Risk factors and genetics in common comitant strabismus: a systematic review of the literature.

IMPORTANCE: Understanding the development of common strabismus is important in locating "at-risk" populations and implementing optimal treatment. This systematic review will bring together reported genetic and environmental risk factors for common strabismus to reveal relationships between risk factors and guide future research.

OBJECTIVE: To identify known environmental and genetic risk factors for comitant strabismus reported in the literature.

DATA SOURCES: A systematic literature search was performed in Medline, Embase, BioSciences Information Service Previews, Web of Science, and the OMIM database during a 2-week period in July 2011 (including all available years) using the following key words: gene, genetic environmental factor, inheritance, risk factor, esotropia, exotropia, strabismus, squint, convergent strabismus, and divergent strabismus.

STUDY SELECTION: No language restrictions were placed on the search. Exclusion criteria consisted of associated syndromes, strabismus not the primary outcome, poor study design or quality, and logarithm of the odds score less than 3.

DATA EXTRACTION AND SYNTHESIS: A study quality and extraction tool was used. Analysis was performed descriptively because of the variant characteristics of the study designs.

MAIN OUTCOMES AND MEASURES: Risk factor, twin, pedigree, and genetic studies.

RESULTS: Forty-one articles fulfilled the inclusion criteria set out by the study, which highlighted 4 subcategories: risk factor, twin, pedigree, and genetic studies. Significant risk factors for strabismus reported by the studies included low birth weight, cicatricial retinopathy of prematurity, prematurity, smoking throughout pregnancy, anisometropia, hyperopia, and inheritance. Inheritance was further supported by twin and pedigree studies, which revealed the complexity of the inheritance pattern. At present the STBMS1 locus is the only gene location that has been supported; however, others have been reported.

CONCLUSIONS AND RELEVANCE: Certain subgroups within the population are at higher risk of developing comitant strabismus and should be identified and monitored to allow for earlier detection. It is evident that a strong hereditary link is present particularly in intermittent and accommodative forms; however, further research is required to identify possible links between subtypes of strabismus. Further genetic research could also help to locate additional causative genes to aid the understanding of strabismus development.