Dual phenotype: co-occurring Leber congenital amaurosis and familial exudative vitreoretinopathy: a case report

ABSTRACT

Purpose

To report the concurrent presentation and management of IQCB1-associated Leber Congenital Amaurosis and NDP-associated Familial Exudative Vitreoretinopathy (FEVR).

Materials and Methods

A 6-month-old Caucasian infant presented with poor visual response, high hypermetropia, and infantile-nystagmus with a provisional diagnosis of Leber Congenital Amaurosis based on clinical findings. Genetic counseling and testing were performed with a 285 gene retinal dystrophy panel (Blueprint Genetics). Clinical characteristics, presentation, ancillary testing results, and management are described.

Results

Two previously reported heterozygous pathogenic variants in ICQB1 were identified (c.1518_1519del (p.His506Glnfs*13) and c.1381C>T, p.Arg461*) segregating in trans. In addition, a variation of uncertain significance (VUS) was found in NDP (c.280C>T; p.His94Tyr). Fluorescein angiography was performed demonstrating peripheral avascularity and retinal telangiectasia without frank neovascularization. Peripheral ablative laser was applied to the avascular zone.

Conclusions

The NDP VUS likely represents a pathogenic variant given the FEVR phenotype in addition to retinal degeneration, creating a rare dual phenotype. The combination of low oxygen demand from the IQCB1-associated retinal degeneration and NDP variant may have led to a more attenuated FEVR presentation with uncertain prognosis. A molecular diagnosis informed ocular and renal surveillance, as well as the recurrence risk for future offspring.

KEYWORDS:

• Dual phenotype
• familial exudative vitreoretinopathy
• IQCB1
• Leber congenital amaurosis
• NDP
• Norrie disease
• variant of uncertain significance
• incidental finding

Disclosure statement

The authors have no financial conflicts of interest regarding this manuscript.

Drs. Utz, Ebert, Brightman, Benoit, and Simpson do not have any disclosures. Dr. Sisk is a consultant for Applied Genetic Technologies Corporation, Allergan, EyePoint, Gyroscope, Leica Microsystems, Orbit Biomedical, and RegenXBio.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13816810.2022.2090011.

Additional information

Funding

The author(s) reported that there is no funding associated with the work featured in this article.