Genetic findings and clinical features of extreme refractive errors in Thai children using whole genome sequencing

Extreme refractive errors in children may indicate underlying genetic or syndromic conditions. This study investigated the genetic basis of high refractive errors in Thai children and compared clinical characteristics between high myopia and high hyperopia, and identified clinical predictors of a positive genetic result.

Ninety-eight children (<18 years) with high refractive errors were recruited from the Queen Sirikit National Institute of Child Health. All underwent comprehensive ophthalmic examination; ocular biometry and optical coherence tomography (OCT) were performed when feasible. Whole genome sequencing was performed, and variants were interpreted using established clinical classification frameworks. Clinical characteristics were compared between gene-positive and gene-negative patients.

Among 98 children (mean age 8.7 ± 4.0 years; 52% male), 71 had high myopia and 27 had high hyperopia. Pathogenic or likely pathogenic variants were identified in 23.94% of myopic and 29.63% of hyperopic patients. In the myopic group, variants in COL2A1 and COL11A1 were most frequent. In the hyperopic group, variants in PRSS56 and MFRP were associated with posterior microphthalmos or nanophthalmos. A positive family history was 2.6-fold more common in gene-positive myopic patients (p = 0.012), and OCT abnormalities were exclusively observed in gene-positive hyperopic patients (p < 0.001).

Extreme refractive errors in children are genetically heterogeneous and often associated with monogenic conditions. A positive family history and OCT abnormalities are clinically useful indicators to guide genetic testing. Genetic testing in selected patients may improve diagnosis and support surveillance for complications such as retinal detachment and glaucoma.