Increased nuchal translucency: results from microarray and RASopathy disorders testing.

OBJECTIVE: To determine the incidence of chromosome abnormalities, submicroscopic chromosomal microarray (CMA) abnormalities and RASopathy Disorders (RD) pathogenic variants in a cohort of pregnant patients with a nuchal translucency (NT) ≥3.5mm. We propose a clinical protocol for surveillance of this group of patients.

METHODS: A retrospective chart review was performed on patients seen at The Prenatal Diagnosis and Medical Genetics Program between January 2013 - December 2015 for NT ≥3.5mm that had chorionic villus sampling or amniocentesis. Patients underwent extensive genetic counselling prior to invasive procedures and testing. Initial genetic testing included qualitative fluorescence polymerase chain reaction (QF-PCR) for aneuploidies. If negative, patients underwent karyotype testing, CMA and DNA analysis for RD pathogenic variants which included 9 known genes. Patients also underwent detailed fetal ultrasounds and echocardiograms completed by experts in the fields.

RESULTS: A total of 226 eligible patients were identified. In 116/226 (51.3%) patients, QF-PCR identified a chromosomal aneuploidy. The remaining 110/226 (48.7%) patients had further genetic testing. Abnormal/pathogenic cytogenetic results (karyotyping and CMA) were detected in 9/110 (8.2%) of the patients along with 5 variants of unknown significance (VUS). RD testing yielded 3 pathogenic variants (3/110) for a detection rate of 2.7 % and 1 VUS. The optimal NT cut off for RD screening was 7.9 mm in this population. This article is protected by copyright. All rights reserved.