For any parent, learning after delivery that their baby may have a serious chromosomal condition can be heartbreaking and scary. Unfortunately, some conditions are very difficult to detect during pregnancy without invasive diagnostic testing, which may not be indicated for a young, healthy pregnant person with a typically progressing pregnancy.   

Such is the case with the 22q11.2 microdeletion syndrome, a relatively common and potentially serious chromosomal abnormality. 22q, as it is colloquially called, may occur as frequently as 1 in 4000 live births and is caused by a small missing piece of chromosome 22.¹ It can result in a wide range of health problems, such as congenital heart defects, immune system disorders, facial differences, learning difficulties, and behavioral and emotional issues.²  Maternal age does not affect the likelihood of the 22q microdeletion. 

Typically, the way to diagnose 22q prenatally is through chorionic villus sampling or an amniocentesis. Less invasive options like prenatal cell-free DNA (cfDNA) screens can also be used to help identify the microdeletion. According to a study in Genes (Basel), cfDNA screens have “a 70–83% detection rate and a 40–50% positive predictive value (PPV) for most associated 22q microdeletions.”³  The small size of the 22q microdeletion makes it technically challenging to detect using prenatal cell-free DNA. Thus, the value of using cfDNA screens for 22q has been marginal. 

Until now.  

More Reliable Results 

A study by Myriad Genetics, published in April, found that Prequel^® Prenatal Screen with AMPLIFY^TM technology “yields a PPV for the 22q microdeletion higher than any previous studies have reported, and comparable to that for common autosomal trisomies.”⁴ 

In a recent presentation, Dale Muzzey, PhD, Chief Scientific Officer at Myriad, summarized the findings this way: “We followed up with providers regarding their patients who screened positive for 22q. Among the 76 patients who screened positive for the 22q microdeletion, we were able to obtain diagnostic testing results for 22, all of which were confirmed positive.  We observed 100% PPV. There’s a confidence interval on that of 84.6% – 100%.” Previous data using other laboratory methods have yielded a PPV of approximately half that, around 53%.⁵ 

Clear Benefits for Healthcare Providers and Patients 

The benefits to a high PPV are, well, myriad. For example, Driscoll (2001) wrote on the benefits of early 22q detection:  

• Couples can opt to pursue diagnostic testing. 
• Couples and their physicians can prepare for the delivery of a child with the deletion and anticipate associated problems such as hypocalcemia, immune deficiencies, and feeding difficulties in the newborn period.  
• Delivery at a tertiary care center should also be considered, especially when a complex cardiac lesion is detected antenatally.  
• Infants and children with 22q deletions may benefit from early intervention based on the evaluation and long-term care by a multidisciplinary team of pediatric specialists aware of the wide spectrum of medical, neuropsychologic, and cognitive problems these children can encounter.  
• Parent support groups are available in the United States, Canada, Europe, and Australia, as well as online, and can provide families with additional information and support.”⁶  

Prequel Prenatal Screen with AMPLIFY technology offers healthcare providers and patients a more accurate and reliable prenatal screening for 22q and other chromosomal abnormalities. This can help reduce anxiety, increase confidence, and give families time to plan and prepare. 

If you want to learn more about Prequel Prenatal Screen with AMPLIFY technology, please visit myriad.com/prequel. 

REFERENCES 

1. Devriendt K, Fryns J-P, Mortier G, Van Thienen M-N, Keymolen K . The annual incidence of DiGeorge/velocardiofacial syndrome. J Med Genet 1998; 35: 789–790. 
2. DiGeorge syndrome (22q11.2 deletion syndrome) – Symptoms and causes. Mayo Clinic. Accessed February 22, 2024. https://www.mayoclinic.org/diseases-conditions/digeorge-syndrome/symptoms-causes/syc-20353543#:~:text=Medical%20problems%20commonly%20related%20to 
3. Blagowidow N, Nowakowska B, Schindewolf E, et al. Prenatal Screening and Diagnostic Considerations for 22q11.2 Microdeletions. Genes (Basel). 2023;14(1):160. Published 2023 Jan 6. doi:10.3390/genes14010160 
4. Johansen Taber K, Hammer C, Pierson S, et al. High positive predictive value 22q11.2 microdeletion screening by prenatal cell-free DNA testing that incorporates fetal fraction amplification. Prenatal Diagnosis. Published April 16, 2024. https://doi.org/10.1002/pd.6562 
5. Dar P, Norton ME. Performance of noninvasive prenatal screening for 22q11.2 deletion syndrome in the SMART study. American Journal of Obstetrics and Gynecology. 2022;227(1):124-125. doi: https://doi.org/10.1016/j.ajog.2022.01.036 
6. Driscoll, D. Prenatal diagnosis of the 22q11.2 deletion syndrome. Genet Med 3, 14–18 (2001). https://doi.org/10.1097/00125817-200101000-00004