Pedigree Analysis of Familial Primary Concomitant Horizontal Strabismus in Northern India

Abstract

Purpose: Familial clustering of common forms of primary strabismus like esotropia (ET) and exotropia (XT) is observed in a proportion of the strabismus cohort. The genetic components of this remain unidentified. Linkage studies have demonstrated susceptibility locus for primary strabismus at the STBMS1 locus on 7p22.1 as well as other loci on 4q28.3 and 7q31.2. Recently next generation sequencing (NGS) technology has emerged as a powerful tool in discovery genomics and a large number of novel disease-causing variants are being reported. In this study, we recruited informative families for subsequent genetic analysis for disease-causing variant identification. Methods: All consecutive families with two or more affected members with primary concomitant horizontal strabismus were prospectively recruited at the ophthalmic outpatients department (OPD) of Lady Hardinge Medical College, New Delhi, from August 2014 to February 2017. Detailed phenotypic evaluation and pedigree documentation was performed. Results: Of the 39 recruited families of north Indian origin, 18 families each had affected family members demonstrating either ET or XT. 100% concordance of the phenotype in the affected family members was observed in these families. While vertical transmission was observed in 17/18 families with XT, 7 with ET had affected members across one generation, 2 demonstrated consanguineous pedigree, and 2 comprised identical twin families. In 3 families, a combination of ET and XT was noted. This comprised one family with the ET and XT patients being from 2 separate arms of the family related by marriage, one family where one sibling had XT and the other had ET, and another family where the maternal aunt of the affected proband with ET had XT. Conclusions: Subjects with familial primary concomitant strabismus recruited in this study may provide a valuable resource to unravel the genetic determinants of this condition, which is a common disorder of early childhood with high ophthalmic morbidity.