A novel frameshift variant in the GJA1 gene is associated with recessive oculodentodigital dysplasia.

Background: Oculodentodigital dysplasia (ODDD) is a rare syndrome that causes a constellation of facial, ophthalmic, dental, and limb abnormalities. Variants in the gap junction alpha-1 (GJA1) gene have been described in patients with ODDD. Hereby we present the ocular manifestations in a patient with recessive ODDD due to a novel homozygous frameshift variant in GJA1.

Material and methods: Detailed ophthalmic manifestation and clinical features of disease were documented through external color photography and ultrasound biomicroscopy (UBM). Genetic testing was performed through a congenital heart disease panel.

Results: A six-year-old girl was referred for ophthalmic evaluation in the setting of numerous syndromic features compatible with ODDD. Clinical features included nasal thinning, alar hypoplasia, hypotrichosis, microdontia and enamel hypoplasia. Ocular manifestations included microcornea, microphthalmia, posterior synechiae, cataract, and persistent hyperplastic primary vitreous. Genetic testing revealed a novel homozygous variant in the GJA1 gene, c.565del p.(Arg189Glufs *35). This variant disrupts the fourth helical transmembrane domain of the protein as well as its C-terminal cytoplasmic tail.

Conclusion: Here we describe the clinical and ocular manifestations of a Brazilian patient with ODDD, report a novel frameshift homozygous variant in GJA1, and contribute to the ongoing expansion of scientific knowledge regarding ODDD.