Severe Familial Exudative Vitreoretinopathy, Congenital Hearing Loss, and Developmental Delay in a Child With Biallelic Variants in FZD4.
JAMA Ophthalmol
; 140(9): 889-893, 2022 09 01.
Article
en En
| MEDLINE
| ID: mdl-35951321
ABSTRACT
Importance Familial exudative vitreoretinopathy (FEVR) is a nonsyndromic autosomal dominant retinal disorder commonly caused by variants in the FZD4 gene. This study investigates the potential role beyond ocular abnormalities for FZD4 gene variants in patients with FEVR. Objective:
To evaluate the role of FZD4 in symptoms beyond those associated with FEVR through a patient with biallelic variants in FZD4. Design, Setting, andParticipants:
This case series included the DNA testing and phenotyping of 1 patient proband and her parents, combined with signaling assays, to determine the association of patient-derived compound heterozygous variants on FZD4 signaling and biologic function. Main Outcomes andMeasures:
FZD4 genes were tested using next-generation sequencing and Sanger sequencing. Cell-based assays measured the effect of the variants on FZD4 signaling.Results:
The proband presented with absent red reflexes from complete tractional retinal detachments diagnosed at 3 days of age and failed the newborn screening hearing test. Auditory brainstem response at 6 months of age showed bilateral mild to moderate high-frequency sensorineural hearing loss. The patient manifested developmental delays in speech and walking. Intravenous fluorescein angiography (IVFA) of the patient's parents detected stage 1 FEVR. Genetic testing revealed 2 FZD4 variants in the patient, each variant found in 1 parent. Signaling assays confirmed that the presence of both variants was associated with significantly worse signaling activity compared with the heterozygous state. Conclusions and Relevance Results of this case series suggest that extraocular syndromic FEVR was associated with FZD4 variants. The decrease in FZD4 signaling owing to the biallelic nature of the disease resulted in hearing deficits, developmental delays, and a more severe retinal phenotype.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades de la Retina
/
Productos Biológicos
/
Enfermedades Hereditarias del Ojo
/
Pérdida Auditiva Sensorineural
Tipo de estudio:
Diagnostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
JAMA Ophthalmol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Canadá