Bosch-Boonstra-Schaaf Optic Atrophy Syndrome

A number sign (#) is used with this entry because Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is caused by heterozygous mutation in the NR2F1 gene (132890) on chromosome 5q15.

Description

Bosch-Boonstra-Schaaf optic atrophy syndrome is an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy. Most patients also have evidence of cerebral visual impairment. Dysmorphic facial features are variable and nonspecific (summary by Bosch et al., 2014).

Clinical Features

Bosch et al. (2014) reported 6 unrelated patients with optic nerve atrophy associated with developmental delay and intellectual disability (IQ range, 48-74). The patients ranged in age from 2 to 35 years. All had decreased visual acuity, often with visual field defects. Ophthalmologic examination showed variable optic disc abnormalities, including small discs, pale discs, and disc excavation. Five of the patients reportedly had cerebral visual impairment. Other ocular anomalies included strabismus and latent nystagmus. All patients had variable dysmorphic features, but there was no constant pattern. Dysmorphic features included protruding ears, helical anomalies, small nasal ridge, high nasal bridge, upturned nose, epicanthal folds, upslanting palpebral fissures, and tapering fingers. Two patients had hypotonia, and 1 adult patient had severe obsessive-compulsive disorder and autistic features.

Inheritance

The inheritance pattern of Bosch-Boonstra-Schaaf optic atrophy syndrome is autosomal dominant (Bosch et al., 2014).

Molecular Genetics

In 4 patients with cortical visual impairment and intellectual disability, Bosch et al. (2014) identified 4 different de novo heterozygous missense mutations in the NR2F1 gene (132890.0001-132890.0004). Two additional patients with a similar disorder had heterozygous deletions of chromosome 5q (0.83 Mb and 2.85 Mb, respectively) encompassing the NR2F1 gene. In vitro functional expression assays with a luciferase reporter in HEK293 cells showed that all the missense mutations had significantly decreased transcriptional activity compared to wildtype. The findings suggested haploinsufficiency as the pathogenetic mechanism for the disorder.