RT Journal Article
SR Electronic
T1 Prenatal ultrasound findings of rasopathies in a cohort of 424 fetuses: update on genetic testing in the NGS era
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 654
OP 661
DO 10.1136/jmedgenet-2018-105746
VO 56
IS 10
A1 Kyra E Stuurman
A1 Marieke Joosten
A1 Ineke van der Burgt
A1 Mariet Elting
A1 Helger G Yntema
A1 Hanne Meijers-Heijboer
A1 Tuula Rinne
YR 2019
UL http://jmg.bmj.com/content/56/10/654.abstract
AB Background This study evaluates 6 years of prenatal rasopathy testing in the Netherlands, updates on previous data and gives recommendations for prenatal rasopathy testing.Methods 424 fetal samples, sent in for prenatal rasopathy testing in 2011–2016, were collected. Cohort 1 included 231 samples that were sequenced for 1–5 rasopathy genes. Cohort 2 included 193 samples that were analysed with a 14-gene next generation sequencing (NGS) panel. For all mutation-positive samples in both cohorts, the referring physician provided detailed ultrasound findings and postnatal follow-up. For 168 mutation-negative samples in cohort 2, solely clinical information on the requisition form was collected.Results In total, 40 (likely) pathogenic variants were detected (9.4%). All fetuses showed a variable degree of involvement of prenatal findings: increased nuchal translucency (NT)/cystic hygroma, distended jugular lymph sacs (JLS), hydrops fetalis, polyhydramnios, pleural effusion, ascites, cardiac defects and renal anomalies. An increased NT was the most common finding. Eight fetuses showed solely an increased NT/cystic hygroma, which were all larger than 5.5 mm. Ascites and renal anomalies appeared to be poor predictors of pathogenic outcome.Conclusion Fetuses with a rasopathy show in general multiple ultrasound findings. The larger the NT and the longer it persists, the more likely it is to find a pathogenic variant. Rasopathy testing is recommended when the fetus shows an isolated increased NT ≥5.0 mm or when NT of ≥3.5 mm and at least one of the following ultrasound anomalies is present: distended JLS, hydrops fetalis, polyhydramnios, pleural effusion, ascites, cardiac defects and renal anomalies.