Most mutations (38/41) in
CTNNB1 were identified in 48 families with intellectual disabilities and autism spectrum disorders in previous studies. Of the 48 families, approximately half (20/48) had eye abnormalities. Three mutations in
CTNNB1 were recently identified in eight patients with FEVR from three families, and one of these patients was diagnosed with FEVR at the age of 4 weeks but displayed features of intellectual disability at the age of 3 years.
15 In the current study, four patients with
CTNNB1 mutations exhibited FEVR or Norrie-like retinopathy, and all of them were examined before 1 year of age due to severe visual defects. The follow-up study after the molecular results were obtained showed that three of the four patients exhibited features of systemic anomalies, including autism, learning disability, motor delay, and scoliosis. The other patient was not available (QT409) but displayed features of Norrie disease. In addition to this study, two previous studies identified two mutations in patients with FEVR or retinal detachment accompanied by intellectual disability, developmental delay, and microcephaly.
14,24 Therefore, variable manifestations of FEVR might be part of the phenotypes resulting from
CTNNB1 mutations. This trend is similar to that found for mutations in
KIF11, which have been identified in patients with syndromic and nonsyndromic FEVR. Some patients with mutations in
KIF11 are initially diagnosed with FEVR but found to exhibit mental retardation or microcephaly when reexamined after 17 years of age, potentially because intellectual disability is easily ignored in infants. Moreover, Norrie disease is characterized by fibrovascular masses secondary to similar vascular dysgenesis of the retina accompanied by mental disorders. Mutations in
NDP can cause Norrie disease, and occasionally FEVR. Therefore, similar phenotypes can be caused by mutations in
CTNNB1,
KIF11, and
NDP.