| Domain | Supported finding | Evidence strength/limitations | Suggested ontology terms |
|---|---|---|---|
| Genomic lesion / NAHR | Germline interstitial duplication of 10q22.3–q23.2/q23.3; recurrent approximately 7.2–7.4 Mb rearrangements can be bounded by low-copy repeats LCR3 and LCR4, consistent with non-allelic homologous recombination. Larger and unique-breakpoint duplications also occur. | Strong evidence for the structural lesion; LCR-mediated NAHR is strongly supported for recurrent events. Breakpoints vary, so each case requires genome-build-specific coordinates. (pqac-00000000, pqac-00000004, pqac-00000006) | structural chromosome anomaly; chromosomal duplication; GO:0090200 — positive regulation of release of sister chromatid cohesion; GO:0006310 — DNA recombination |
| Neurodevelopment | Developmental delay, motor delay, intellectual disability, and learning difficulties are recurrently reported. In one three-case tabulation, developmental delay occurred in all three individuals. | Moderate case-series evidence but very small, clinically ascertained samples; severity is variable and additional CNVs sometimes confound attribution. (pqac-00000000, pqac-00000001, pqac-00000008) | HP:0012758 — Neurodevelopmental delay; HP:0001263 — Global developmental delay; HP:0001249 — Intellectual disability; HP:0001270 — Motor delay |
| Speech and language | Delayed speech and language development is a prominent manifestation; two of three tabulated duplication cases had speech delay. | Moderate evidence from a small cohort; no population-based frequency or standardized language testing is available. (pqac-00000000, pqac-00000002) | HP:0000750 — Delayed speech and language development |
| Behavior / social interaction | Impaired social interaction and behavioral abnormalities have been described; autism, hyperactivity, and aggression occur in the broader 10q22q23 cohort but cannot all be assigned specifically to duplication carriers. | Limited duplication-specific evidence; impaired social interaction occurred in two of three tabulated cases, while broader behavioral counts mix deletion and duplication cases. (pqac-00000000, pqac-00000003, pqac-00000009) | HP:0000729 — Autistic behavior; HP:0000752 — Hyperactivity; HP:0000718 — Aggressive behavior; impaired social interaction |
| Craniofacial morphology | Reported features include broad forehead, deep-set eyes, upslanting palpebral fissures, smooth philtrum, thin upper lip, full cheeks, micrognathia, anteverted nares, and large widely spaced teeth. | Moderate descriptive evidence for a recognizable but variable pattern; none is obligatory or independently diagnostic. (pqac-00000000, pqac-00000002, pqac-00000003) | HP:0000337 — Broad forehead; HP:0000490 — Deeply set eye; HP:0000582 — Upslanted palpebral fissure; HP:0000319 — Smooth philtrum; HP:0000219 — Thin upper lip vermilion; HP:0000347 — Micrognathia; HP:0000463 — Anteverted nares |
| Eyes and ears | Strabismus, hypotelorism, low-set or prominent ears, and recurrent infant ear infections have been reported. | Limited case-series evidence; visual problems in one NRG3-duplication case were considered more likely related to prematurity. (pqac-00000000, pqac-00000003, pqac-00000010) | HP:0000486 — Strabismus; HP:0000601 — Hypotelorism; HP:0000369 — Low-set ears; HP:0000413 — Atresia of the external auditory canal not supported and should not be assigned; recurrent otitis media |
| Congenital heart disease / microcephaly | Congenital heart disease and microcephaly were associated with an 18.6 Mb de novo duplication; tetralogy of Fallot was reported with an intragenic NRG3 duplication. | Rare single-case associations only; no causal gene, penetrance estimate, or reliable frequency has been established. Growth and head circumference are otherwise variable. (pqac-00000001, pqac-00000010, pqac-00000011) | HP:0001627 — Abnormal heart morphology; HP:0001636 — Tetralogy of Fallot; HP:0000252 — Microcephaly |
| Penetrance / inheritance | Both de novo and inherited duplications occur, including maternal and paternal transmission; apparently healthy relatives can carry overlapping duplications. | Strong evidence for variable expressivity and probable incomplete penetrance, but penetrance cannot be quantified. Some inherited small duplications were judged likely non-pathogenic. (pqac-00000000, pqac-00000002, pqac-00000009, pqac-00000011) | HP:0003829 — Incomplete penetrance; variable expressivity; autosomal inheritance |
| Candidate dosage mechanisms | Increased dosage across a multigene interval is the leading hypothesis. BMPR1A, NRG3, GRID1, PTEN, and WAPL are biologically plausible candidates, but no individual gene has been proven to drive the duplication phenotype. | Hypothesis-level evidence only. Findings from 10q22q23 deletions, especially PTEN/BMPR1A loss phenotypes, must not be extrapolated to duplications. (pqac-00000008, pqac-00000010, pqac-00000011) | gene dosage; GO:0006355 — regulation of DNA-templated transcription; GO:0007399 — nervous system development; GO:0007507 — heart development |
| Diagnostics | Chromosomal microarray—array CGH or SNP array—is the primary detection method. Parental testing clarifies inheritance; FISH or MLPA may confirm selected findings, while sequencing-based CNV analysis or genome sequencing may refine breakpoints and detect additional variants. | Strong clinical-laboratory evidence for CMA detection. Conventional karyotyping can miss microduplications; exact interpretation requires coordinates, genome build, gene content, inheritance, phenotype, and comparison with curated CNV databases. (pqac-00000004, pqac-00000005, pqac-00000007) | chromosomal microarray analysis; array comparative genomic hybridization; fluorescence in situ hybridization; multiplex ligation-dependent probe amplification; genome sequencing |
| Management | Care is supportive and phenotype-directed: developmental assessment, early speech/language therapy, physical and occupational therapy, behavioral assessment, audiology and ophthalmology evaluation, and cardiac evaluation when clinically indicated. | Expert-practice inference from manifestations; no syndrome-specific guideline, controlled treatment study, or response-rate evidence was identified. (pqac-00000008, pqac-00000009) | NCIT: C61560 — Supportive Care; NCIT: C15329 — Speech Therapy; NCIT: C15330 — Physical Therapy; occupational therapy; early intervention |
| Unsupported or unavailable domains | No established environmental, infectious, lifestyle, metabolic, immune, or protective factors; no validated biochemical biomarker, syndrome-specific drug, pharmacogenomic rule, gene/RNA/cell therapy, clinical trial, natural animal disease, whole-duplication model, single-cell study, spatial transcriptomic study, or diagnostic multi-omics signature was identified. | Absence of published evidence is not proof of biological absence; the literature consists mainly of old, small human case series, with no syndrome-specific 2023–2024 primary research retrieved. (pqac-00000008, pqac-00000009, pqac-00000010, pqac-00000011) | Not applicable / no supported ontology annotation beyond chromosomal duplication and phenotype-directed care |


*Table: Compact evidence map for 10q22.3q23.3 microduplication syndrome, separating supported duplication findings from rare associations and unsupported domains. Ontology identifiers are included only where sufficiently established.*