Diagnostic work-up in malformations of cortical development.

Area of Science:

• Neurology
• Developmental Biology
• Medical Imaging

Background:

• Malformations of cortical development (MCDs) encompass a diverse group of disorders affecting cerebral cortex development.
• Diagnosis often relies on neuroimaging, but subtle lesions may require neuropathology for identification.
• Known subtypes include lissencephaly, heterotopia, cobblestone malformation, polymicrogyria, and dysgyria.

Purpose of the Study:

• To provide a comprehensive overview of the diagnostic approach to malformations of cortical development.
• To highlight common diagnostic pitfalls encountered in MCD assessment.
• To describe recognizable imaging phenotypes associated with specific MCD subtypes.

Main Methods:

• This narrative review synthesizes current knowledge on MCD diagnosis.
• Clinical vignettes are used to illustrate diagnostic challenges and approaches.
• Key genetic and acquired etiologies are discussed in relation to phenotypic presentation.

Main Results:

• Diagnostic challenges include identifying subtle lesions and navigating pitfalls such as somatic mosaicism and consanguinity.
• Specific imaging phenotypes are associated with conditions like tubulinopathies, lissencephaly spectrum disorders, tuberous sclerosis complex, and FLNA-related periventricular nodular heterotopia.
• Both genetic mutations and acquired factors (e.g., congenital infections) can underlie MCDs.

Conclusions:

• A systematic diagnostic approach integrating clinical, imaging, and genetic data is crucial for MCDs.
• Awareness of diagnostic pitfalls and characteristic imaging findings improves diagnostic accuracy.
• Understanding the genetic and acquired basis of MCDs is essential for accurate classification and management.