A novel pathogenic heterozygous mutation in the CDC42BPB gene: a case report of global developmental delay potentially associated with Chilton-Okur-Chung syndrome

Abstract

Terminal deletions involving chromosome 14q32 are exceptionally rare and associated with variable neurodevelopmental phenotypes. We report a female child with fetal growth restriction, axial hypotonia, global developmental delay, delayed motor acquisition, and characteristic craniofacial dysmorphisms, including high forehead, downslanting palpebral fissures, retrognathia, sparse scalp hair, sparse eyebrows, and bilateral instep edema. Additional findings included patent ductus arteriosus, mild valvular insufficiency, and a globally thin corpus callosum on brain magnetic resonance imaging. Chromosomal microarray analysis identified a de novo 4.21Mb terminal heterozygous deletion at 14q32.31q32.33 encompassing multiple clinically relevant genes, including CDC42BPB, a gene associated with Chilton-Okur-Chung neurodevelopmental syndrome (CHOCNS). The deletion was classified as pathogenic according to ACMG/AMP criteria and supported by previously reported pathogenic alterations in DECIPHER. The patient demonstrated a relatively favorable developmental trajectory following early multidisciplinary intervention, achieving independent ambulation by 36 months with progressive cognitive and language acquisition. This report expands the phenotypic spectrum associated with distal 14q32 deletions involving CDC42BPB and highlights the importance of early diagnosis, longitudinal follow-up, and multidisciplinary intervention in rare neurodevelopmental disorders.