Russ Jelsema, MD, Senior Medical Director at Natera, discusses the results of the SMART study, which evaluated the performance of Single Nucleotide Polymorphism (SNP)-based Non Invasive Prenatal Testing (NIPT) for 22q11.2 deletion syndrome (22q) in a cohort of pregnant women.
22q, also known as DiGeorge or velocardiofacial syndrome, is a rare neurological disorder caused by the deletion of a portion near the middle of chromosome 22 known as q11.2. The disease is characterized by a variable clinical profile including congenital heart defects and developmental delay in most patients, a cleft palate or velopharyngeal insufficiency, hypocalcemia, immunodeficiency, autism, and psychiatric disorders.
As Dr. Jelsema explains, results from the SMART study were recently published in the American Journal of Obstetrics and Gynecology. The primary outcomes were sensitivity, specificity, positive predictive value (PPV), and negative predictive value of cell-free DNA screening for the detection of all deletions, including the classical deletion and nested deletions that are greater than 500 kb, in the 22q11.2 low-copy repeat A-D region. Secondary outcomes included the prevalence of 22q and performance of an updated cell-free DNA algorithm that was evaluated with blinding to the pregnancy outcome.
Of the 20,887 women enrolled, a genetic outcome was available for 18,289 (87.6%). Among those women, 12 cases of 22q were confirmed in the cohort, including 5 with nested deletions, yielding a prevalence of 1 in 1524. In those with an available genetic outcome, cell-free DNA screening identified 17,976 (98.3%) cases as low risk for 22q and 38 (0.2%) cases as high risk, while 275 (1.5%) cases were non-reportable. Overall, 9 of 12 cases of 22q were detected, yielding a sensitivity of 75.0%; specificity of 99.84%; positive predictive value of 23.7% ; and negative predictive value of 99.98%. None of the cases with a nonreportable result was diagnosed with 22q.
These findings suggest that 22q is much more common than previously thought; with an incidence of 1/1524 pregnancies, 22q is more prevalent than routinely screened conditions such as trisomy 13, trisomy 18, cystic fibrosis, and spinal muscular atrophy.
To learn more about 22q and other rare neurological diseases, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/