Bilateral sclerocornea in an infant with molecularly confirmed Van den Ende–Gupta syndrome due to a recurrent SCARF2 founder variant: a case report and review of ophthalmic manifestations

Abstract

PURPOSE: Van den Ende-Gupta syndrome (VDEGS) is a rare autosomal recessive disorder caused by biallelic variants and characterized by blepharophimosis, arachnodactyly, congenital joint contractures, and a recognizable craniofacial phenotype, with normal growth and intelligence. The ophthalmic phenotype beyond blepharophimosis is sparsely described, and sclerocornea has been reported in only two molecularly confirmed patients to date. We describe the ocular phenotype of a 7-month-old male infant with molecularly confirmed VDEGS due to a recurrent Saudi founder variant. METHODS: A single case report of a 7-month-old male of consanguineous Saudi parents referred for photophobia and small-appearing eyes, coupled with a focused review of the published ophthalmic phenotype of VDEGS. RESULTS: Examination revealed bilateral blepharophimosis with epicanthus inversus and bilateral, asymmetric peripheral sclerocornea with loss of limbal demarcation and no vascularization, with a symmetric and good red reflex bilaterally. Cycloplegic refraction demonstrated clinically significant spherical hyperopic anisometropia (+6.00 OD versus +3.00 OS) placing the patient at substantial risk for anisometropic amblyopia, a refractive finding not previously documented in VDEGS. The visual axis was not entirely obscured, and the patient maintained good following and fixation in both eyes. Whole-exome sequencing identified a homozygous pathogenic variant (NM_153334.7: c.190T>C, p.(Cys64Arg)), a recurrent Saudi founder allele, confirming the diagnosis of VDEGS. CONCLUSION: This report expands the ocular phenotype associated with the recurrent c.190T>C founder variant to include bilateral peripheral sclerocornea and clinically significant hyperopic anisometropia, further supporting biallelic dysfunction as sufficient to disrupt anterior segment development.