Background: Oculoskeletodental syndrome (OCSKD) is a rare autosomal recessive ciliopathy caused by PIK3C2A loss-of-function variants, characterized by ocular, skeletal, and dental anomalies. Ocular findings most commonly include cataract and secondary glaucoma; however, high axial myopia and megalocornea have not been previously reported in the literature.
Case presentation: We report a 2-year-old girl with OCSKD who presented with severe high axial myopia, bilateral megalocornea, lamellar cataracts, and developmental delay. Systemic evaluation revealed short stature and dental enamel hypoplasia. Clinical exome sequencing and whole mitochondrial genome sequencing identified a homozygous pathogenic variant in exon 8 PIK3C2A(NM_002645.4;ENST000000265970.11):c.1733_1736del(p.lle578LysfsTer3); NC_000011.10:g.17136594_17136597del [GRCh38]. The variant was classified as pathogenic and predicted to be damaging by MutationTaster2. Prenatal Sanger variant analysis testing of amniotic fluid in a fetus (to be the sibling of the index patient) showed the same variant in heterozygous form, confirming autosomal recessive inheritance.
Conclusion: This case highlights phenotypic variability in PIK3C2A-related oculoskeletodental syndrome and raises the possibility of additional ocular involvement. Early molecular diagnosis enables accurate genetic counseling and supports targeted prenatal testing in affected families.
Keywords: High myopia; cataract; dental anomalies; genetic testing.