthalmologic evaluation. Orbital imaging and systemic workup were obtained to rule out local or systemic causes. Historic information was obtained from unavailable family members. The family's Brown syndrome trait was analyzed for linkage to the known congenital fibrosis syndrome loci and the CFEOM2 gene, ARIX, was sequenced in affected individuals. Results: All affected siblings developed left-sided Brown syndrome, worse on awakening, at 12-13 years of age. No evidence of Brown syndrome could be identified in other family members, either by exam or history. No abnormalities of the trochlear-tendon complex could be documented. Haplotype analysis of the Brown syndrome phenotype was consistent with recessive inheritance at the DURS1 locus and dominant inheritance with reduced penetrance at the DURS1, DURS2, and FEOM1 loci. No mutations were detected in CFEOM2 gene, ARIX. Conclusions: We propose that a genetically determined predisposition to Brown syndrome is likely responsible for the observed manifestations in this family and that late age of onset and intermittent manifestations do not distinguish acquired from hereditary Brown syndrome. The pattern of inheritance of the Brown phenotype in this family could be either autosomal recessive or autosomal dominant with reduced penetrance. Our analysis only permitted the exclusion of the FEOM3 locus and the FEOM2 gene, ARIX. Future genetic studies of additional Brown syndrome families should shed additional light on the genetic basis of this disorder.