Genetics of strabismus

Abstract

Strabismus, or misalignment of the eyes, is the most common ocular disorder in the pediatric population, affecting approximately 2%–4% of children. Strabismus leads to the disruption of binocular vision, amblyopia, social and occupational discrimination, and decreased quality of life. Although it has been recognized since ancient times that strabismus runs in families, its inheritance patterns are complex, and its precise genetic mechanisms have not yet been defined. Family, population, and twin studies all support a role of genetics in the development of strabismus. There are multiple forms of strabismus, and it is not known if they have shared genetic mechanisms or are distinct genetic disorders, which complicates studies of strabismus. Studies assuming that strabismus is a Mendelian disorder have found areas of linkage and candidate genes in particular families, but no definitive causal genes. Genome-wide association studies searching for common variation that contributes to strabismus risk have identified two risk loci and three copy number variants in white populations. Causative genes have been identified in congenital cranial dysinnervation disorders, syndromes in which eye movement is limited or paralyzed. The causative genes lead to either improper differentiation of cranial motor neurons or abnormal axon guidance. This article reviews the evidence for a genetic contribution to strabismus and the recent advances that have been made in the genetics of comitant strabismus, the most common form of strabismus.

Mental Health Conditions Associated With Strabismus in a Diverse Cohort of US Adults

“…Unfortunately, the genetics of strabismus, particularly nonsyndromic strabismus, remain poorly understood. Family and twin studies support a heritable component to strabismus, but the contributing genes remain elusive . To date, only 2 loci have been identified through genome-wide association studies: a functional single-nucleotide variation in an intron of WRB (also known as GET1 ; OMIM 602915) on chromosome 21, first identified in nonaccommodative esotropia and replicated in all forms of strabismus and divergent strabismus, and the NPLOC4 (OMIM 606590) –TSPAN10 (Genbank 83882)– PDE6G (OMIM 180073) gene cluster, first reported in self-reported strabismus and replicated in all forms of strabismus, convergent strabismus, and divergent strabismus.…”

Presence of Copy Number Variants Associated With Esotropia in Patients With Exotropia

“…Monogenic causes have been identified for specific paralytic strabismus syndromes, but genetic causes for the common, concomitant forms of developmental horizontal strabismus have not been identified. Twin, family, and population studies all support a genetic contribution to developmental strabismus . Several environmental risk factors for common horizontal strabismus have also been identified, including low birth weight, prematurity, maternal smoking during pregnancy, and advanced maternal age.…”