Miller-Dieker Syndrome: Genetic Etiology, Neurocognitive Impact, and Clinical Implications in a Neuronal Migration Disorder

Miller-Dieker Syndrome (MDS) is a rare neurodevelopmental disorder caused by a deletion on chromosome 17p13.3, notably affecting the PAFAH1B1 (LIS1) gene. This genetic alteration disrupts neuronal migration, resulting in type I lissencephaly and profound neurocognitive impairments. To critically analyze the genetic basis and neurocognitive profile associated with MDS and examine its clinical relevance through a systematic literature review. A descriptive and retrospective literature review was conducted following PRISMA guidelines. Searches were conducted across major scientific databases using terms using terms such as "Miller-DiekerSyndrome," "neuronal migration disorder," "genetic deletion 17p13.3," and "neurocognition." Studies reviewed consistently associate the 17p13.3 deletion with pathogenic variants in PAFAH1B1, YWHAE, RELN, and ARX. These genes are critical for neuronal migration and brain cortical structure. Although the clinical profiles were not uniformly described, the literature supports links between these genetic pathogenic variants and developmental delay, epilepsy, and intellectual disability. Neuroimaging is a fundamental tool for the diagnosis and structural characterization of MDS. However, this review primarily focused on the genetic and neurocognitive dimensions. While some studies mentioned imaging findings, detailed neuroanatomical data were not systematically or consistently reported across the literature, which limited their inclusion in the comparative analysis presented in this manuscript. MDS exemplifies a severe genetic disorder of neuronal migration. Genetic and neurocognitive evaluation is key for early diagnosis and management. Future research should focus on integrative neurodevelopmental models and potential molecular therapies.