Table 3.

Genes of Interest in the Differential Diagnosis of NDP-Related Retinopathies

Gene(s)DisorderMOIOverlapping Clinical Feature(s)Comment
ATOH7 Autosomal recessive PFV (OMIM 221900)ARPFVTo be considered in diffdx of PFV
CAPN5 Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) (OMIM 193235)ADCataract, synechiae, retinal neovascularization, vitreoretinal traction, fibrovascular proliferation, vitreous hemorrhage, tractional retinal detachment, phthisis, & loss of light perception in late stagesSignificant uveitis is a hallmark finding in ADNIV (not seen in ND). There are no findings at birth in ADNIV: early signs can be detected in adolescents, but most persons w/ADNIV present as adults.
CTNNB1 CTNNB1-related neurodevelopmental disorder (NDD) 1ADAssoc w/exudative vitreoretinopathy in some personsCTNNB1-related NDD is assoc w/mild-to-profound cognitive impairment in all persons. Other common findings: truncal hypotonia, peripheral spasticity, dystonia, behavioral issues, microcephaly, & refractive errors & strabismus.
CTNNB1
FZD4
LRP5
TSPAN12
ZNF408 		Nonsyndromic FEVR (OMIM PS133780)AD
AR 2		FEVR, retinal detachment, retinal vascular abnormalitiesGenes should be incl in targeted panel for FEVR.
KIF11 Microcephaly-lymphedema-chorioretinopathy (OMIM 152950)ADFEVRKIF11 pathogenic variants can cause nonsyndromic ocular findings or be assoc w/microcephaly, peripheral lymphedema, DD, & brain anomalies.
LRP5 Osteoporosis pseudoglioma syndrome (OMIM 259770)ARPseudoglioma, FEVR; common to have severe exudative vitreoretinopathy & congenital blindnessLow bone density & fractures are not typical in ND.
RB1 Retinoblastoma (RB)ADLeukocoria, pseudoglioma, cataract, strabismusRB must be considered in diffdx of ND, esp in setting of unilateral pseudoglioma. Fundoscopic exam by retina specialist &/or ocular oncologist can distinguish between RB & ND. Ultrasonography & head CT imaging show highly reflective foci in RB, consistent w/calcium deposits.

AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; diffdx = differential diagnosis; MOI = mode of inheritance; FEVR = familial exudative vitreoretinopathy; ND = Norrie disease; PFV = persistent fetal vasculature

1.
2.

Inheritance is autosomal dominant with the exception of LRP5-related FEVR, which can be inherited in an autosomal dominant or autosomal recessive manner (OMIM 601813).

From: NDP-Related Retinopathies

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