EP05.61: Expanding the KIDINS220/ARMS phenotype: heterozygous variant with fetal complex CNS anomaly

Following termination of pregnancy due to multiple brain malformations a non-consanguineous couple of Jewish descent sought genetic counselling. The brain malformations included corpus callosum dysgenesis, abnormal brain stem morphology, abnormal cortical sulcation and hypertelorism. Trio exome sequencing revealed heterozygous de-novo likely pathogenic variant in KIDINS220 gene. KIDINS220 encodes for a 220-kD scaffolding protein, also referred to as ankyrin repeat-rich membrane spanning (ARMS) protein. Predominantly found in the brain and neuroendocrine cells, this protein is believed to have a crucial role in embryonic neuronal differentiation, and the maturation of axonal/dendritic processes. Heterozygous variants in KIDINS220, have been linked to spastic paraplegia, intellectual disability, nystagmus, and obesity syndrome (SINO). Reports on prenatal findings are limited and primarily consist of isolated cases of ventriculomegaly. This report expands the prenatal phenotype. Our report highlights the importance of additional investigations in cases of non-isolated ventriculomegaly. The neurosonogram identified significant additional anomalies prompting exome sequencing, which is not indicated in most cases of fetal ventriculomegaly.