NR2F1-Related Neurodevelopmental Disorder

Excerpt

Clinical characteristics: NR2F1-related neurodevelopmental disorder (NR2F1-NDD) is characterized by developmental delay / intellectual disability (ranging from profound to mild) and is commonly associated with hypotonia, visual impairment (due to optic nerve abnormalities and/or cerebral visual impairment), epilepsy, and behavioral manifestations (e.g., autism spectrum disorder, attention-deficit/hyperactivity disorder).

Diagnosis/testing: The diagnosis of NR2F1-NDD is established in a proband with suggestive findings and a heterozygous pathogenic (or likely pathogenic) variant in NR2F1 identified by molecular genetic testing.

Management: Treatment of manifestations: There is no cure for NR2F1-NDD. Supportive treatment typically relies on multidisciplinary specialists in the fields of neurology, speech-language pathology, ophthalmology (including low-vision services), gastroenterology, nutrition, occupational therapy, physical therapy, audiology, clinical genetics, and genetic counseling.

Surveillance: Regular monitoring of existing manifestations, the individual's response to supportive care, and the emergence of new manifestations.

Genetic counseling: NR2F1-NDD is an autosomal dominant disorder. Most probands reported to date with an intragenic NR2F1 pathogenic variant whose parents have undergone molecular genetic testing have the disorder as the result of a de novo pathogenic variant. Some recurrences within a family have been reported. Risk to future pregnancies is presumed to be low when the proband has what appears to be a de novo NR2F1 pathogenic variant; however, there is a recurrence risk (~1%) to sibs based on the theoretic possibility of parental germline mosaicism. Given this risk, prenatal and preimplantation genetic testing may be considered.