Case report: ZNF526-related Dentici-Novelli neurodevelopmental syndrome in two sibling

Abstract

Background: ZNF526 has been recently identified as a gene associated with Dentici-Novelli neurodevelopmental syndrome (DENNED), an autosomal recessive disorder characterized by global developmental delay, microcephaly, cataracts, and epilepsy. It very rarely happens in the East Asian population with only 3 cases currently.

Case presentation: In this case report, we present two sibling patients from China with a novel compound heterozygous variant (c.1512_1513del and c.1501C>A) in the ZNF526 gene (NM_133444.3), expanding the phenotypic and geographic spectrum of DENNED. One patient's cranial MRI revealed widening of the extracerebral space in the bilateral frontotemporal region, abnormal EEG patterns, slow awake background activity, poor sleep background, and indistinguishable sleep cycles, which was never reported before. Our report also marks the first documentation of DENNED with this new ZNF526 heterozygous variant around the world.

Discussion: With our case, we discuss all published 9 cases of ZNF526 variants so far to enhance understanding of this rare disease and its clinical manifestations. We find that the reported DENNED in East Asia has some differences to cases in Europe and Middle East and there are some correlations between genetic variants and clinical manifestations.