Rare Xq23 Microdeletion Involving the DCX and PAK3 Genes Presenting With Lissencephaly, Agenesis of the Corpus Callosum, and Intractable Epilepsy: A Case Report

Abstract

X-linked lissencephaly spectrum disorder is a rare neurodevelopmental condition resulting from pathogenic variants that disrupt normal neuronal migration, with doublecortin (DCX) being one of the genes most frequently implicated. Similarly, pathogenic variants of the p21-activated kinase 3 (PAK3) gene are associated with X-linked syndromic intellectual disability, developmental delay, and epilepsy. Contiguous deletions involving both genes are exceedingly uncommon and may present with a complex neurological phenotype. We report the case of a seven-month-old male with intellectual disability, global developmental delay, intractable epilepsy with generalized-onset seizures, lissencephaly, agenesis of the corpus callosum, hypertonia, hyperreflexia, gastroesophageal reflux, and constipation. Brain magnetic resonance imaging (MRI) demonstrated structural brain abnormalities, while whole exome sequencing (WES) with copy number variant (CNV) analysis identified a pathogenic hemizygous 258-kb deletion at Xq23 (110395597_110654202)x0), encompassing the DCX gene and partially involving the PAK3 gene. This report aims to expand the current limited understanding of the clinical manifestations associated with Xq23 microdeletions involving DCX and PAK3. It also highlights the importance of advanced genetic testing in children presenting with developmental delay, epilepsy, and structural brain abnormalities, allowing for early diagnosis, appropriate genetic counseling, and, ultimately, improved patient care.