X-LINKED SPLICEOSOME GENE GPKOW MUTATION ASSOCIATED WITH SMALL HEAD, SMALL SIZE, AND MILD SPEECH DELAY IN A 4 YEAR OLD CHILD.

Abstract

The protein product of the X-linked gene GPKOW is a fundamental element of pre- mRNA splicing within a cellular structure called the spliceosome, important in the synthesis of the body’s proteins. 1 A single case report linked a GPKOW defect with fetal demise and severe small head size in 2014, 2 and recently 3 more severely affected cases have been described. 3 Here we describe a young boy with a likely pathologic GPKOW genetic variant and an apparently normal head size in utero, a small head size at birth, and a progressively smaller head size with time. He was mildly small size at birth and fell below the normal growth curve by 2 months of age. An early motor delay was mild and resolved after a year of age, and his attention span, sociability, and early language skills did not indicate developmental delay. His mother, a carrier of the gene, has a small head size, mild short stature, and absent any neurologic issues. GPKOW is an important gene for brain and body growth, and male patients with less impactful variants in the gene may thrive and demonstrate mild and not severe outcomes.