Familial exudative vitreoretinopathy (FEVR) in a child with novel microarray-defined deletion of 11q14 previously diagnosed as retinopathy of prematurity (ROP)

ABSTRACT

Background

Familial exudative vitreoretinopathy (FEVR) is a rare inherited disease characterized by abnormal retinal angiogenesis that leads to incomplete vascularization of the peripheral retina and ischemia. The disease demonstrates complex genetics and can be inherited in an autosomal recessive, autosomal dominant, or X-linked recessive fashion. All presently identified pathogenic genetic variants account for about 50% of all FEVR cases worldwide. Genetic testing can confirm the diagnosis.

Materials and methods

Case report

Case

A 7-year-old female who was born prematurely at 33 weeks gestation and was thought to have progression of bilateral retinopathy of prematurity (ROP) was referred to a pediatric-retina specialist for management. Upon initial examination under anesthesia with multimodal imaging, the diagnosis of FEVR was suspected. Genetic testing identified a FZD4 variant involving a novel complex interchromosomal rearrangement involving chromosomes 2 and 11 associated with microarray-defined deletion of 11q14. The patient was conceived via IVF and has a fraternal twin without FEVR. This is the first report of familial exudative vitreoretinopathy associated with this combination of genetic findings.

Conclusion

Autosomal dominant FEVR involves abnormalities in several genes, including FZD4 at the chromosome 11q. We recommend that patients with microarray-defined deletions of 11q have careful review of the allelic deletions in Chromosome 11 to determine if FZD4 is included because a loss of function variant of a single copy of FZD4 is sufficient to cause the FEVR phenotype. It is essential to differentiate FEVR from other pediatric retinal diseases in children, including ROP, persistent fetal vasculature, and Coats disease.

KEYWORDS:

• FEVR
• familial exudative vitreoretinopathy
• novel variant
• pediatric retina
• retinopathy of prematurity

Acknowledgments

The authors would like to thank Gisselle De Oliveira, photographer of the pediatric retina department at Bascom Palmer Eye Institute.

Consent

Parents signed written consent for the patient to participate in this case report.

Disclosure statement

The authors alone are responsible for the content and writing of this article. Dr. Berrocal has financial interests in Aerie Pharmaceuticals, ProQR therapeutics, Oculus surgical, Alcon, Allergan, DORC, and Zeiss, Novartis.

Additional information

Funding

This work was supported by NIH Center Core Grant P30EY014801, Research to Prevent Blindness- Unrestricted Grant (GR004596).