NR2F1 and Bosch-Boonstra-Schaaf Optic Atrophy Syndrome Overview
Bosch-Boonstra-Schaaf optic atrophy syndrome (BSOAS) is a disorder characterized by optic atrophy, developmental delay, and intellectual disability. BBSOAS is caused by mutations in the NR2F1 gene, which is located on the long arm of chromosome 5. Each individual receives one copy of this gene from their biological mother and one copy from their biological father. In the vast majority of cases, BBSOAS is inherited de novo, which means that neither parent carries the mutated allele, and the mutation simply occurred as a new event in the sperm or egg when the child was conceived. However, in some cases, BBSOAS can be an inherited disorder and is considered "autosomal dominant," which means that someone who receives a single copy of an abnormal NR2F1 gene from either parent may have this disorder. For someone who has an NR2F1 mutation, their chance of passing it to their children is 50%. If the mutation occurred de novo, and neither parent carries the mutation, the unaffected parents have a <5% chance of having another child affected by an NR2F1 mutation.
BBSOAS is diagnosed through either chromosome microarray, whole exome sequencing, or through NR2F1 sequencing. Once a mutation in NR2F1 has been identified, or a deletion has been found, parents can be tested to determine if the mutation arose de novo or if it was inherited. If the mutation was discovered through trio WES testing, this information may have already been uncovered. As of 2017, over 25 individuals with BBSOAS have been identified, globally. BBSOAS can manifest a wide array of clinical features, but the most common are developmental delay/intellectual disability, vision impairment caused by optic atrophy, hypotonia, and oromotor dysfunction (swallowing problems). A smaller percentage of individuals with BBSOAS have shown hearing loss, seizures, autism spectrum disorder, and thinning of the corpus callosum. There do seem to be genotype-phenotype correlations, which means that the specific type of mutation may tie in with the severity of the clinical manifestations. Of the different types of NR2F1 mutations, it appears that missense mutations in the DNA binding domain cause the most severe phenotypes.
The following tests and therapies are recommended for all patients that have been found to have a mutation in the NR2F1 gene:
1) A brain MRI: recommended at age three or older
2) Full, dilated eye examination from an ophthalmologist every two years
3) Full hearing evaluation every two years
4) Comprehensive psychological evaluation for autism: ADI-R and ADOS testing performed by a certified clinical psychologist
1) Physical Therapy
2) Speech Therapy