Early-Onset Retinal Dysfunction Associated with Novel WDR19 Variants in Sensenbrenner Syndrome

TL;DR

A 2-year-old boy with Sensenbrenner syndrome showed early retinal dysfunction linked to new WDR19 gene variants, highlighting the need for early eye screening in this condition.

Contribution

The study reports two novel WDR19 variants and emphasizes early retinal dysfunction in Sensenbrenner syndrome.

Findings

Novel compound heterozygous WDR19 variants c.1778G>T and c.3536T>G were identified in a CED patient.

Early-onset retinal dysfunction was detected via severely reduced ERG responses and optic nerve hypoplasia.

The case underscores the importance of ophthalmologic screening for early detection in CED.

Abstract

Sensenbrenner syndrome, or cranioectodermal dysplasia (CED), is a rare autosomal recessive ciliopathy characterized by craniofacial, skeletal, ectodermal, and renal abnormalities. Ocular involvement, though infrequent, can include retinal dystrophy with early-onset visual impairment. We report a case of a 2-year-old boy with classic clinical features of CED and significant ocular findings. Genetic testing revealed two novel compound heterozygous variants in the WDR19 gene—c.1778G>T and c.3536T>G—expanding the known mutational spectrum associated with this condition. Ophthalmologic evaluation demonstrated bilateral optic nerve hypoplasia, high hyperopia, and severely reduced ERG responses, consistent with global retinal dysfunction. Fundoscopy revealed optic disk pallor, vessel attenuation, and peripheral pigment changes. Multisystem findings included postaxial polydactyly, brachydactyly, short stature, hypotonia, and stage 2 chronic kidney disease. This case highlights the importance of early ophthalmologic screening in suspected CED and underscores the utility of ERG in detecting early retinal involvement. The identification of two previously undescribed WDR19 variants contributes to genotype–phenotype correlation in CED and emphasizes the need for ongoing documentation to guide diagnosis, management, and genetic counseling.

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