| domain | key item | suggested ontology term/identifier | evidence/interpretation |
|---|---|---|---|
| disease | Congenital hydrocephalus | MONDO:0016349 | Congenital/pediatric hydrocephalus entity used in Open Targets; defined as abnormal CSF accumulation beginning prenatally or at birth, with major genetic and structural heterogeneity (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000015) |
| phenotype | Hydrocephalus | HPO: HP:0000238 | Core phenotype; excess CSF with ventricular enlargement and potential elevated intracranial pressure (pqac-00000001, pqac-00000002) |
| phenotype | Ventriculomegaly | HPO: HP:0002119 | Common imaging phenotype in fetal/neonatal diagnosis; often detected prenatally by ultrasound/MRI (pqac-00000001, pqac-00000002) |
| phenotype | Macrocephaly | HPO: HP:0000256 | Common clinical manifestation in infant hydrocephalus; head circumference monitoring is standard clinical follow-up (pqac-00000006, pqac-00000031) |
| phenotype | Bulging fontanelle | HPO: HP:0000239 | Practical bedside sign of raised intracranial pressure in infants; relevant to hydrocephalus monitoring (pqac-00000006, pqac-00000031) |
| phenotype | Increased intracranial pressure | HPO: HP:0002516 | Downstream physiologic consequence of ventricular enlargement; a major treatment target and monitoring endpoint (pqac-00000002, pqac-00000030, pqac-00000033) |
| phenotype | Aqueductal stenosis | HPO: HP:0002625 | Major obstructive mechanism; especially associated with L1CAM-related/X-linked forms and non-syndromic CH (pqac-00000011, pqac-00000012) |
| phenotype | Developmental delay | HPO: HP:0001263 | Frequent long-term neurodevelopmental outcome in pediatric hydrocephalus cohorts (pqac-00000019) |
| phenotype | Intellectual disability | HPO: HP:0001249 | Reported in monogenic forms including L1 syndrome; severity variable (pqac-00000003, pqac-00000012) |
| phenotype | Seizures | HPO: HP:0001250 | Important neurologic comorbidity/morbidity in pediatric hydrocephalus (pqac-00000019) |
| phenotype | Spasticity / gait abnormality | HPO: HP:0001257; HP:0001288 | Motor impairment and gait difficulty are recognized morbidity features in affected children (pqac-00000019) |
| phenotype | Corpus callosum abnormalities | HPO: HP:0001273 | Corpus callosum malformations are prominent in some genetic cases, particularly L1CAM-related disease (pqac-00000003) |
| anatomy | Brain ventricular system | UBERON: brain ventricular system (verify exact ID in target ontology) | Primary anatomic compartment enlarged in disease (pqac-00000002) |
| anatomy | Lateral ventricle | UBERON: lateral ventricle (verify exact ID in target ontology) | Frequently measured on prenatal/postnatal imaging and targeted in shunt catheter placement (pqac-00000002, pqac-00000032) |
| anatomy | Third ventricle | UBERON: third ventricle (verify exact ID in target ontology) | Relevant to obstructive hydrocephalus and ETV procedure (pqac-00000002, pqac-00000016) |
| anatomy | Fourth ventricle | UBERON: fourth ventricle (verify exact ID in target ontology) | Included in ventricular system anatomy affected by CSF flow abnormalities (pqac-00000002) |
| anatomy | Cerebral aqueduct | UBERON: cerebral aqueduct (verify exact ID in target ontology) | Critical site for aqueductal stenosis/obstruction (pqac-00000011, pqac-00000012) |
| anatomy | Choroid plexus | UBERON: choroid plexus (verify exact ID in target ontology) | Major CSF-producing tissue; implicated in secretion, barrier, and surgical cauterization strategies (pqac-00000015, pqac-00000030, pqac-00000032) |
| anatomy | Ependyma | UBERON: ependyma (verify exact ID in target ontology) | Ventricular lining central to ciliary motility and barrier/junction defects (pqac-00000002, pqac-00000011) |
| anatomy | Cerebral cortex | UBERON: cerebral cortex (verify exact ID in target ontology) | Affected secondarily by compression and developmentally in some genetic forms (pqac-00000002, pqac-00000008) |
| anatomy | Corpus callosum | UBERON: corpus callosum (verify exact ID in target ontology) | Malformation documented in monogenic disease presentations (pqac-00000003) |
| cell type | Ependymal cell | CL: ependymal cell (verify exact ID in target ontology) | Key motile-cilia-bearing cell type regulating CSF movement; repeatedly implicated in CH (pqac-00000002, pqac-00000011, pqac-00000014) |
| cell type | Choroid plexus epithelial cell | CL: choroid plexus epithelial cell (verify exact ID in target ontology) | Core CSF-secretory/barrier cell; transporter dysregulation implicated mechanistically (pqac-00000002, pqac-00000013, pqac-00000030) |
| cell type | Neural stem/progenitor cell | CL: neural stem cell / neural progenitor cell (verify exact ID in target ontology) | Junctional and neurogenic defects in ventricular zone progenitors linked to aqueductal and cortical abnormalities (pqac-00000008, pqac-00000011) |
| cell type | Neuron | CL: neuron (verify exact ID in target ontology) | Downstream injury/developmental disruption contributes to cognitive and motor phenotypes (pqac-00000003, pqac-00000008) |
| cell type | Astrocyte | CL: astrocyte (verify exact ID in target ontology) | Glial activation reported in animal mechanistic cascades downstream of obstruction (pqac-00000012) |
| cell type | Microglia | CL: microglial cell (verify exact ID in target ontology) | Inflammatory signaling is increasingly implicated in hydrocephalus pathobiology (pqac-00000009) |
| mechanism | Cilium movement | GO:0003341 | Strongest recurring upstream mechanism; motile cilia defects impair CSF propulsion (pqac-00000011, pqac-00000014, pqac-00000015) |
| mechanism | CSF circulation | GO: cerebrospinal fluid circulation (verify exact ID in target ontology) | Central disease process linking cilia, obstruction, and transporter dysfunction to ventricular dilation (pqac-00000002, pqac-00000015) |
| mechanism | Ion transport | GO:0006811 | Choroid plexus ion transporters regulate CSF secretion; NKCC-related dysregulation highlighted in models (pqac-00000002, pqac-00000013, pqac-00000015) |
| mechanism | Cell-cell junction organization | GO:0045216 | Apical/junctional defects in ventricular zone and ependyma contribute to aqueductal stenosis and barrier dysfunction (pqac-00000008, pqac-00000011) |
| mechanism | Neurogenesis | GO:0022008 | Developmental pathway implicated through TRIM71, SMARCC1 and other neurodevelopmental genes (pqac-00000008, pqac-00000011) |
| mechanism | Inflammatory response | GO:0006954 | Neuroinflammatory signaling is a recognized contributor/modifier in hydrocephalus biology (pqac-00000009) |
| mechanism | Apoptosis | GO:0006915 | Included among proposed molecular pathways contributing to tissue injury and ventricular pathology (pqac-00000015) |
| gene / inheritance | L1CAM | HGNC: L1CAM; X-linked inheritance | Established CH gene; classic X-linked aqueductal stenosis/L1 syndrome; accounts for a notable fraction of congenital cases (pqac-00000011, pqac-00000012, pqac-00000000) |
| gene / inheritance | AP1S2 | HGNC: AP1S2; X-linked inheritance | Established X-linked CH-associated gene with vesicle trafficking role (pqac-00000011, pqac-00000012, pqac-00000015) |
| gene / inheritance | MPDZ | HGNC: MPDZ; autosomal recessive inheritance | Established recessive CH gene; linked to planar polarity/junctional integrity and aqueduct/ependymal pathology (pqac-00000011, pqac-00000012, pqac-00000000) |
| gene / inheritance | CCDC88C | HGNC: CCDC88C; autosomal recessive inheritance | Established recessive CH gene; associated with cilia orientation/CSF flow abnormalities (pqac-00000011, pqac-00000012, pqac-00000000) |
| gene / inheritance | FOXJ1 | HGNC: FOXJ1; expanded evidence / candidate dominant mechanism | Strong mechanistic/candidate evidence for communicating hydrocephalus through impaired ependymal differentiation/ciliogenesis (pqac-00000011, pqac-00000009) |
| gene / inheritance | SMARCC1 | HGNC: SMARCC1; expanded evidence / autosomal dominant with incomplete penetrance reported | Increasing evidence linking chromatin remodeling and neural progenitor defects to CH (pqac-00000010, pqac-00000011, pqac-00000009) |
| gene / inheritance | TRIM71 | HGNC: TRIM71; expanded evidence / candidate | Neurodevelopmental candidate implicated in communicating CH and neural progenitor biology (pqac-00000011, pqac-00000000) |
| intervention | Ventriculoperitoneal shunt | NCIT-style: Ventriculoperitoneal Shunt Procedure (verify in NCIT) | Global standard surgical treatment; failure/revision remains common (pqac-00000001, pqac-00000018, pqac-00000032) |
| intervention | Endoscopic third ventriculostomy | NCIT-style: Endoscopic Third Ventriculostomy (verify in NCIT) | Standard option for selected obstructive cases; can avoid shunt dependence in some infants (pqac-00000002, pqac-00000016, pqac-00000018) |
| intervention | Choroid plexus cauterization | NCIT-style: Choroid Plexus Cauterization (verify in NCIT) | Used with ETV in infant hydrocephalus; long-term shunt freedom reported in selected cohorts (pqac-00000016, pqac-00000018) |
| intervention | Physical therapy | NCIT-style: Physical Therapy (verify in NCIT) | Supportive rehabilitation for motor impairment/spasticity/gait dysfunction; ontology-ready supportive care term (pqac-00000019) |
| intervention | Occupational therapy | NCIT-style: Occupational Therapy (verify in NCIT) | Supportive rehabilitation for developmental and functional deficits; commonly relevant in pediatric neurodisability (pqac-00000019) |
| intervention | Speech therapy | NCIT-style: Speech Therapy (verify in NCIT) | Supportive rehabilitation for neurodevelopmental sequelae when language/communication are affected (pqac-00000019) |


*Table: This compact ontology-ready table maps congenital hydrocephalus to suggested disease, phenotype, anatomy, cell type, mechanism, gene, and intervention terms. It is designed to support knowledge-base curation while flagging ontology IDs that should be verified in the target terminology.*