Familial blepharophimosis-like syndrome with esotropia, uveal coloboma, and short stature

Abstract

Background: Interstitial deletion of Hsa 3q involves FOXL2, the gene responsible for blepharophimosis-ptosis-telecanthus-epicanthus inversus (BPES). Thought to be due to a contiguous gene syndrome, the recognizable phenotype of 3q interstitial deletion includes BPES facies and has not been associated with other loci.

Objective: To describe a familial syndrome that resembles the interstitial deletion of 3q clinically, but does not map to the FOXL2 region.

Methods: Clinical evaluation of family members and linkage analysis.

Results: Three affected siblings with a phenotype resembling that seen in 3q interstitial deletion were studied in addition to their clinically unaffected parents. Linkage analysis excluded FOXL2 as underlying the distinct phenotype, observed with > 99% confidence.

Conclusions: The relevant locus in the current family, although remote from FOXL2, is likely important to the FOXL2 functional pathway. The phenotype observed in 3q interstitial deletion may be due to severe disruption of FOXL2 rather than to a contiguous gene syndrome.