| Domain | Best-supported finding | Quantitative evidence | Evidence type/date |
|---|---|---|---|
| Identifiers | Nicolaides-Baraitser syndrome is a Mendelian neurodevelopmental disorder; available disease identifiers include MONDO:0011053, OMIM 601358, Orphanet 3051 | MONDO:0011053; OMIM 601358; Orphanet 3051 (pqac-00000000, pqac-00000006) | Disease-resource association/Open Targets and human clinical letter, 2016 |
| Cause / inheritance | Core cause is de novo heterozygous non-truncating SMARCA2 variation, usually in the ATPase/helicase region, consistent with autosomal-dominant sporadic disease | 61/61 analyzed cases sporadic; SMARCA2 mutations in 34/37 clinically typical patients and 2/7 less typical patients in early grouped analyses; >50% (36/61, 59%) in C-terminal helicase region (pqac-00000001, pqac-00000002, pqac-00000007) | Human cohort/review, 2014 |
| Intellectual disability | Intellectual disability is universal and often moderate-to-severe | Mild 18.0%, moderate 36.1%, severe 45.9% among 61 cases (pqac-00000016) | Molecularly confirmed 61-case cohort, 2014 |
| Seizures | Epilepsy is a major feature with usual onset in infancy/early childhood | 39/61 (63.9%); median onset 18 months, range 0–168 months; review text also notes typical onset 1–2.5 years (pqac-00000004, pqac-00000016) | Molecularly confirmed cohort/review, 2014 |
| Speech | Severe speech impairment is common, including absent speech and later decline | Absent speech 19/60 (31.7%); speech decline 9/42 (21.4%); first words median 24 months, range 10–96 months (pqac-00000016) | Molecularly confirmed 61-case cohort, 2014 |
| Growth / stature | Postnatal growth impairment is common | Short stature 30/56 (53.6%); reduced weight 24/46 (52.2%); birth weight < -2 SD in 19/57 (33.3%); birth length < -2 SD in 8/38 (21.1%) (pqac-00000001, pqac-00000003, pqac-00000016) | Molecularly confirmed cohort/review, 2014 |
| Microcephaly | Microcephaly often emerges or becomes more evident over time | 34/52 (65.4%) later in life; 7/30 (23%) at birth (pqac-00000003, pqac-00000016) | Molecularly confirmed cohort/review, 2014 |
| Hypotonia / motor delay | Hypotonia and delayed gross motor milestones are frequent | Hypotonia 19/51 (37.3%); sitting median 8 months (range 6–20); walking median 18 months (range 10–60) (pqac-00000016) | Molecularly confirmed 61-case cohort, 2014 |
| Feeding / skin / organ findings | Supportive morbidity includes feeding problems, eczema, and occasional cardiac/hearing involvement | Feeding problems 23/49 (46.9%); eczema 22/58 (37.9%); cardiac defects 6/61 (9.8%); hearing loss 4/59 (6.8%) (pqac-00000015) | Molecularly confirmed cohort table, 2014 |
| Mechanism | NCBRS is a BAFopathy caused by SMARCA2 dysfunction affecting chromatin remodeling and neural differentiation; engineered human stem-cell models support enhancer retargeting rather than simple haploinsufficiency | In engineered hESC-derived neural progenitors with SMARCA2 K755R/+ or R1159Q/+ mutations, neural differentiation was severely impaired; ~97% of upregulated genes with increased accessibility were FRA2-bound (pqac-00000010, pqac-00000011, pqac-00000012) | Experimental human hESC/NPC study, 2019 |
| Methylation diagnostics | Peripheral-blood DNA methylation episignatures can aid SMARCA2 variant interpretation | 429 differentially methylated CpGs in 8 NCBRS cases vs 23 controls; validation reported 100% sensitivity and 100% specificity with 8 cases and 96 controls; 9 SMARCA2 VUS assessed (pqac-00000009) | Epigenomic diagnostic study, 2019 |
| Recent diagnostic development | 2024 work supports episignatures as a practical adjunct for NDD/BAFopathy variant resolution but highlights interpretive limitations | Validation cohort 59 and test cohort 38 in a broader NDD study; 90% expected episignature recovery; intermediate SMARCA2 classifications reported in familial/VUS contexts (pqac-00000013, pqac-00000014) | Diagnostic/epigenomic studies and review, 2024 |
| Trials / implementation | No disease-modifying interventional trial was identified; current formal research implementation is observational registry participation | NCT01793168 is observational, recruiting, prospective, case-only, target enrollment 20,000 across rare diseases including NCBRS; no syndrome-specific therapeutic intervention reported (pqac-00000017) | ClinicalTrials.gov registry entry, 2010–current |


*Table: This table condenses the strongest available evidence for Nicolaides-Baraitser syndrome across identifiers, genetics, phenotype frequencies, mechanism, diagnostics, and trial status. It is useful as a quick-reference artifact for disease knowledge-base population with denominated cohort data and recent diagnostic advances.*