Missense variants in CTNNB1 can be associated with vitreoretinopathy-Seven new cases of CTNNB1-associated neurodevelopmental disorder including a previously unreported retinal phenotype.

BACKGROUND: CTNNB1 (MIM 116806) encodes beta-catenin, an adherens junction protein that supports the integrity between layers of epithelial tissue and mediates intercellular signaling. Recently, various heterozygous germline variants in CTNNB1 have been associated with human disease, including neurodevelopmental disorder with spastic diplegia and visual defects (MIM 615075) as well as isolated familial exudative vitreoretinopathy without developmental delays or other organ system involvement (MIM 617572). From over 40 previously reported patients with CTNNB1-related neurodevelopmental disorder, many have had ocular anomalies including strabismus, hyperopia, and astigmatism. More recently, multiple reports indicate that these abnormalities are associated with the presence of vitreoretinopathy. METHODS: We gathered a cohort of three patients with CTNNB1-related neurodevelopmental disorder, recruited from both our own clinic and referred from outside providers. We then searched for a clinical database comprised of over 12,000 exome sequencing studies to identify and recruit four additional patients. RESULTS: Here, we report seven new cases of CTNNB1-related neurodevelopmental disorder, all harboring de novo variants, six of which were previously unreported. All patients but one presented with a spectrum of ocular abnormalities and one patient, who was found to carry a missense variant in CTNNB1, had notable vitreoretinopathy. CONCLUSIONS: Our findings suggest ophthalmologic screening should be performed in all patients with CTNNB1 variants.

Living with a child at risk for psychotic illness: the experience of parents coping with 22q11 deletion syndrome: an exploratory study.

Patients with 22q11 deletion syndrome (22q11DS) have a 25-30% risk of developing schizophrenia, as well as an increased risk for other psychiatric illnesses including bipolar and schizo-affective disease. As a result, their families may be informed of a risk for psychotic illness years or even decades before the likely age of onset. We performed an exploratory study, surveying 41 caretakers of individuals with 22q11DS, and found that information about the association between 22q11DS and psychiatric disease was omitted at diagnosis a majority of the time and rarely addressed subsequently by pediatricians or other medical specialists, including medical geneticists. Families frequently received their information only from non-medical sources, principally the Internet. Individuals with 22q11DS often have many medical issues, but a majority of parents indicated that the risk of psychotic illness was their greatest source of anxiety. Looking at how predictive information affects those who receive it is an important adjunct to the development of genetic testing; the experience of these families suggests that in order to use the information to improve outcomes or modify risk it is necessary to receive it in the context of ongoing support and access to resources.