10p11.2 Deletion

Okamoto et al. “A Patient With Intellectual Disability, Agenesis of Corpus
Callosum, and Congenital Heart Disease Associated With Chromosome 10p11.2 Microdeletion”. “American Journal of Pediatrics Part A” 2026, v. 0:1–8

DeSanto–Shinawi syndrome (WAC-related disorder) is a 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. There are some reports of individuals with large chromosomal deletions at this genomic region that exclude the WAC gene. Okamoto et al. present on a patient with a 4.2 Mb microdeletion at chromosome 10p11.23p11.21 to explore the phenotypic picture of proximal chromosome 10p deletions independent of WAC haploinsufficiency. In infancy, the proband was diagnosed with a congenital heart defect and significant atrophy of his left testis. He presented with dysmorphic features including hypertelorism, down-slanted palpebral fissures, a depressed nasal bridge, short nose, short philtrum, full cheeks, and downturned corners of the mouth. He was later observed to have developmental delays (he learned to walk at 2 years old) and growth hormone deficiency (he subsequently received growth hormone therapy). A brain MRI confirmed complete agenesis of the corpus callosum (ACC). He was in special education classes throughout his childhood and adolescence. At 30 years old, he presented with short stature and was severely obese. An ophthalmologic examination revealed astigmatism, hyperopia, and amblyopia. A chromosomal microarray analysis revealed a microdeletion on chromosome 10 that included the following genes ZNF438, ZEB1, ARHGAP12, KIF5B, EPC1, CCDC7, ITGB1, NRP1, and PARD3. Among these, only ZEB1 is established to be disease-causing gene. Based on the authors’ literature review, ZEB1 is suggested to play a role in the development of ACC and ophthalmologic problems such as corneal dystrophy. One paper showed nine individuals with ZEB1 loss-of-function variants and ACC who all had normal intellect. Thus, Okamoto et al. suggest that the loss of EPC1 and/or KIF5B is related to the intellectual disability observed in the current patient. They also suggest that loss of NRP1 could be attributed to the congenital heart defects observed in the current patient. Ultimately, additional information is necessary to better characterize the genotype-phenotype of these genes in proximal 10p11.2 deletions when the loss of WAC is excluded.

Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. Review and formatting by Nicole Talaba, MS CGC. For more information on any article please contact info@chromodisorder.org