Synthetic cfDNA for Microdeletion and Microduplication Screening: 26 CNV Conditions
When NIPT expanded beyond trisomies, it entered far more challenging territory. Detecting a whole extra chromosome is one thing. Detecting a 3 megabase deletion on chromosome 22? That requires a fundamentally different level of precision - and validation materials that barely exist.
At Eabha Genomics, we generate synthetic cfDNA for 26 microdeletion and microduplication syndromes, including the conditions most commonly offered on expanded NIPT panels.
The Validation Crisis in CNV Screening
Consider DiGeorge syndrome (22q11.2 deletion) - the most common microdeletion, affecting 1 in 4,000 births. A laboratory wanting to validate detection might see a handful of positive cases per year. For rarer conditions like Miller-Dieker syndrome (1 in 100,000), a lab might never encounter a true positive.
Microdeletions We Cover
Commonly Screened (Expanded NIPT Panels)
| Condition | Region | Size | Our log2 | Prevalence |
|---|---|---|---|---|
| DiGeorge syndrome | 22q11.2 | 3.2 Mb | -0.11 | 1 in 4,000 |
| Cri du Chat | 5p | Terminal | -0.10 | 1 in 50,000 |
| Williams syndrome | 7q11.23 | 1.4 Mb | -0.07 | 1 in 10,000 |
| Prader-Willi syndrome | 15q11.2 | ~5 Mb | -0.09 | 1 in 15,000 |
| Angelman syndrome | 15q11.2 | ~5 Mb | -0.09 | 1 in 15,000 |
| 1p36 deletion | 1p36 | Variable | -0.11 | 1 in 5,000 |
Additional Clinically Relevant Deletions
| Condition | Region | Our log2 | Prevalence |
|---|---|---|---|
| Wolf-Hirschhorn | 4p16.3 | -0.14 | 1 in 50,000 |
| Smith-Magenis | 17p11.2 | -0.11 | 1 in 25,000 |
| Jacobsen syndrome | 11q24 | -0.12 | 1 in 100,000 |
| 16p11.2 deletion | 16p11.2 | -0.43 | 1 in 2,000 |
| Miller-Dieker | 17p13.3 | -0.12 | 1 in 100,000 |
| Koolen-de Vries | 17q21.31 | -0.10 | 1 in 55,000 |
Neurodevelopmental Risk CNVs
| Condition | Region | Our log2 | Association |
|---|---|---|---|
| 15q11.2 BP1-BP2 | 15q11.2 | -0.08 | Incomplete penetrance |
| 15q13.3 deletion | 15q13.3 | -0.10 | Epilepsy risk |
| 3q29 deletion | 3q29 | -0.24 | Psychiatric phenotype |
| NRXN1 deletion | 2p16.3 | -0.10 | Autism/schizophrenia risk |
Microduplications We Cover
| Condition | Region | Our log2 | Prevalence |
|---|---|---|---|
| 22q11.2 duplication | 22q11.2 | +0.10 | 1 in 700 |
| 7q11.23 duplication | 7q11.23 | +0.08 | Rare |
| Potocki-Lupski | 17p11.2 | +0.10 | 1 in 25,000 |
| 16p11.2 duplication | 16p11.2 | +0.09 | 1 in 2,000 |
The Technical Challenge
Microdeletions are harder to detect than aneuploidies because:
- Smaller signal: A 3 Mb deletion is 2% of a chromosome vs. the whole chromosome for trisomy
- Lower fetal fraction impact: The proportional change in cfDNA is much smaller
- GC bias effects: Many deletion regions have unusual GC content
Our synthetic samples are generated with these challenges in mind - reference-backed sequences with correct GC profiles, precise deletion boundaries, and configurable fetal fractions.
Why This Matters Commercially
Labs offering expanded NIPT face regulatory and clinical scrutiny:
- How did you validate 22q11.2 detection? "We used 50 synthetic positive samples covering fetal fractions from 4-20%."
- What's your PPV for Williams syndrome? Demonstrate analytical sensitivity with controlled test sets.
Get Started
Our microdeletion/microduplication panel includes 26 conditions. Contact us to discuss your CNV validation needs, or explore our full conditions database.