| domain | entity/phenotype/mechanism/anatomy/intervention | suggested ontology term and ID | evidence/qualification |
|---|---|---|---|
| disease | Juvenile Huntington disease (Westphal variant) | MONDO:0016621 juvenile Huntington disease | MONDO/OpenTargets association with HTT; juvenile form defined by onset before age 20-21 years in cohort literature; Westphal phenotype emphasizes rigidity/bradykinesia over chorea (pqac-00000000, pqac-00000019, pqac-00000020) |
| phenotype | Juvenile onset | HPO: Childhood onset — ID verification required | JOHD defined as symptom onset before age 21 years in Kids-JOHD and before/at 20 years in Swedish registry; use age-at-onset qualifier in phenotype annotations (pqac-00000019, pqac-00000020) |
| phenotype | Rigidity | HP:0002063 Rigidity | More severe in JoHD/Westphal phenotype than typical adult choreic presentation (pqac-00000020) |
| phenotype | Bradykinesia | HP:0002067 Bradykinesia | Registry/review context indicates bradykinesia is prominent in JoHD (pqac-00000020) |
| phenotype | Dystonia | HP:0001332 Dystonia | More severe in JoHD than in typical adult-onset HD (pqac-00000020) |
| phenotype | Seizures/epilepsy | HP:0001250 Seizure | Higher incidence of epilepsy in JoHD; epileptic seizures are much more frequent (pqac-00000020) |
| phenotype | Cognitive decline | HP:0001268 Mental deterioration | Cognitive changes are common and often early; longitudinal/registry data support cognitive burden (pqac-00000019, pqac-00000020) |
| phenotype | Behavioral abnormality | HP:0000708 Behavioral abnormality | Behavioral problems are part of core juvenile phenotype and may precede motor diagnosis (pqac-00000020, pqac-00000027) |
| phenotype | Dysarthria | HP:0001260 Dysarthria | Common progressive bulbar/motor manifestation in HD/JOHD; include as suggested term, juvenile-specific frequency not quantified here (pqac-00000027) |
| phenotype | Dysphagia | HP:0002015 Dysphagia | Relevant progressive swallowing complication in manifest HD; juvenile-specific frequency not quantified here (pqac-00000027) |
| phenotype | Gait abnormality | HP:0001288 Gait disturbance | Expected with progressive parkinsonism/rigidity and motor decline; longitudinal motor worsening supports relevance (pqac-00000019, pqac-00000027) |
| phenotype | Chorea (less prominent) | HP:0002072 Chorea | Chorea can occur but is less prominent in Westphal/juvenile phenotype than rigidity-bradykinesia-dystonia (pqac-00000020) |
| phenotype | Weight loss | HP:0001824 Weight loss | Clinically relevant in HD and addressed in symptomatic management guidance; juvenile-specific frequency not quantified here (pqac-00000025, pqac-00000027) |
| mechanism | Mutant huntingtin protein aggregation | GO:0097352 protein aggregation | Pathogenic HTT exon 1/polyQ protein is aggregation-prone; human and model evidence (pqac-00000016, pqac-00000027) |
| mechanism | Somatic CAG expansion / DNA mismatch repair | GO:0006298 mismatch repair | Strong human genetic and experimental evidence implicates MSH3, MLH1, PMS1/2, MLH3, FAN1 in somatic repeat instability and onset modification; no single GO term for “somatic CAG expansion” confidently assigned here (pqac-00000015, pqac-00000017, pqac-00000018, pqac-00000024) |
| mechanism | Autophagy dysfunction | GO:0006914 autophagy | Impaired autophagy and benefit from autophagy induction reported in HD models/patient-derived systems (pqac-00000005, pqac-00000006) |
| mechanism | Mitochondrial dysfunction | GO:0005739 mitochondrion / GO:0042775 mitochondrial ATP synthesis coupled electron transport | Human and model data support altered ATP production, respiratory chain defects, and pediatric hypometabolic signatures; process ID should be chosen per curation use case (pqac-00000005, pqac-00000006, pqac-00000021) |
| mechanism | Transcriptional dysregulation | GO:0006351 transcription, DNA-templated | mHTT disrupts transcriptional regulation in human brain and models (pqac-00000006, pqac-00000027) |
| mechanism | Neuroinflammation | GO:0050729 positive regulation of inflammatory response | Elevated inflammatory proteins/microglial markers in HD; pediatric specificity not established but disease-relevant (pqac-00000011) |
| mechanism | Synaptic signaling dysfunction | GO:0099536 synaptic signaling | Synaptic dysfunction/excitotoxic signaling are established HD mechanisms (pqac-00000006, pqac-00000027) |
| cell type | Striatal medium spiny neuron | CL term and ID verification required | Human postmortem study directly implicates MSNs as major site of somatic expansion and vulnerability (pqac-00000018) |
| cell type | Cholinergic interneuron | CL term and ID verification required | Human postmortem study found large mHTT CAG expansions in striatal cholinergic interneurons despite relative sparing (pqac-00000018) |
| cell type | Purkinje cell | CL:0000121 Purkinje cell | Human postmortem study found expansions in cerebellar Purkinje neurons (pqac-00000018) |
| cell type | Astrocyte | CL:0000127 astrocyte | Glial/neuroinflammatory involvement widely reported; cell ontology term appropriate for annotation (pqac-00000011) |
| cell type | Microglia | CL:0000129 microglial cell | Microglial activation and inflammatory markers are documented in HD (pqac-00000011) |
| anatomy | Caudate nucleus | UBERON:0002420 caudate nucleus | Core vulnerable striatal structure in HD/JOHD (pqac-00000018, pqac-00000027) |
| anatomy | Putamen | UBERON:0001874 putamen | Core vulnerable striatal structure in HD/JOHD (pqac-00000018, pqac-00000027) |
| anatomy | Striatum | UBERON:0002435 striatum | Principal site of atrophy and biomarker change; annualized striatal volume loss in JOHD reported (pqac-00000019, pqac-00000027) |
| anatomy | Cerebral cortex | UBERON:0000956 cerebral cortex | Cortical involvement, transcriptional changes, and pediatric frontal cortical GLUT defects reported (pqac-00000021, pqac-00000027) |
| anatomy | Cerebellum | UBERON:0002037 cerebellum | Purkinje-cell somatic expansion documented; region less classically affected than striatum (pqac-00000018) |
| cellular component | Nucleus | GO:0005634 nucleus | Nuclear inclusions/aggregation and transcriptional effects are central features (pqac-00000016, pqac-00000027) |
| cellular component | Mitochondrion | GO:0005739 mitochondrion | Mitochondrial defects and altered energy metabolism are repeatedly implicated (pqac-00000005, pqac-00000021) |
| cellular component | Autophagosome | GO:0005776 autophagosome | Suitable component term for autophagy pathway annotation (pqac-00000005, pqac-00000006) |
| cellular component | Proteasome | GO:0000502 proteasome complex | UPS/proteasomal dysfunction is implicated in HD pathobiology (pqac-00000006) |
| intervention | Genetic testing | NCIT:C15709 Genetic Testing | Molecular confirmation by HTT CAG sizing is diagnostic cornerstone (pqac-00000023, pqac-00000026) |
| intervention | Brain MRI | NCIT:C16809 Magnetic Resonance Imaging | Structural MRI used for progression assessment; striatal volume is a candidate JOHD biomarker (pqac-00000013, pqac-00000019) |
| intervention | Physical therapy | NCIT term ID verification required | Recommended supportive multidisciplinary care in HD guidelines; exact NCIT concept should be confirmed during implementation (pqac-00000025, pqac-00000027) |
| intervention | Occupational therapy | NCIT term ID verification required | Part of supportive multidisciplinary management (pqac-00000020, pqac-00000027) |
| intervention | Speech therapy | NCIT term ID verification required | Relevant for dysarthria/dysphagia support; exact NCIT ID should be confirmed (pqac-00000027) |
| intervention | Antisense oligonucleotide therapy | NCIT:C129670 Antisense Oligonucleotide Therapy | Disease-modifying strategy under investigation for HTT lowering; not approved for JOHD (pqac-00000007, pqac-00000024) |
| intervention | RNA interference | NCIT:C18250 RNA Interference | Preclinical/therapeutic HTT-lowering strategy and MSH3-targeting silencing approach (pqac-00000022, pqac-00000024) |
| intervention | Genetic counseling | NCIT:C15214 Genetic Counseling | Essential for predictive testing, family planning, and juvenile/family cases (pqac-00000026, pqac-00000027) |


*Table: This table provides a compact ontology-oriented mapping for juvenile Huntington disease (Westphal variant), linking disease concepts, phenotypes, mechanisms, cell types, anatomy, and interventions to suggested ontology terms and IDs. It is designed to support structured knowledge-base curation while clearly flagging terms that require ID verification.*