Clinical, Radiologic, and Genetic Features in Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome in the Indian Population

Abstract

To study the clinical, radiologic, and genetic features in Indian Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) patients. A total of 33 clinically well characterized BPES cases who presented between 2009 to 2011 were recruited. Clinical evaluation consisted of ophthalmic and orthoptic examination. For orbital indices, computed tomography (CT) scan of orbits was performed. Genetic studies included cytogenetic analysis and molecular analysis of FOXL2 gene. Significant clinical findings included a high incidence of refractive error in 94%, amblyopia in 60%, and strabismus in 40% of BPES cases. Orbital radiologic indices on CT scan in BPES were found to be comparable to the control group. On karyotyping, 8 out of 33 (24%) cases harbored chromosomal abnormalities. These abnormalities included 46,XY;del(3qter), 46,XY;del(3q26.3), 46,XX;del(3q24-25), and 46,XY;del(3q26qter). On molecular analysis, a novel mutation consisting of heterozygous substitution at c1635 that replaced cytosine by thymidine was detected. To the best of our knowledge, this is the first study on clinical features in BPES patients of Indian origin. A high incidence of refractive error, strabismus, and amblyopia was found in BPES cases. Orbital imaging confirmed that clinical features are limited to soft tissue abnormalities, with no underlying bony changes. Cytogenetic studies showed that most chromosomal abnormalities in the Indian population are in the region of the long arm of chromosome 3. Results of molecular analysis indicate that there may be loci other than the FOXL2 gene, which are affected in BPES cases. Our study expands the existing mutation spectrum of FOXL2 gene.