| Domain | Finding / statistic | Ontology suggestions | Evidence type / source |
|---|---|---|---|
| Disease identity | Brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS); OMIM 618476; Open Targets disease entity also indexed as EFO_0010268 | MONDO: not confirmed from available sources; EFO_0010268; MeSH/Orphanet: not confirmed from available sources | Aggregated disease-level resources and literature synthesis (pqac-00000014, pqac-00000016, pqac-00000011) |
| Synonyms / disease framing | Pediatric-onset CSF1R-related disorder; autosomal-recessive CSF1R disorder; part of the CSF1R-related disorder continuum, distinct from dominant CSF1R-ALSP | NCIT: disease concept not confirmed; related concept suggestion: leukodystrophy / osteosclerosis terms as applicable | Review and systematic review (pqac-00000014, pqac-00000011) |
| Causal gene / inheritance | Biallelic CSF1R pathogenic variants; autosomal recessive inheritance; 17/19 homozygous and 2/19 compound heterozygous reported cases | HGNC gene: **CSF1R**; GO-linked process suggestions: microglia development, osteoclast differentiation | Human clinical genetics/systematic review (pqac-00000002, pqac-00000011, pqac-00000012) |
| Variant spectrum | 11 distinct CSF1R variants in 19 patients: splice (n=3), missense (n=3), nonsense (n=2), intronic (n=2), in-frame deletion (n=1); all disrupted the tyrosine kinase domain or led to nonsense-mediated decay | Sequence ontology suggestions: missense_variant, splice_donor/acceptor_variant, stop_gained, intron_variant, inframe_deletion | Systematic review of reported patients (pqac-00000001, pqac-00000004, pqac-00000011) |
| Onset / course | First symptoms: perinatal n=5, infancy n=2, childhood n=5, adulthood n=1; severe, usually progressive neurodevelopmental/neurodegenerative course | HPO: HP:0003577 Congenital onset; HP:0003593 Infantile onset; HP:0012758 Neurodevelopmental abnormality; HP:0002063 Rigidity | Systematic review/natural history synthesis (pqac-00000001, pqac-00000014, pqac-00000015) |
| Neurologic phenotype frequency | Speech disturbance 13/15; cognitive decline 12/14; spasticity/rigidity 12/15; hyperreflexia 11/14; pathologic reflexes 8/11; seizures 9/16; dysphagia 9/12; developmental delay 7/14; infantile hypotonia 3/11; optic nerve atrophy 2/7 | HPO suggestions: HP:0002463 Language developmental delay / speech disturbance; HP:0001263 Global developmental delay; HP:0001250 Seizure; HP:0001257 Spasticity; HP:0001347 Hyperreflexia; HP:0002015 Dysphagia; HP:0001252 Hypotonia; HP:0000648 Optic atrophy | Human case aggregation (pqac-00000001, pqac-00000002, pqac-00000003) |
| Skeletal phenotype frequency | Skeletal deformities in 13/17; phenotype described within the dysosteosclerosis–Pyle disease spectrum | HPO suggestions: HP:0000925 Abnormality of the vertebral column; HP:0000938 Osteosclerosis; HP:0010669 Metaphyseal widening; UBERON: skeleton | Human case aggregation/review (pqac-00000001, pqac-00000002) |
| Neuroimaging frequency | White-matter changes 19/19; calcifications 15/18; agenesis/abnormality of corpus callosum 12/16; ventriculomegaly 13/19; Dandy-Walker complex 7/19; cortical abnormalities 4/10 | HPO suggestions: HP:0007256 Agenesis of corpus callosum; HP:0002119 Ventriculomegaly; HP:0001272 Cerebral calcification; HP:0002500 Abnormal cerebral white matter morphology; UBERON: corpus callosum, cerebral white matter, cerebellum | Human imaging synthesis (pqac-00000001, pqac-00000002, pqac-00000005, pqac-00000015) |
| Pathology | Single autopsy showed absence of corpus callosum, absence of microglia, severe white-matter atrophy with axonal spheroids, gliosis, and numerous dystrophic calcifications | CL suggestion: microglial cell; GO/CC: myelin sheath, axon; HPO: HP:0002500 Abnormal cerebral white matter morphology | Human neuropathology (pqac-00000001, pqac-00000004, pqac-00000011) |
| Mortality / prognosis | At least 6 reported deaths among 19 compiled cases: 3 in infancy, 2 in childhood, 1 at unspecified age; prognosis generally poor with high early-life morbidity and mortality | HPO suggestion: HP:0003819 Childhood death / mortality-related annotation as local schema permits | Human case aggregation (pqac-00000001, pqac-00000002) |
| Core mechanism | Loss of CSF1R signaling impairs mononuclear-phagocyte lineage development, especially microglia and osteoclasts, linking congenital brain malformation/white-matter degeneration with dysosteosclerosis | GO suggestions: microglia development, osteoclast differentiation, receptor tyrosine kinase signaling, myeloid cell differentiation; CL: microglial cell, osteoclast | Human + model-organism convergence (pqac-00000010, pqac-00000014, pqac-00000008) |
| Cellular / tissue mechanism | Upstream: CSF1R kinase-domain dysfunction or NMD; intermediate: deficient microglia and osteoclast development/function; downstream: white-matter degeneration, calcifications, ventriculomegaly/brain malformations, osteosclerosis | GO suggestions: colony-stimulating factor receptor signaling pathway, CNS development, bone resorption; UBERON: brain, cerebral white matter, bone | Mechanistic interpretation from human pathology and models (pqac-00000009, pqac-00000010, pqac-00000014) |
| Diagnosis | Diagnosis relies on clinical phenotype plus neuroimaging and confirmation of biallelic CSF1R variants by sequencing; reported methods include targeted NGS/panel testing and prenatal CVS-based family testing in one family | HPO panel terms above; LOINC/SNOMED not confirmed from available sources | Human case report and review (pqac-00000006, pqac-00000000, pqac-00000011) |
| Differential diagnosis | Should be distinguished from dominant CSF1R-ALSP and from other genetic dysosteosclerosis/osteopetrosis entities such as **SLC29A3**-related dysosteosclerosis and **TNFRSF11A**-related osteoclast-poor dysosteosclerosis | Suggested disease neighbors for curation: CSF1R-related leukoencephalopathy, dysosteosclerosis, osteopetrosis | Expert review/systematic review (pqac-00000011, pqac-00000014) |
| Recent developments (2023–2024) | 2023 systematic review expanded the cohort to 19 patients and formalized overlap with CSF1R-ALSP; 2024 translational work in CSF1R disorders advanced microglia disease modeling and microglia-replacement concepts, but not BANDDOS-specific therapy | GO/CL suggestions as above | Recent review and translational studies (pqac-00000001, pqac-00000008) |
| Treatment status | No BANDDOS-specific approved disease-modifying therapy identified. Management is supportive. Authors propose a potential “window of opportunity” to adapt therapies used in CSF1R-ALSP, especially HSCT, but direct BANDDOS efficacy data are lacking; no relevant BANDDOS interventional trial was identified in the retrieved evidence | NCIT suggestions: Supportive care; Hematopoietic Stem Cell Transplantation (as extrapolative/experimental concept) | Expert opinion/systematic review plus related-disease treatment literature (pqac-00000001, pqac-00000012) |
| Evidence base caveat | Evidence is derived from individual case reports/series aggregated into disease-level review; denominators vary by phenotype because not all features were reported in every patient | Evidence code suggestion: human clinical case report, systematic review, model organism | Methodological note from systematic review (pqac-00000001, pqac-00000002) |


*Table: This table condenses the most actionable disease-characteristic evidence for BANDDOS, emphasizing reported denominators, mechanistic interpretation, and current treatment limitations. It is useful as a compact knowledge-base population aid anchored to the available human and translational evidence.*