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Higher Prevalence Than Previously Estimated

Grati et al. 2015. Prenatal diagnosis (2015), 35: 801-809

A new study by Grati and colleagues indicated that 22q11.2 microdeletions are likely to be more prevalent than previously estimated.

The authors examined the prevalence of genetic deletions and duplications in 9648 chorionic villous and amniotic fluid samples that were received in a 3 year period. The authors categorized the samples to high and low risk for genetic anomalies groups. The high risk group included samples where there was i) a parent carrier of a chromosome abnormality; ii) miscarriage/intrauterine fetal death and iii) high-risk ultra-sound related indications. The low risk group included samples where i) the mother had an advanced maternal age; ii) samples were at increased risk for Down syndrome as per maternal serum screening; iii) maternal anxiety; iv) previous fetus/child with aneuploidy; v) ultrasound low-risk and vi) other low risk indications. They then performed karyotyping and measured the relative dosage of chromosomes (21, 18, 13, X and Y) and 9 genomic critical regions (including the 22q11.2 critical region).

25% of the total sample was in the high risk group while 64% of the total sample was in the low risk group. Genetic deletions and duplications accounted for 0.7% of the overall sample. About 70% of the deletions and duplications found were located in 22q11.2. The deletion was present in 1/992 of the low-risk pregnancies and the duplication was similarly present in 1/850 of the low-risk pregnancies. Moreover, maternal age was not associated with presence of deletions/duplications.

The prevalence of the 22q11.2 deletions in this study was much higher than in previous reports (~1:4000 to 1:6000). This is likely attributed to the fact that this study examined the presence of the deletions/duplications in a less-restrictive way (i.e., without taking into account the post-natal clinical presentation of the individuals). The similar prevalence between 22q11.2 deletions and duplications was as expected based on predictions from previous molecular studies.

The findings of this study have important clinical implications. Given the variable clinical expressivity of 22q11.2DS, many individuals are likely to remain undiagnosed and therefore not receive appropriate treatment. Thus, taking into account the therapeutic benefits of early detection of 22q11.2DS, prenatal diagnosis might be beneficial for this group of individuals.