| Category | Specific item | Value/statement | Source (author year) | URL | Evidence citation id (pqac-...) |
|---|---|---|---|---|---|
| Identifier | Disease names / synonyms | 22q11.2 deletion syndrome; DiGeorge syndrome; velocardiofacial syndrome (VCFS) | Soster 2023 | https://doi.org/10.3389/fgene.2023.1146669 | (pqac-00000019) |
| Identifier | OMIM identifiers mentioned | DiGeorge syndrome OMIM #188400; VCFS OMIM #192430 | Soster 2023 | https://doi.org/10.3389/fgene.2023.1146669 | (pqac-00000019) |
| Identifier | Alternate OMIM usage in review literature | 22q11DS listed as OMIM #192430/#188400 | Snihirova 2022 | https://doi.org/10.3390/genes13112003 | (pqac-00000021) |
| Prevalence | Live-birth prevalence range | Approximately 1 in 3,000 to 1 in 6,000 live births; often summarized around 1 in 4,000 | Mustillo 2023; Biggs 2023 | https://doi.org/10.1007/s10875-022-01418-y; https://doi.org/10.1007/s11882-023-01071-4 | (pqac-00000000, pqac-00000002) |
| Prevalence | Review estimate including fetal prevalence | 1:2,000 to 1:6,000 live births; ~1:1,000 in unselected fetuses; up to ~1:100 in fetuses with major structural defects | Szczawińska-Popłonyk 2023 | https://doi.org/10.3390/ijms24098317 | (pqac-00000005, pqac-00000008) |
| Prevalence | Population-based prevalence | 1 in 3,672 for 22q11.2 deletions in Danish population study | Olsen 2018 | https://doi.org/10.1016/S2215-0366(18)30168-8 | (pqac-00000013) |
| Prevalence | Combined prenatal/postnatal minimum estimate | Estimated prevalence 1 in 4,558 births in Victoria cohort | Hui 2020 | https://doi.org/10.1093/humrep/dez286 | (pqac-00000013) |
| Genetics | Typical deletion proportion | ~85% carry the typical ~3 Mb deletion | Cillo 2024 | https://doi.org/10.3390/genes15030321 | (pqac-00000011) |
| Genetics | Typical proximal deletion classes | ~90% have 2.54 Mb A-D deletion; ~5% A-B; ~2% A-C; ~5% smaller nested B-D or C-D deletions | Szczawińska-Popłonyk 2023 | https://doi.org/10.3390/ijms24098317 | (pqac-00000008) |
| Genetics | Mechanism | Recurrent deletion mediated by non-allelic homologous recombination between low-copy repeats (LCR22s) | Szczawińska-Popłonyk 2023; Cillo 2024 | https://doi.org/10.3390/ijms24098317; https://doi.org/10.3390/genes15030321 | (pqac-00000008, pqac-00000060) |
| Genetics | De novo vs inherited | ~90–95% de novo; ~10% inherited/autosomal dominant familial cases | Mustillo 2023; Szczawińska-Popłonyk 2023; Cillo 2024 | https://doi.org/10.1007/s10875-022-01418-y; https://doi.org/10.3390/ijms24098317; https://doi.org/10.3390/genes15030321 | (pqac-00000000, pqac-00000008, pqac-00000011) |
| Genetics | Important genes highlighted | TBX1 and DGCR8 are repeatedly highlighted as key dosage-sensitive genes; CRKL also implicated for renal/cardiac phenotypes | Du 2020; Cillo 2024 | https://doi.org/10.3389/fgene.2019.01365; https://doi.org/10.3390/genes15030321 | (pqac-00000054, pqac-00000056, pqac-00000061) |
| Key phenotype frequencies | Congenital heart disease (CHD) | ~75% overall in 2024 review; other reviews cite ~60–80% in children | Cillo 2024; Szczawińska-Popłonyk 2023 | https://doi.org/10.3390/genes15030321; https://doi.org/10.3390/ijms24098317 | (pqac-00000031, pqac-00000032) |
| Key phenotype frequencies | Specific CHD lesions | Tetralogy of Fallot 20%; VSD 14%; interrupted aortic arch 10%; pulmonary atresia with VSD 9%; truncus arteriosus 9%; ASD 3% | Sauter 2025 | https://doi.org/10.1136/jmg-2025-110624 | (pqac-00000000) |
| Key phenotype frequencies | Immune deficiency / thymic abnormality | 50–70% with thymic hypoplasia/ectopy/immune deficiency; guideline states 67–80% have some T-cell lymphopenia | Cillo 2024; Mustillo 2023 | https://doi.org/10.3390/genes15030321; https://doi.org/10.1007/s10875-022-01418-y | (pqac-00000010, pqac-00000000) |
| Key phenotype frequencies | Complete DiGeorge / congenital athymia | <0.5% to 1.5% of cases | Biggs 2023; Cillo 2024 | https://doi.org/10.1007/s11882-023-01071-4; https://doi.org/10.3390/genes15030321 | (pqac-00000002, pqac-00000033) |
| Key phenotype frequencies | Hypocalcemia / hypoparathyroidism | ~35% in one 2024 review; 50–65% in another review; 50% in 2024 overview of classic triad manifestations | Cillo 2024 | https://doi.org/10.3390/genes15030321 | (pqac-00000010, pqac-00000011, pqac-00000033) |
| Key phenotype frequencies | Palatal anomalies | 69–100% in 2024 review; ~30–80% in 2023 review; overt cleft palate ~11% and milder palatal defects ~65% | Cillo 2024; Szczawińska-Popłonyk 2023 | https://doi.org/10.3390/genes15030321; https://doi.org/10.3390/ijms24098317 | (pqac-00000031, pqac-00000032, pqac-00000033) |
| Key phenotype frequencies | Developmental delay / learning problems | Approximately 70% | Cillo 2024 | https://doi.org/10.3390/genes15030321 | (pqac-00000031) |
| Key phenotype frequencies | Intellectual disability | Mild–moderate intellectual disability in about one-third of pediatric patients | Szczawińska-Popłonyk 2023 | https://doi.org/10.3390/ijms24098317 | (pqac-00000030, pqac-00000032) |
| Key phenotype frequencies | Schizophrenia / psychosis risk | Schizophrenia ~25–30% in review literature; pooled prevalence of any psychotic disorder 11.5% and schizophrenia 9.7% in meta-analysis | Cillo 2024; Provenzani 2022 | https://doi.org/10.3390/genes15030321; https://doi.org/10.1080/09540261.2022.2123273 | (pqac-00000031, pqac-00000033, pqac-00000012) |
| Prognosis | All-cause mortality risk vs unaffected siblings | Hazard ratio 8.86 (95% CI 2.87–27.37) | Van et al. 2019 | https://doi.org/10.1038/s41436-019-0509-y | (pqac-00000025, pqac-00000028) |
| Prognosis | Median age at death | 46.4 years; all observed deaths before age 70 | Van et al. 2019 | https://doi.org/10.1038/s41436-019-0509-y | (pqac-00000022, pqac-00000027) |
| Prognosis | Major cause of death | Cardiovascular causes accounted for 71% of deaths; sudden cardiac death n=12, heart failure n=7, arrhythmia n=3 | Van et al. 2019 | https://doi.org/10.1038/s41436-019-0509-y | (pqac-00000022, pqac-00000025) |
| Prognosis | CHD effect on survival | Major CHD independently increased mortality (HR 4.77 within 22q11.2DS cohort); survival to age 45 ~72% with major CHD vs ~95% without | Van et al. 2019 | https://doi.org/10.1038/s41436-019-0509-y | (pqac-00000025, pqac-00000028) |
| Prognosis | Adult chronic disease accrual | Cardiovascular disease accrual RR 3.8 vs comparators; hypertension IRR 2.98 and diabetes IRR 3.21 by age 18–24 | Malecki 2026 | https://doi.org/10.3389/fgene.2026.1737027 | (pqac-00000023) |
| Prognosis | Type 2 diabetes risk | 22q11.2 microdeletion independently associated with T2D, OR 2.44; median age at onset 32 vs 50 years in comparison group | Van et al. 2020 | https://doi.org/10.1016/j.eclinm.2020.100528 | (pqac-00000024) |
| Prognosis | Obesity / metabolic syndrome in adults | Generalized obesity 32.0%; abdominal obesity 51.5%; metabolic syndrome 33.0% | Faijer-Westerink 2025 | https://doi.org/10.1038/s41366-024-01685-2 | (pqac-00000023) |
| Diagnostics | Preferred diagnostic confirmation | Chromosomal microarray (CMA) and/or FISH are standard confirmatory tests; FISH may miss atypical nested/distal deletions | Mustillo 2023; Soster 2023 | https://doi.org/10.1007/s10875-022-01418-y; https://doi.org/10.3389/fgene.2023.1146669 | (pqac-00000045, pqac-00000040) |
| Diagnostics | FISH probes mentioned | Common probes: N25, TUPLE1/HIRA, TBX1 | Soster 2023 | https://doi.org/10.3389/fgene.2023.1146669 | (pqac-00000019, pqac-00000040) |
| Diagnostics | MLPA utility | MLPA used to validate deletion/duplication origin and identify maternal CNVs in prenatal follow-up | Cong 2025 | https://doi.org/10.1038/s41598-025-33979-4 | (pqac-00000038, pqac-00000039) |
| Diagnostics | Newborn immune screening | TREC-based newborn screening increases early detection; only ~3–15% abnormal on current cutoffs in one review | Biggs 2023 | https://doi.org/10.1007/s11882-023-01071-4 | (pqac-00000049) |
| Screening | cfDNA/NIPS PPV range in literature | Reported PPV range from 18% to >97% across studies | Soster 2023 | https://doi.org/10.3389/fgene.2023.1146669 | (pqac-00000020, pqac-00000043) |
| Screening | cfDNA/NIPS cohort performance | In 307 screen-positive samples with diagnostic testing, observed PPVs were 90.7%–99.4% | Soster 2023 | https://doi.org/10.3389/fgene.2023.1146669 | (pqac-00000019, pqac-00000040) |
| Screening | Routine NIPS performance in unselected pregnancy cohort | 22 high-risk deletion calls among 38,495 pregnancies; 17 underwent amniocentesis/CMA; PPV 47.06% (8/17); sensitivity 83.33% reported | Cong 2025 | https://doi.org/10.1038/s41598-025-33979-4 | (pqac-00000016, pqac-00000017, pqac-00000018, pqac-00000039, pqac-00000041) |
| Screening | Maternal CNV confounding | Some NIPS-positive/fetal-CMA-negative cases were explained by maternal 22q11.2 deletions | Cong 2025; Soster 2023 | https://doi.org/10.1038/s41598-025-33979-4; https://doi.org/10.3389/fgene.2023.1146669 | (pqac-00000017, pqac-00000018, pqac-00000043) |
| Screening | ACMG recommendation noted | ACMG conditionally recommends offering screening for 22q11.2 deletion syndrome to all patients | Soster 2023 | https://doi.org/10.3389/fgene.2023.1146669 | (pqac-00000020, pqac-00000041) |
| Prognosis/Treatment | Thymus implant survival | Reported survival after thymic implant 72% (76/105) in congenital athymia; functional naive T cells appear by 3–4 months, with broader reconstitution by 6–12 months | Mustillo 2023 | https://doi.org/10.1007/s10875-022-01418-y | (pqac-00000048) |
| Prognosis/Treatment | Alternative estimate for cultured thymus transplantation | 77% 1-year survival with T-cell recovery at 6–12 months reported in review summary | Cillo 2024 | https://doi.org/10.3390/genes15030321 | (pqac-00000033) |


*Table: This table compiles high-value identifiers, epidemiology, genotype architecture, phenotype frequencies, prognosis metrics, and diagnostic/screening performance for 22q11.2 deletion syndrome. It is designed as a quick-reference evidence grid for knowledge-base curation and report drafting.*