INVESTIGATING THE INCIDENCE OF THE 22q11.2 DELETION SYNDROME IN MISCARRIAGE

Define the incidence of segmental abnormalities associated with the 22q11.2 deletion syndrome (DS) in pregnancy loss. Fresh product of conception (POC) singleton cases over an 11-year period were reviewed. DNA extracted from POC and maternal blood samples were analyzed at a single reference laboratory by chromosomal microarray analysis (SNP-CMA) using Illumina CytoSNP-12b with bioinformatics to detect aneuploidy, full and mosaic copy number changes, deletions and duplications, uniparental isodisomy and heterodisomy, and regions of homozygosity, while evaluating for maternal cell contamination and parental origin of abnormalities. Clinical information was collected on the test requisition form. (E&I #19040-03) Of the 84,509 fresh cases with fetal results, 82 had a deletion of the 22q11.2 region: 60 had an isolated deletion; 22 had additional findings. Parental origin of the deletion was 45 maternal, 33 paternal and 4 unknown. Average gestational age: 82.9 days (range 37-241 days): 51 first trimester losses, 11 second trimester losses, and 3 third trimester losses (17 unknown). Average maternal age: 32.6 years (range 19.0-47.0 years). Deletion size range: 0.7-4.8 Mb. Cases are broken down by low-copy repeat (LCR) breakpoints A-D. (Table 1)Tabled 1Table 1. Distribution of 22q11.2 deletion cases by LCR breakpointsDeletion LCR BreakpointCases with 22q11.2 Deletion OnlyCases with Additional FindingsAverage Size, Mb (range)LCR22A to LCR22D2963.2 (2.7-4.8)*LCR22A to LCR22C2242.5 (1.9-3.2)*LCR22A to LCR22B1052.8 (1.2-3.8)*LCR22B to LCR22D111.6 (1.5-1.6)LCR22B to LCR22C310.8 (0.7-1.2)LCR22C to LCR22D00na*10 cases had an initial breakpoint including some or all of the p-arm of chromosome 22. Open table in a new tab *10 cases had an initial breakpoint including some or all of the p-arm of chromosome 22. SNP-CMA testing of POC samples provides greater resolution than karyotype allowing for detection, sizing, and parental origin of segmental abnormalities associated with the 22q11.2 DS. The 22q11.2 DS is not associated with advanced maternal age and was identified throughout all trimesters of pregnancy. In this cohort, the incidence of the 22q11.2 DS was 1/1150, higher than the published pediatric incidence (1/2000-1/4000), but similar to the published prenatal incidence (1/1000). Comparatively, the 22q11.2 DS is more common than trisomy 13 and trisomy 18 in women <39 years and <35 years respectively. Offering genetic testing that can detect the 22q11.2 DS in miscarriages allows healthcare providers to counsel patients about recurrence risk, possible cause of the loss, and parental medical management.