| Domain | Recommended evaluation or therapy | Implementation notes | Suggested MAXO terms and LOINC/imaging modalities | Evidence source |
|---|---|---|---|---|
| Vision | Comprehensive neuro-ophthalmologic examination | Initial workup should document visual impairment, optic nerve anomalies, strabismus/nystagmus, and functional vision; visual impairment in BBSOAS often becomes apparent in early childhood and may be non-progressive on follow-up | MAXO: visual function rehabilitation; Imaging/modalities: fundus photography, optical coherence tomography (OCT), visual evoked potentials (VEP), electroretinography (ERG) (pqac-00000014, pqac-00000015) | Deep phenotyping study of 22 individuals; review and management summary (pqac-00000014, pqac-00000015, pqac-00000013) |
| Vision | Visual therapy focused on cortical visual impairment (CVI) | Recommended supportive intervention when CVI is present; real-world implementation is rehabilitative rather than disease-modifying | MAXO: visual rehabilitation / visual therapy; modality: CVI-focused assessment and therapy (pqac-00000013) | Review with recommended therapeutic approaches table (pqac-00000013) |
| Vision | OCT assessment of retinal ganglion cell layer and RNFL | High-resolution OCT can confirm retinal ganglion cell loss/ganglion cell layer thinning and support distinction between developmental optic nerve hypoplasia and degenerative optic atrophy | Imaging/modality: optical coherence tomography (OCT) of macula/optic nerve head (pqac-00000014, pqac-00000015) | Human cohort with structural ocular phenotyping (pqac-00000014, pqac-00000015) |
| Vision | Electrophysiology of visual pathway | Pattern/flash VEP and ERG are useful to document retinal ganglion cell dysfunction and visual pathway conduction abnormalities | LOINC/imaging modalities: pattern VEP, flash VEP, full-field ERG, pattern ERG (pqac-00000014, pqac-00000015) | Human cohort methods and findings (pqac-00000014, pqac-00000015) |
| Neurology | Brain MRI with attention to corpus callosum, optic pathways, cortical malformations, delayed myelination | Neuroimaging abnormalities are common in reported patients; MRI helps assess syndromic involvement and differential diagnosis | Imaging/modality: brain MRI; diffusion tensor imaging/tractography where available (pqac-00000011, pqac-00000013, pqac-00000014) | Case aggregation/review and ophthalmic-neuroimaging cohort data (pqac-00000011, pqac-00000013, pqac-00000014) |
| Neurology | EEG when seizures/epilepsy or infantile spasms are suspected | Epilepsy is frequent in BBSOAS; EEG is part of workup for seizure phenotypes and can guide anti-seizure treatment | LOINC/modality: electroencephalography (EEG); MAXO: antiseizure medication therapy / anticonvulsive treatment (pqac-00000011, pqac-00000013) | Review of phenotype spectrum and recommended therapies (pqac-00000011, pqac-00000013) |
| Neurology | Anti-convulsive treatment if epilepsy is present | Symptomatic management only; no disease-specific therapy established | MAXO: anticonvulsant treatment / seizure management (pqac-00000013, pqac-00000002) | Review therapeutic table; later case report notes no specific treatment exists beyond symptomatic care (pqac-00000013, pqac-00000002) |
| Development | Developmental assessment for developmental delay/intellectual disability | Evaluate speech, motor, cognition, behavior, adaptive function; DD and ID are among the most common features | MAXO: developmental assessment; neuropsychological evaluation (pqac-00000011, pqac-00000013) | Review synthesizing common features and care recommendations (pqac-00000011, pqac-00000013) |
| Development | Physical therapy | Aims to increase strength and improve gross motor skills, especially relevant for hypotonia/poor coordination | MAXO: physical therapy (pqac-00000013) | Review therapeutic table (pqac-00000013) |
| Development | Occupational therapy | Aims to improve fine motor skills and coordination | MAXO: occupational therapy (pqac-00000013) | Review therapeutic table (pqac-00000013) |
| Development | Speech therapy, with sign language and alternative/augmentative communication when needed | Useful for speech delay and communication impairment; review specifically recommends considering sign language and alternative communication devices | MAXO: speech therapy; augmentative and alternative communication support (pqac-00000013, pqac-00000011) | Review therapeutic table and phenotype summary (pqac-00000013, pqac-00000011) |
| Development/Behavior | Applied behavioral analysis (ABA) therapy if ASD is diagnosed | Consider when autism spectrum disorder or autistic traits are clinically confirmed | MAXO: behavioral therapy / applied behavior analysis (pqac-00000013) | Review therapeutic table (pqac-00000013) |
| Hearing | Full hearing evaluation | Recommended every two years in the review; hearing impairment is less common but documented | Modality: audiology/hearing assessment, brainstem auditory pathway testing where indicated (pqac-00000013, pqac-00000011) | Review follow-up recommendations and phenotype summary (pqac-00000013, pqac-00000011) |
| Genetics | Diagnostic evaluation for BBSOAS in any person with ONH or OA plus developmental delay/ID | During infancy, suspicion may arise from hypotonia, feeding difficulties, epilepsy, and poor eye tracking, even before full phenotype is evident | MAXO: genetic counseling; genomic diagnostic evaluation (pqac-00000013) | Review diagnostic recommendation (pqac-00000013) |
| Genetics | Chromosomal microarray analysis (CMA) for deletions | Appropriate first-line genome-wide technology when copy-number loss of NR2F1 or nearby region is suspected | Modality: chromosome microarray analysis (CMA) (pqac-00000013, pqac-00000012) | Review discussing deletions and diagnostic technologies (pqac-00000013, pqac-00000012) |
| Genetics | Whole-exome sequencing (WES) or large next-generation sequencing panels for SNVs/indels | Most individuals are expected to be diagnosed using genome-wide sequencing technologies because no pathognomonic clinical feature exists | Modality: WES; multigene NGS panel; single-gene NR2F1 analysis where phenotype strongly suggests diagnosis (pqac-00000013, pqac-00000008) | Review diagnostic recommendation and case report identified by WES (pqac-00000013, pqac-00000008) |
| Genetics | Variant interpretation under ACMG/AMP framework | Important because missense variants, especially in the DNA-binding domain, may require structured interpretation and can correlate with severity | MAXO: clinical molecular diagnosis; framework: ACMG/AMP variant classification (pqac-00000002, pqac-00000003) | 2025 case report and literature summary citing ACMG/AMP use and genotype-phenotype observations (pqac-00000002, pqac-00000003) |
| Multidisciplinary follow-up | Coordinated ophthalmology, neurology, developmental pediatrics/rehabilitation, audiology, and genetics follow-up | Real-world care is supportive and longitudinal; no approved disease-modifying therapy currently exists | MAXO: multidisciplinary care management (pqac-00000013, pqac-00000002) | Review recommendations and recent case report noting symptomatic management only (pqac-00000013, pqac-00000002) |


*Table: This table summarizes currently supported diagnostic evaluations and supportive management strategies for Bosch–Boonstra–Schaaf optic atrophy syndrome across vision, neurology, development, hearing, and genetics. It is useful for translating the literature into a practical, ontology-ready care framework for a disease knowledge base.*