LOXL3-related foveal hypoplasia in siblings

To report foveal hypoplasia and high myopia in siblings who harbored biallelic pathogenic variants in the gene LOXL3 (lysyl oxidase-like 3; biallelic) and highlight LOXL3 as a candidate gene for this phenotype.

Retrospective case series.

Two siblings, a 12-year-old boy and his 2-year-old sister, had foveal hypoplasia in the setting of high myopia. Whole exome sequencing revealed both to be homozygous for NM_032603.5: LOXL3 (lysyl oxidase-like 3) c.1036C>T; p.Arg346Trp and NM_000315.4: PTH (parathyroid hormone) c.128 G>A; p.Gly43Glu. The LOXL3 variant has previously been associated with Stickler syndrome; however, phenotypic reassessment did not reveal hearing loss, flat facies, palatal or skeletal abnormalities, or the vitreous phenotype of classic Stickler syndrome. The PTH variant was consistent with pseudohypoparathyroidism. The boy had been previously diagnosed with this by an endocrinologist, and phenotypic reassessment confirmed the same diagnosis in his sister.

Biallelic LOXL3 pathogenic variants should be considered in the differential diagnosis of foveal hypoplasia with high myopia.