EP11.15: Prenatal diagnosis of IDH1 de novo loss: a rare disorder with growth restriction, skeletal, cerebral and heart anomalies

Isocitrate dehydrogenase (IDH) 1 loss may lead to a rare neurodevelopmental disorder called metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria, including severe skeletal and cerebral anomalies. So far, no prenatal case of IDH1 loss has been reported in literature. Point mutations in IDH1/2 genes are described in distinct cancers, premalignant diseases and rare inherited metabolic disorders. A 27-year-old Gravida I Para 0 presented at 21+1 gestational weeks for a second trimester anomaly screening. The fetal phenotype included growth restriction, cerebral abnormalities (brachycephaly with hydrocephalus internus, cerebellar and vermian hypoplasia, corpus callosum dysgenesis), thorax and pulmonary hypoplasia, heart anomalies, hypoechogenic liver and intestine, as well as shortening of the tubular bones and arthrogryposis (radial deviation of the hands, clinodactyly) (figure 1). Exome sequencing detected a de novo heterozygous loss of the IDH1 gene, encoding for the enzyme isocitrate dehydrogenase. Neither parent was a carrier of the loss nor had previous children. In conclusion, exome sequencing is indicated when detecting the above-mentioned signs. Prenatal diagnosis of IDH1 loss can help parents and healthcare providers to make informed decisions regarding pregnancy. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.