| domain | high-confidence finding | quantitative data/example | ontology suggestions |
|---|---|---|---|
| Definition / IDs | Cerebral palsy (CP) is a group of permanent disorders of movement and posture due to a non-progressive disturbance/lesion of the developing fetal or infant brain; disease-level knowledge here is derived primarily from aggregated reviews, registries, and cohort studies rather than individual EHR alone. MONDO for cerebral palsy is available. (pqac-00000001, pqac-00000017, pqac-00000000) | MONDO: `MONDO:0006497`; MeSH term present in ClinicalTrials browse: `D002547 Cerebral Palsy`. | MONDO:0006497; MeSH:D002547; HPO: HP:0100021 *Cerebral palsy* |
| Classification | Standard clinical subtype classification includes spastic, dyskinetic, ataxic, and hypotonic CP; function is commonly staged with GMFCS, MACS, CFCS, and EDACS. (pqac-00000006, pqac-00000014) | Slovenian pediatric cohort: spastic 85%, dyskinetic 13%, ataxic 2%. Functional systems: GMFCS I-V, MACS I-V. (pqac-00000003, pqac-00000014) | HPO: HP:0001257 *Spasticity*; HP:0001270 *Motor delay*; HP:0100022 *Dyskinetic cerebral palsy*; HP:0001251 *Ataxia* |
| Core phenotypes | CP is fundamentally a motor syndrome, often accompanied by cognitive, epilepsy, language, and mobility impairments; severity and participation limits vary widely. (pqac-00000001, pqac-00000006) | Approximate comorbidity frequencies from 2024 review: cognitive impairment ~50%, epilepsy ~33%, language impairment ~33%, ~40% unable to walk independently. (pqac-00000001) | HPO: HP:0001257 *Spasticity*; HP:0001263 *Developmental regression* not typical; HP:0001249 *Intellectual disability*; HP:0001250 *Seizure*; HP:0000750 *Delayed speech and language development* |
| Epidemiology | CP remains the most common childhood physical disability, with lower rates in many high-income settings than historically, but higher burden in low-/middle-income settings. (pqac-00000001, pqac-00000002, pqac-00000016) | Prevalence estimates: ~1.4-1.6 per 1,000 live births in some high-income settings; ~3.3-3.4 per 1,000 in LMIC settings; global range 1.5 to >4 per 1,000. Preterm infants account for ~43% of cases. (pqac-00000001, pqac-00000002, pqac-00000016) | MONDO:0006497; NCIT:C7639 *Preterm Birth*; HPO: HP:0001622 *Premature birth* |
| Etiology / risk factors | CP is etiologically heterogeneous: prematurity/low birth weight, low Apgar, intrauterine infection, congenital brain malformations, PROM, placental abruption, maternal disease, neonatal hyperbilirubinemia, stroke, and hypoxic-ischemic injury all contribute. (pqac-00000016, pqac-00000015, pqac-00000006) | Systematic review found 40 consistent determinants from 95 articles; 24 studies implicated prematurity/low weight and 15 implicated low Apgar. HIE in term infants occurs in ~1.5/1,000 births and is a leading cause of CP. (pqac-00000016, pqac-00000015) | HPO: HP:0001518 *Small for gestational age*; HP:0003819 *Abnormality of the placenta*; UBERON: placenta / brain; GO: GO:0006954 *inflammatory response* |
| Protective / preventive factors | Established prevention is mainly perinatal/neonatal: antenatal magnesium sulfate, antenatal corticosteroids, prophylactic caffeine in preterm infants, and therapeutic hypothermia for moderate-severe HIE. These are established care, not experimental. (pqac-00000002, pqac-00000012, pqac-00000014) | Reported effect sizes/examples: magnesium sulfate prevents ~30% of CP in very preterm infants; therapeutic hypothermia prevents ~15% of hypoxia-associated cases when used within 6 hours. (pqac-00000002, pqac-00000014) | NCIT: magnesium sulfate, corticosteroid, caffeine, hypothermia; CHEBI: magnesium sulfate, caffeine |
| Genetic architecture | CP includes a substantial monogenic/CNV component and should not be treated as exclusively acquired. Recurrent genes/pathways converge on thrombosis, angiogenesis, mitochondrial/oxidative phosphorylation, neuronal migration, and autophagy, with overlap with broader neurodevelopmental disorders. (pqac-00000001, pqac-00000017) | Meta-analytic estimates cited in 2024 review: SNV molecular diagnostic yield ~23%, CNV yield ~5%. >100 recurrent genes discussed. (pqac-00000017) | HGNC gene examples: ATL1, CTNNB1, SPAST, PROC, COL4A1, L1CAM, KIF1A; GO: neuronal migration, oxidative phosphorylation, autophagy |
| 2024 genomics development | Trio whole-genome sequencing has now provided large-scale direct evidence for CP genomic architecture. This is a key recent development. (pqac-00000009, pqac-00000010, pqac-00000011) | Nature Genetics 2024 cohort: 327 trios; pathogenic/likely pathogenic variants in 37/327 (11%), VUS in 58/327 (18%), no clinically relevant variant in 232/327 (71%); P/LP group had more cognitive impairment (49%) and brain maldevelopments (11%). (pqac-00000010, pqac-00000011) | HGNC: MT-TQ, MT-TS1, MT-ND5; GO: GO:0005739 *mitochondrion*; HPO: HP:0001250 *Seizure*; HP:0001249 *Intellectual disability* |
| Example implicated genes | Multiple cohorts identified plausible/definite CP-related variants, supporting clinical heterogeneity and genetic testing. (pqac-00000003, pqac-00000007) | Slovenian cohort: 9/136 (6.6%) with ATL1, CTNNB1, DYRK1, KMT2A, PROC, SPAST, ZC4H2, ZSWIM6; 2026 integrative genomic cohort found P/LP variants in 24/66 (36.4%) with genes including SPAST, KIF1A, PLA2G6, CTNNB1, L1CAM, SYNGAP1. (pqac-00000003, pqac-00000007) | HGNC: ATL1, CTNNB1, SPAST, KIF1A, PLA2G6, L1CAM, SYNGAP1 |
| MRI / anatomy | Brain MRI is abnormal in most children with CP and helps classify etiology/anatomy; white matter injury is the most frequent MRI pattern, but normal MRI does not exclude CP or genetic causes. (pqac-00000017, pqac-00000003) | MRI categories (SCPE framework): maldevelopments, predominant white matter injury, predominant gray matter injury, miscellaneous abnormalities, normal. In one cited study: maldevelopments ~11%, white matter injury 49%, gray matter injury 21%; MRI abnormal in >80% overall. Normal MRI occurred in 42% of spastic diplegic CP in one series; 3/9 genetically solved Slovenian cases had normal MRI. (pqac-00000017, pqac-00000003) | UBERON: brain, cerebral white matter, cerebral cortex, basal ganglion, thalamus, cerebellum; HPO: HP:0002500 *Abnormal cerebral white matter morphology* |
| Pathophysiology / mechanism | A common mechanistic chain in acquired CP is prenatal/perinatal hypoxia-ischemia ± inflammation: reduced oxygen/blood flow causes primary energy failure, ATP depletion, lactate accumulation, ion pump failure, calcium overload, oxidative stress, necrosis/apoptosis, then secondary inflammatory injury affecting selective neurons and oligodendrocyte-lineage cells. (pqac-00000015, pqac-00000018) | HIE severe mortality cited at 25-50%; one-third to one-half of cooled survivors still had persistent neurologic abnormalities or low IQ at 6-7 years in large-animal review discussion. White matter injury and progenitor oligodendrocyte vulnerability are emphasized in fetal sheep and piglet models. (pqac-00000015, pqac-00000018) | GO: GO:0006091 *generation of precursor metabolites and energy*; GO:0006979 *response to oxidative stress*; GO:0006954 *inflammatory response*; CL: oligodendrocyte precursor cell, microglial cell, neuron |
| Diagnosis | Early diagnosis is increasingly feasible using clinical neurodevelopmental tools plus MRI; at-risk infants can often be identified far earlier than the historic 2-year diagnosis window. (pqac-00000012, pqac-00000017) | Hammersmith Infant Neurological Examination + brain MRI allows reliable diagnosis in at-risk infants at ~5 months corrected age; reviews note prediction by 6-12 months and sometimes as early as 3 months corrected age with GMA/HINE/MRI. (pqac-00000012, pqac-00000017) | NCIT: Magnetic Resonance Imaging; HPO: abnormal general movements; clinical tools: GMA, HINE, GMFCS |
| Differential / genomic workflow | Genetic evaluation is especially warranted when imaging/history are atypical or insufficient, including normal MRI, no clear perinatal insult, severe phenotype, family history, or CP-like/progressive presentations. This is increasingly recommended clinical workflow rather than purely research. (pqac-00000003, pqac-00000017) | 2024 review: SNV yield ~23% and CNV yield ~5%; Slovenian cohort identified cases despite normal MRI or unremarkable history. Advanced genomic review argues for WES/WGS and other state-of-the-art genomic approaches to improve diagnosis. (pqac-00000017, pqac-00000003) | NCIT: Whole Exome Sequencing, Whole Genome Sequencing, Chromosomal Microarray Analysis |
| Established treatment: rehabilitation | Best-supported rehabilitation is early, active, task-specific, and goal-directed; technology can augment but not replace motor learning. NDT-Bobath is not superior to usual care. (pqac-00000008, pqac-00000012, pqac-00000013) | Traffic-light review covered 182 interventions and 398 outcomes; effective allied health examples include CIMT, bimanual training, treadmill/partial body-weight support training, strength training, goal-directed training, and home programs. (pqac-00000002, pqac-00000008) | NCIT: Physical Therapy, Occupational Therapy, Constraint-Induced Movement Therapy, Treadmill Training |
| Established treatment: pharmacologic / surgical | Established management for selected impairments includes botulinum toxin, intrathecal baclofen, selective dorsal rhizotomy, hip surveillance, scoliosis correction, and anticonvulsants, typically combined with rehabilitation. (pqac-00000008, pqac-00000013) | Strong-evidence examples from systematic review: botulinum toxin, intrathecal baclofen, selective dorsal rhizotomy, anti-convulsants, dentistry, hip surveillance, scoliosis correction. (pqac-00000008) | NCIT: Botulinum Toxin, Baclofen, Selective Dorsal Rhizotomy, Hip Surveillance, Scoliosis Surgery |
| Unsupported / low-evidence care | Some commonly promoted interventions lack convincing benefit and should be distinguished from evidence-based care. (pqac-00000013) | Examples flagged as lacking evidence in rehabilitation review: hyperbaric oxygen therapy, craniosacral manipulation, unstructured sensory integration, passive stretching without task-specific goals. (pqac-00000013) | NCIT: Hyperbaric Oxygen Therapy; supportive note: low-evidence / not established |
| Prognosis | The brain lesion is non-progressive, but disability is lifelong and functional trajectories vary by subtype, GMFCS level, comorbidity burden, and response to therapy. Prognosis is influenced by prematurity, HIE severity, cognition, and associated impairments. (pqac-00000001, pqac-00000012, pqac-00000015) | Severe HIE mortality 25-50%; in a cohort of infants <25 weeks, males were more likely to develop CP and impaired cognition than females. Quality-of-life burden is substantial but precise modern disease-wide mortality/life expectancy estimates were not retrieved in this conversation. (pqac-00000015) | HPO: HP:0001263 *Global developmental delay*; HP:0001249 *Intellectual disability*; ICF/GMFCS useful for prognosis |
| Current experimental / real-world trials | Ongoing interventional work includes neuromodulation, robotic exoskeleton gait therapy, biomarker-linked gait therapy, and stem-cell/conditioned-medium studies. These are experimental, not standard of care. (pqac-00000019, pqac-00000020, pqac-00000021, pqac-00000022) | Examples: NCT06586437 neuromodulation of cortex/spinal cord, randomized, double-masked, n=50; NCT05158218 robotic exoskeleton gait training vs physical therapy, randomized, n=64; NCT04360395 gait therapy with neurophysiology responder analysis, n=120; NCT04314687 allogeneic umbilical cord MSCs ± conditioned medium vs standard therapy, phase 1/2, n=78. (pqac-00000019, pqac-00000020, pqac-00000021, pqac-00000022) | NCIT: Transcutaneous Current Stimulation, Robotic Exoskeleton, Gait Therapy, Mesenchymal Stem Cell Therapy |
| Animal / translational models | CP has no single standard natural veterinary analogue; experimental models focus on hypoxia-ischemia, inflammation, hemorrhage, and prematurity-related injury. Large animals improve clinical translatability; rodent models remain useful mechanistically. (pqac-00000015, pqac-00000018) | Large-animal examples: fetal sheep for progenitor oligodendrocyte vulnerability and white matter injury; newborn piglets for term HIE systems injury; non-human primates for cortical/basal ganglia/thalamic injury patterns; maternal immune activation is an important added risk-factor model. Hypothermia success in human neonates was informed by animal work. (pqac-00000015, pqac-00000018) | NCBI Taxon examples: Mus musculus, Rattus norvegicus, Ovis aries, Sus scrofa, Macaca mulatta; GO/CL: oligodendrocyte precursor, microglia, neuron |


*Table: This compact table summarizes high-confidence, evidence-backed facts for a cerebral palsy knowledge-base entry, spanning definition, phenotypes, epidemiology, genetics, diagnosis, treatment, prognosis, and models. It distinguishes established care from experimental approaches and includes ontology suggestions for structured annotation.*