A Patient With Intellectual Disability, Agenesis of Corpus Callosum, and Congenital Heart Disease Associated With Chromosome 10p11.2 Microdeletion

DeSanto-Shinawi syndrome is a rare genetic disorder caused by pathogenic variants or deletions involving the WAC gene, located on chromosome 10p12.1, and is characterized by developmental delay, intellectual disability, and distinctive dysmorphic features. In addition to deletions encompassing WAC, several proximal deletions on chromosome 10 that exclude WAC have also been reported. Here, we describe a patient with a microdeletion of chromosome 10p11.23-p11.21 spanning approximately 4.2 Mb. The patient exhibited intellectual disability, agenesis of the corpus callosum, and congenital heart disease. The deleted region includes the following protein-coding genes: ZNF438, ZEB1, ARHGAP12, KIF5B, EPC1, CCDC7, ITGB1, NRP1, and PARD3, while WAC was preserved. Pathogenic variants or deletions of ZEB1 are known to cause corneal abnormalities and agenesis of the corpus callosum, whereas loss of NRP1 has been implicated in the pathogenesis of congenital heart disease. We therefore hypothesize that haploinsufficiency of multiple genes within the deleted region-particularly ZEB1, EPC1, KIF5B, and NRP1-may collectively contribute to the observed clinical phenotype. These findings suggest that microdeletions involving chromosome 10p11.2 are associated with a phenotype distinct from that of DeSanto-Shinawi syndrome.