Severe Familial Exudative Vitreoretinopathy, Congenital Hearing Loss, and Developmental Delay in a Child With Biallelic Variants in FZD4

• DOI: 10.1001/jamaophthalmol.2022.2914
• Publication Date: 2022-08-19T16:01:18Z
• Authors: Sarah R. van der ...; Benjamin S. Meyers; Jenina E. Capasso; Mario Sasongko; Yoshihiro Yonekawa; Matthew Pihlblad; Jennifer Huey; Emma C. Bedoukian; Ian D. Krantz; Michael H. Ngo; Christopher R. Mc...; Alex V. Levin; Johane M. Robitaille
• Keywords: Proband; Sanger sequencing; Compound heterozygosity

Familial exudative vitreoretinopathy (FEVR) is a nonsyndromic autosomal dominant retinal disorder commonly caused by variants in the FZD4 gene. This study investigates potential role beyond ocular abnormalities for gene patients with FEVR.To evaluate of symptoms those associated FEVR through patient biallelic FZD4.This case series included DNA testing and phenotyping 1 proband her parents, combined signaling assays, to determine association patient-derived compound heterozygous on biologic function.FZD4 genes were tested using next-generation sequencing Sanger sequencing. Cell-based assays measured effect signaling.The presented absent red reflexes from complete tractional detachments diagnosed at 3 days age failed newborn screening hearing test. Auditory brainstem response 6 months showed bilateral mild moderate high-frequency sensorineural loss. The manifested developmental delays speech walking. Intravenous fluorescein angiography (IVFA) patient's parents detected stage FEVR. Genetic revealed 2 patient, each variant found parent. Signaling confirmed that presence both was significantly worse activity compared state.Results this suggest extraocular syndromic variants. decrease owing nature disease resulted deficits, delays, more severe phenotype.