Chromosomal microarray should be performed for cases of fetal short long
bones detected prenatally
Abstract
Objectives: To investigate the prevalence of pathogenic and
likely-pathogenic variants detected by chromosomal microarray analysis
(CMA), among pregnancies with fetal short long bones diagnosed by
ultrasound. Design: A retrospective study. Setting: The study was based
on national records from the Israeli Ministry of Health. Sample:
Chromosomal microarray analyses performed nationwide, during January
2016 to March 2018, for the indication of prenatal diagnosis of short
long bones (n=66). Methods: Clinical data was retrieved from genetic
counselling summary letters and from patients’ medical records. The CMA
yield was compared to two cohorts that reported the background risk.
Main outcome measure: Pathogenic/likely pathogenic CMA. Results: There
were 4 cases with a pathogenic/likely pathogenic result (6%). The rate
of chromosomal abnormalities was significantly higher compared to the
background risk for copy number variations (CNVs)
[P<0.001], [odds ratio (OR) 4.5, 95% CI 1.6-12.7],
[OR 5.8, 95% CI 2-16.2], for both isolated [OR 6.1, 95% CI
1.4-26], [OR 7.8, 95% CI 1.8-33.5], and non-isolated cases[OR
10, 95% CI 2.2-44], [OR 12.8, 95% CI 2.9-57], , and for cases in
which the lowest estimated bone length percentile was above the 3rd
percentile (below 5th percentile) [OR 23, 95% CI 6.2-87], [OR
29.9, 95% CI 8-111], . Conclusion: The yield of CMA in cases with
short long bones (both isolated and non-isolated) is significantly
higher than the background risk for chromosomal anomalies in pregnancies
with no sonographic anomalies. This suggests that CMA should be offered
in pregnancies with a diagnosis of fetal short long bones.