Bosch-Boonstra-Schaaf
optic atrophy syndrome (BBSOAS) is a recently described autosomal dominant disorder caused by mutations in the
nuclear receptor subfamily 2 group F member 1 (NR2F1) gene. Its common features include
optic atrophy and/or hypoplasia, developmental delay,
intellectual disability,
attention deficit disorder,
autism spectrum disorder,
seizures, hearing defects, spasticity,
hypotonia, and thinning of the corpus callosum. Mitochondrial involvement has also been described with BBSOAS. Currently, 31 cases of BBSOAS have been described in the literature. Here we report a case of undiagnosed BBSOAS presenting as
psychosis in a 32-year-old man with a history of bilateral optic nerve
atrophy,
intellectual disability,
epilepsy, and mitochondrial complex I abnormality on muscle biopsy. Whole-genome sequencing identified a heterozygous de novo
nonsense mutation in the NR2F1 gene [c.253 G>T (
guanine to
thymine mutation in coding position 253) in exon 1, p.E85X variant (GAG>TAG) (
glutamic acid to stop
codon mutation;
protein truncated to 85
amino acids)]. A pathogenic
nonsense mutation has not previously been reported in the literature in association with BBSOAS and represents an expansion of clinically relevant variants.
Psychosis has also not been previously reported in this syndrome and may represent a phenotypic expansion of BBSOAS, a manifestation of prolonged disease, or a result of disease management.