A Case Report of PLXNA1-Related Dworschak-Punetha Neurodevelopmental Disorder With Pachygyria and Polymicrogyria

Plexin-A1 is involved in axonal guidance in the developing human brain. Variants in the PLXNA1 gene are associated with a neurodevelopmental disorder characterized by early-onset epilepsy, intellectual disability, syndromic features, and brain and eye anomalies. We report a 19-month-old boy who presented with global developmental delay, right-sided ptosis, and a growth pattern above the expected range. Malformations of cortical development in the form of focal pachygyria and polymicrogyria were also observed. Cytogenetic microarray and trio whole-exome sequencing done in 2020 failed to detect any candidate variants. On re-analysis of the exome in 2025, we detected a novel homozygous splice site variant in PLXNA1:c.4870+1G>A. This variant is predicted to cause aberrant splicing and premature truncation of the protein. The clinical features of pachygyria with polymicrogyria and growth pattern above the expected range are novel and contribute to the growing phenotypic spectrum of PLXNA1-related neurodevelopmental disorders.