Genetics of non-syndromic strabismus: a systematic review
Maliheh Rahpeyma1 , Amirsaeed Aghabozorgi1 , Mohammad Yaser Kiarudi2 *, Aliakbar Sabermoghaddam2 , Alireza Pasdar1
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Abstract: Strabismus is a common ocular problem and may be accompanied by abnormal movement of one or both eyes, decreased and double vision, and also abnormal head posture. Genetic factors play a role in the development of strabismus, hence, strabismus can be divided into syndromic and nonsyndromic. Family studies demonstrated inheritance patterns of dominant, recessive, and sex-linked for nonsyndromic strabismus. Some studies suggested specific candidate genes which are thought to be effective in the development of non-syndromic strabismus. Ocular misalignment which is normally non-paralytic and non-restrictive with a similar magnitude of gaze in all directions (comitant) is the main feature of non-syndromic strabismus. The aim of this study was to systematically search for the genetic background of strabismus.
Methods: A literature search was performed using keywords (“strabismus” OR "squint" OR "eye misalignment" OR "esotropia" OR "esophoria" OR "exotropia" OR "exophoria") AND (genetics OR Mutation OR variations OR familial). PubMed, Scopus, and Web of Science up to April 2021(including all available years) were searched. Languages other than English were excluded.
Reference lists of included studies were also reviewed for additional articles. All possible case-control, linkage analysis, proteomics, and gene expression studies, as well as sequencing analysis, were included for review.
Results: Based on search criteria, 373 papers were initially included. Finally, twenty eligible full original articles were reviewed. In most studies, linkage analysis had been performed which showed no definite association for non-syndromic strabismus in an Asian population. However, an association between a susceptibility locus (7p22.1) and non-syndromic strabismus as well as esotropia in association with hyperopia in a Caucasian population has been reported.
Conclusion: Various loci and genes have been reported related to non syndromic strabismus in Asian, Middle Eastern, and Caucasian populations which indicate the heterogeneous nature of the disease. The reports indicate that there is at least one non-syndromic strabismus associated genetic component at the STBMS1 locus. Despite substantial advances in genetic testing, only few studies used whole genome sequencing (WGS) to identify related genetic background for strabismus.
