| Category | Key items | High-value statistics/data | Key sources |
|---|---|---|---|
| Disease identifiers | Rubinstein–Taybi syndrome (RSTS/RTS); OMIM #180849 (RSTS1, CREBBP-related), OMIM #613684 (RSTS2, EP300-related); named for Rubinstein and Taybi; chromatinopathy / epigenetic disorder | >800 publications noted by 2024 consensus; incidence generally cited as ~1:100,000–1:125,000 births | (pqac-00000044, pqac-00000002) |
| Causal genes and inheritance | Autosomal dominant disorder caused mainly by heterozygous pathogenic variants in **CREBBP** and **EP300**; most cases are de novo; rare familial transmission and mosaicism reported | CREBBP explains ~55–75% of cases; EP300 ~8–11%; complete gene deletions ~2–3%; ~5–20% to ~30% remain without a molecular diagnosis depending on cohort/series; empirical recurrence risk for unaffected parents with one affected child ~0.5–1%; affected parent transmission risk 50% | (pqac-00000011, pqac-00000002, pqac-00000008, pqac-00000006) |
| Variant spectrum | Loss-of-function predominates; SNVs, indels, splice variants, CNVs, whole-gene deletions, rare mosaic variants; CREBBP missense clustering in HAT domain supports domain-critical pathogenicity | In a 395-referral cohort: 129 CREBBP P/LP and 16 EP300 P/LP variants; 145 molecular diagnoses (37%); 103/133 variants novel; 17/19 likely pathogenic CREBBP missense variants were in the HAT domain | (pqac-00000005, pqac-00000006, pqac-00000013) |
| Core phenotype: growth and craniofacial | Characteristic face, growth disturbance, developmental delay/intellectual disability, distal limb anomalies | Molecularly confirmed cohorts (CREBBP vs EP300): postnatal growth retardation 75% vs 66%; microcephaly 54% vs 87%; highly arched eyebrows 85% vs 65%; downslanted palpebral fissures 79% vs 56%; convex nasal ridge 81% vs 44%; columella below alae nasi 88% vs 92%; typical smile 94% vs 47%; highly arched palate 77% vs 67% | (pqac-00000044, pqac-00000000) |
| Core phenotype: limbs and multisystem involvement | Broad/angulated thumbs and halluces; hypertrichosis; cardiac, urinary, neurologic, GI, behavioral involvement | Broad thumbs 96% vs 69%; angulated thumbs 49% vs 2%; broad halluces 95% vs 81%; broad fingertips 87% vs 22%; hypertrichosis 76% vs 51%; cardiovascular anomalies 35% vs 26%; urinary tract anomalies 28% vs 24%; constipation 76% vs 54%; seizures 25% vs 10%; intellectual disability 99% vs 94%; autism/ASD 49% vs 25% | (pqac-00000044, pqac-00000000) |
| Immunologic phenotype | Recurrent infections, antibody defects, syndromic immunodeficiency in a substantial subset; B-cell abnormalities highlighted | In 97 patients: recurrent/severe infections 72.1%; autoimmune/autoinflammatory complications 12.3%; lymphoproliferation 8.2%; syndromic immunodeficiency 46.4%; antibody defects 11.3%; immunoglobulin replacement 16.4%; antibiotic prophylaxis 8.2%; immunosuppressive therapy 9.8% | (pqac-00000004) |
| Behavioral / neuropsychiatric features | Anxiety, OCD-like symptoms, hyperactivity/inattention, stereotypies, challenging behavior, adaptive-function impairment across lifespan; RSTS2 tends to have milder adaptive impairment but more social phobia | Caregiver study: n=71, ages 1–61; behavioral issues 88%; OCD diagnosis 21%; anxiety diagnosis 34%; 82% had mild-to-severe OCD-like symptoms; 90% of RSTS1 vs 73% of RSTS2 had elevated OCD-like symptoms; RSTS2 had higher social phobia and better adaptive scores; school-age group showed peak challenging behaviors | (pqac-00000025, pqac-00000026, pqac-00000024, pqac-00000029) |
| Clinical diagnostic criteria | 2024 international consensus uses weighted craniofacial, skeletal, growth, and development features; cardinal score requires 2 of 4 groups positive, including skeletal or craniofacial | Definitive clinical diagnosis: score ≥12 + positive cardinal score; likely: 8–11 + positive cardinal score; possible: 5–7 + negative cardinal score; both likely and possible categories warrant CREBBP/EP300 testing | (pqac-00000009, pqac-00000011, pqac-00000043) |
| Recommended molecular testing | If RSTS clinically suspected: first-line targeted CREBBP/EP300 testing by Sanger + MLPA or high-throughput methods; if not specifically suspected but ID/malformations present: aCGH/WES/WGS first-tier; RNA studies for splice uncertainty; mosaicism assessment across tissues; methylation/episignature can aid unresolved cases | Consensus specifically recommends CREBBP/EP300 molecular analysis for likely/possible clinical diagnoses; prenatal molecular testing mainly when familial variant/previously affected child is known | (pqac-00000013, pqac-00000008, pqac-00000009) |
| DNA methylation / episignature diagnostics | Genome-wide methylation signatures (EpiSign) are clinically useful adjuncts for variant interpretation and unresolved neurodevelopmental cases; CREBBP and EP300 are included among genes with established episignatures | EpiSign v3 compares against 57 DNAm profiles spanning 65 syndromes; SVM-based MVP score >0.01 triggers secondary review; study table includes CREBBP/EP300 with RSTS-related diagnostic calls | (pqac-00000038, pqac-00000039, pqac-00000013) |
| Molecular mechanism: core disease biology | CBP/CREBBP and p300/EP300 are lysine acetyltransferase (KAT/HAT) transcriptional coactivators governing histone acetylation, chromatin remodeling, and transcriptional regulation; RSTS is a chromatinopathy | Reported pathogenic variant counts in review: ~500 CREBBP and 118 EP300; HAT-domain missense enrichment is strong evidence for pathogenicity | (pqac-00000002, pqac-00000005, pqac-00000015) |
| Omics mechanism: neuronal differentiation defect | iPSC-derived neuron multi-omics identified altered histone acetylation and delayed maturation during neural progenitor → immature neuron transition | 25 altered acetylated histone residues; 2,973 DEGs overall; 2,454 DEGs at D20; ~82.5% of all DEGs concentrated at D20; ~75% of all DEGs unique to D20; residues repeatedly implicated include H2BK5, H2BK11/43/46/108, H3K18, H3K23, H3K27, H3K56, H3K79, H3K122, H2AK95, H4K77 | (pqac-00000019, pqac-00000021, pqac-00000016, pqac-00000017, pqac-00000020) |
| Mechanistic pathway: HSF2 / stress / adhesion | CBP/EP300 acetylate and stabilize **HSF2**; RSTS-associated CBP/p300 dysfunction lowers HSF2, impairing chaperone/stress responses and N-cadherin–dependent neuroepithelial integrity | Key acetylated HSF2 lysines include K128, K135, K197; reduced HSF2 lowers HSP70/HSP90/HSP110-related responses and N-cadherin; low-dose bortezomib (5–10 nM) restored HSF2 and rescued HSP110/N-cadherin expression in cell models; defects reproduced in iNPCs and cortical organoids | (pqac-00000033, pqac-00000030, pqac-00000031, pqac-00000035, pqac-00000034) |
| Natural history / demographics | Usually congenital/early-childhood onset; many cases recognized neonatally; EP300-related disease can be milder/less typical | Consensus notes 86% present within the first month of life; equal sex distribution reported in immunology cohort summary; adults survive into later life, though morbidity depends on associated anomalies | (pqac-00000008, pqac-00000004, pqac-00000003) |
| Key trial / translational study: sodium valproate | **NCT01619644 (RUBIVAL)** phase 2 randomized, double-blind trial of oral sodium valproate vs placebo in genetically confirmed RSTS | Completed; enrolled 41; ages 6–21; sodium valproate 30 mg/kg/day for 1 year; primary endpoint was ≥1-point improvement in at least one long-term memory subtest; included imaging and histone-acetylation biomarker outcomes | (pqac-00000042) |
| Key trial / translational study: acetylome biomarkers | **NCT04122742 (GENEPI)** observational Bordeaux study using patient-derived cells to define acetylation profiles as epigenetic markers for CREBBP/EP300 variant causality | Recruiting/ongoing in registry; target enrollment 154; start 2019-10-08; estimated completion Oct 2025; uses blood/skin biopsy, iPSC neuronal differentiation, LC-MS/MS acetylome profiling, ChIP-seq, RNA-seq, and CRISPR-corrected isogenic lines | (pqac-00000040, pqac-00000041) |


*Table: This table condenses the highest-yield disease, genotype, phenotype, diagnostic, mechanistic, and clinical-trial facts for Rubinstein–Taybi syndrome using only the gathered evidence. It is designed to support rapid knowledge-base curation with direct traceability to the cited context IDs.*