CTNNB1 Neurodevelopmental Disorder

Clinical characteristics: CTNNB1 neurodevelopmental disorder (CTNNB1-NDD) is characterized in all individuals by mild-to-profound cognitive impairment and in up to 39% of reported individuals by exudative vitreoretinopathy, an ophthalmologic finding consistent with familial exudative vitreoretinopathy (FEVR). Other common findings include truncal hypotonia, peripheral spasticity, dystonia, behavior problems, microcephaly, and refractive errors and strabismus. Less common features include intrauterine growth restriction, feeding difficulties, and scoliosis.

Diagnosis/testing: The diagnosis of CTNNB1-NDD is established in a proband with suggestive findings and a heterozygous pathogenic variant in CTNNB1 identified by molecular genetic testing

Management: Treatment of manifestations: There is no curative treatment. Supportive care by a multidisciplinary team often includes a neurologist, speech-language pathologist, physiatrist, occupational therapist, physical therapist, feeding team, pediatric ophthalmologist, audiologist, and developmental pediatrician.

Surveillance: Monitor neurologic findings for response to supportive interventions and emergence of new findings or concerns regarding developmental/educational progress, behavior issues, ophthalmologic findings and vision, and family support.

Genetic counseling: CTNNB1-NDD is an autosomal dominant disorder typically caused by a de novo pathogenic variant. Rarely, individuals diagnosed with CTNNB1-NDD inherited a CTNNB1 pathogenic variant from a parent. Once the CTNNB1 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.