Significance of chromosome 22q11 analysis after detection of an increased first-trimester nuchal translucency

Abstract

Objective: To determine the value of performing routine fluorescent in situ hybridization (FISH) for microdeletions of chromosome 22q11 when karyotyping fetuses with increased nuchal translucency.

Design: This was a prospective observational study carried out over an 18-month period. Fetal karyotyping by chorionic villus sampling was offered to 5429 women attending for a routine booking scan in the first trimester when their nuchal translucency adjusted risk for Down syndrome was > or = 1 in 300. Cytogenetic samples were routinely tested for the 22q11 microdeletion when the nuchal translucency was > or = 3 mm.

Results: The prevalence of increased nuchal translucency > or = 2.5 mm was 180 (3.3%) and > or = 3.5 mm was 42 (0.8%). None of 75 fetuses with an increased nuchal translucency and normal karyotype demonstrated a 22q11 microdeletion on FISH analysis. In the same cohort, 3 of 20 (15%) cases of major congenital heart defects in which nuchal translucency was measured, had a nuchal translucency measurement > or = 2.5 mm.

Conclusions: Routine FISH analysis for chromosome 22q11 microdeletions at the time of chorionic villus sampling for increased first-trimester nuchal translucency is of limited value. As a significant proportion of fetuses with increased nuchal translucency will be found to have congenital heart defects later in the pregnancy, FISH analysis for chromosome 22q11 microdeletions can be targeted to fetuses with specific congenital heart defects. Tissue from the chorionic villus sampling should therefore be stored for subsequent analysis, until after detailed echocardiography is performed.