| Domain | Curated value | Evidence type | Ontology/identifier suggestion |
|---|---|---|---|
| Disease name | Spinal and bulbar muscular atrophy (SBMA), also called Kennedy disease; older synonym: bulbospinal muscular atrophy (pqac-00000002, pqac-00000018) | Human clinical review; population-genomics primary study | MONDO:0016113; MeSH D055534 |
| Core disease identifiers | MONDO:0016113; OMIM 313200; ORPHA 481; MeSH D055534 “Bulbo-Spinal Atrophy, X-Linked” (pqac-00000015) | Curated disease/resource mapping in conversation; ClinicalTrials MeSH browse | MONDO:0016113; OMIM:313200; Orphanet:481; MeSH:D055534 |
| Etiologic gene | AR (androgen receptor), exon 1 CAG-repeat expansion on the X chromosome (pqac-00000002, pqac-00000018) | Human clinical review; population-genomics primary study | HGNC:644; NCBI Gene:367 |
| Pathogenic repeat threshold | Pathogenic alleles generally defined as \>=38 CAG repeats; conversation sources also note disease beyond 37 repeats and typical disease range about 39–72 repeats (pqac-00000018, pqac-00000001, pqac-00000008, pqac-00000013, pqac-00000015) | Population-genomics primary study; review; trial eligibility criteria | Repeat expansion testing; AR CAG repeat |
| Inheritance | X-linked recessive / X-linked adult-onset disorder; full phenotype primarily in males, with female carriers often asymptomatic or mildly affected (pqac-00000002, pqac-00000004) | Human clinical reviews | HP:0001419; NCIT:C85867 |
| Typical onset/course | Adult onset, commonly 30–50 years, slowly progressive; mean onset around early 40s reported in recent genomic study background (pqac-00000004, pqac-00000008, pqac-00000018) | Human clinical review; population-genomics primary study | HP:0003581; HP:0003677 |
| Major motor phenotype | Progressive proximal limb weakness and atrophy; ~70% first notice lower-limb weakness, and one review reports proximal weakness in 97% with lower-limb involvement in 86.7% (pqac-00000000, pqac-00000004) | Human clinical reviews | HP:0003323; HP:0003202 |
| Bulbar phenotype | Dysarthria and dysphagia are common and often later manifestations; dysphagia reported in ~80% in review literature (pqac-00000002, pqac-00000004, pqac-00000007) | Human clinical reviews/guideline | HP:0001260; HP:0002015 |
| Tremor/sensory phenotype | Postural hand tremor can predate weakness by >10 years; sensory abnormalities reported in many patients (72–100% in review summary) (pqac-00000000, pqac-00000007) | Human clinical reviews | HP:0001337; HP:0003401 |
| Endocrine/reproductive phenotype | Partial androgen insensitivity with gynecomastia, testicular atrophy, erectile dysfunction, reduced fertility (pqac-00000000, pqac-00000007, pqac-00000020) | Human clinical reviews; mechanistic primary study intro | HP:0000132; HP:0000047 |
| Metabolic phenotype | Glucose intolerance, hyperlipidemia/dyslipidemia, insulin resistance, fatty liver/metabolic syndrome are recognized extra-neurological features (pqac-00000002, pqac-00000007, pqac-00000018) | Human consensus guideline; population-genomics background | HP:0003074; HP:0003124 |
| Respiratory/cause of death | Overt respiratory failure is uncommon, but aspiration pneumonia and respiratory infections are major complications; respiratory infectious diseases account for >50% of deaths in one review summary (pqac-00000000, pqac-00000010) | Human clinical reviews | HP:0002093; HP:0006536 |
| Cardiac involvement | Cardiac repolarization abnormalities/Brugada-type ECG are recognized in some cohorts; trial protocols exclude affected patients (pqac-00000002, pqac-00000007, pqac-00000013, pqac-00000014) | Human consensus guideline; trial eligibility | HP:0011715 |
| Principal organs/tissues | Lower motor neuron system and skeletal muscle are primary sites; dorsal root ganglia/sensory system and extra-neurological tissues are also involved (pqac-00000000, pqac-00000007, pqac-00000017) | Human review; mouse mechanistic study | UBERON:0001017 spinal cord; UBERON:0001134 skeletal muscle |
| Principal cell types | Lower motor neurons and skeletal myofibers are central; evidence also implicates sensory neurons/dorsal root ganglion cells (pqac-00000000, pqac-00000007, pqac-00000019) | Human review; mouse/human tissue primary study | CL:0000100 motor neuron; CL:0000187 muscle cell |
| Core upstream mechanism | Ligand-dependent toxic gain of function of polyglutamine-expanded AR, especially androgen-dependent nuclear accumulation of mutant AR (pqac-00000000, pqac-00000001, pqac-00000020) | Human review; mechanistic primary study | GO:0005634 nucleus; GO:0006915 apoptotic process |
| Key downstream mechanisms | Transcriptional dysregulation, altered proteostasis/autophagy, mitochondrial dysfunction, metabolic shift, and Src pathway activation; phosphorylated Src is increased before onset in mouse spinal cord and muscle (pqac-00000002, pqac-00000005, pqac-00000019) | Human consensus review; mouse phosphoproteomic primary study | GO:0016567 protein ubiquitination; GO:0000422 autophagy; GO:0005739 mitochondrion; GO:0030971 receptor tyrosine kinase signaling |
| Muscle-driven disease component | Skeletal muscle is not only affected but can drive neuromuscular degeneration; muscle-specific excision of mutant AR rescued neuromuscular phenotypes in BAC fxAR121 mice (pqac-00000017, pqac-00000001) | Mouse primary study; review | GO:0006936 muscle contraction |
| Epidemiology: classical prevalence | Traditional prevalence estimates are about 1–2 per 100,000 or ~1:30,000 males, depending on study and population (pqac-00000000, pqac-00000018) | Human reviews; population-genomics background | Orphanet epidemiology field |
| Epidemiology: 2023 expansion frequency | 2023 whole-genome analysis estimated pathogenic AR expansion frequency at 1:3182 X chromosomes (95% CI 1:2309–1:4386) (pqac-00000018) | Human population-genomics primary study | AR CAG expansion frequency |
| Epidemiology: 2023 modeled prevalence | Using the new mutation frequency, modeled disease prevalence was 1:6887 males, suggesting underdiagnosis and/or reduced penetrance (pqac-00000018) | Human population-genomics primary study | SBMA prevalence estimate |
| Population structure/founder effects | Founder effects have been noted in Japanese, Finnish, and Italian populations in review literature (pqac-00000001) | Review synthesis | Population note |
| Diagnostic confirmation | Diagnosis is confirmed by genetic testing for AR CAG-repeat expansion; suspicion arises from adult male with slowly progressive LMN syndrome plus bulbar/endocrine features (pqac-00000002, pqac-00000007) | Human consensus guideline; review | Repeat expansion assay |
| Electrophysiology/labs | EMG typically shows diffuse motor neuron involvement with sensory abnormalities; CK/CPK is often elevated, sometimes markedly (pqac-00000002, pqac-00000007) | Human consensus guideline; review | LOINC/EMG concept; CHEBI:17347 creatine kinase |
| Imaging/functional diagnostics | Muscle MRI/fat fraction measures, quantitative muscle testing, 2-minute and 6-minute walk tests, AMAT, SBMAFRS/m-SBMAFRS are used in studies and trials (pqac-00000000, pqac-00000011, pqac-00000012, pqac-00000015) | Human review; clinical trial records | SBMAFRS; AMAT; 6MWT |
| Biomarkers | Serum creatinine is a promising progression biomarker and may decline before weakness onset; CK and muscle/fat MRI are also used (pqac-00000000, pqac-00000001, pqac-00000009) | Human review | CHEBI:16737 creatinine |
| Differential diagnosis | ALS, SMA/non-5q SMA, myopathies, and neuropathies are key differentials (pqac-00000007) | Human clinical review | Differential diagnosis note |
| Standard management | No approved disease-modifying therapy established; care is multidisciplinary and symptomatic, emphasizing physiotherapy, speech therapy, nutritional support, aspiration/respiratory care, pain management, and endocrine/metabolic monitoring (pqac-00000002, pqac-00000010) | Human consensus guideline; review | NCIT supportive care; speech therapy; physiotherapy |
| Hormonal therapy evidence | Anti-androgen approaches have biologic rationale and some signal, but no established therapy; dutasteride trial and leuprorelin studies did not establish a standard of care (pqac-00000000, pqac-00000010, pqac-00000011) | Review; clinical trial registry | NCIT dutasteride; leuprorelin |
| Exercise/rehabilitation | Exercise is used supportively; high-intensity/functional exercise has been explored in interventional studies (pqac-00000010) | Human review | NCIT rehabilitation |
| Recent/active trial: NIDO-361 | Phase 2 PIONEER KD, randomized placebo-controlled, 54 participants, oral NIDO-361 for 12 months; endpoints include lean muscle volume, m-SBMAFRS, 2MWT/6MWT, actigraphy (pqac-00000012) | ClinicalTrials.gov record | NCT06411912 |
| Recent/active trial: AJ201 | Phase 1/2a randomized placebo-controlled study, 25 participants, oral AJ201 600 mg/day for 12 weeks; endpoints include safety and change in mutant AR protein in skeletal muscle (pqac-00000014) | ClinicalTrials.gov record | NCT05517603 |
| Recent/active trial: clenbuterol | Phase 2 placebo-controlled BetaSBMA trial, recruiting, estimated n=90, 48-week clenbuterol; primary endpoint 6MWT, with QoL and serum creatinine secondary measures (pqac-00000015) | ClinicalTrials.gov record | NCT06169046 |
| Recent/active trial: mexiletine | Phase 2/3 Med-SBMA trial, recruiting, estimated n=68; mexiletine 300 mg/day for 12 weeks, outcomes include ALSFRS-R, SBMAFRS, tongue pressure, FVC, PEF (pqac-00000013) | ClinicalTrials.gov record | NCT06862596 |
| Historical trial: dutasteride | Completed phase 2 NIH placebo-controlled trial; aimed to test 0.5 mg/day for 24 months with QMT primary outcome and QoL/functional secondary outcomes (pqac-00000011) | ClinicalTrials.gov record | NCT00303446 |
| Historical trial: BVS857 | Completed phase 2 placebo-controlled study, 37 participants; evaluated safety and thigh muscle volume by MRI (pqac-00000016) | ClinicalTrials.gov record | NCT02024932 |
| Model systems | Drosophila, transgenic/knock-in mice, and cellular systems including ASO-responsive models have been used; fly and mouse studies supported AF2 modulation, peripheral AR silencing, and Src inhibition (pqac-00000020, pqac-00000017, pqac-00000019) | Animal and in vitro primary studies | MGI mouse models; Drosophila model |
| Prevention/genetic counseling | No primary prevention for disease occurrence once expansion is inherited; useful measures are genetic counseling, cascade testing, and reproductive counseling around X-linked transmission (inferred from established genetic diagnosis and counseling relevance in reviews) (pqac-00000002, pqac-00000006) | Human consensus guideline; review | Genetic counseling; X-linked risk counseling |


*Table: This table condenses the key disease-knowledge-base fields for spinal and bulbar muscular atrophy/Kennedy disease, including identifiers, genetics, phenotypes, mechanism, epidemiology, diagnostics, management, and recent trials. It is designed for rapid curation while keeping claims conservative and tied to cited conversation evidence.*