To characterize ocular phenotypes in patients with CTNNB1, KIF11, or NDP variants.

Retrospective case series.

Seventy-four patients from 59 unrelated families with CTNNB1, KIF11, and NDP variants were enrolled based on exome sequencing. The clinical data of ophthalmoscope, fundus photography, fluorescein angiography, and ocular ultrasound scan were evaluated.

A total of 55 potential pathogenic variants were identified, including 26 in KIF11 (28 families), 23 in NDP (25 families), and 6 in CTNNB1 (6 families). In total, 74 patients from the 59 families carried the variants, in whom clinical data were available from 70 patients for the current analysis. Severe familial exudative vitreoretinopathy (FEVR), stages 4 and 5, was present in 72.9% (51/70) of patients. In addition, panretinal or sector chorioretinal degeneration along with FEVR is a specific feature associated with KIF11 variants, present in 93.8% (30/32) of patients. FEVR-like change was observed in almost all patients with rare hemizygous variants in NDP, patients with heterozygous truncation variants in CTNNB1, as well as patients with heterozygous truncation or damaging missense variants in KIF11.

Severe FEVR-like change with or without significant chorioretinopathy is a common feature in addition to neurodevelopmental disorders for variants in CTNNB1, KIF11, and NDP. In our cohort, the frequency of families with variants in KIF11 was comparable to that in TSPAN12, so as for NDP. Recognizing the characteristics of variants in the 3 genes and associated ocular phenotypes may enrich our understanding and potential management of this disease.