Diagnostic pitfalls in patients with malformations of cortical development

Abstract

Malformations of cortical development (MCDs) are a major source of morbidity and mortality in the pediatric patient cohort. Correct diagnosis of the cause is essential for symptom management, disease prognosis and family counselling but is frequently hampered due to numerous potential pitfalls in the diagnostic process. This review highlights potential problems that either prevent the establishment of a diagnosis or are the sources of diagnostic errors. The focus is placed on hereditary causes of MCDs and strategies will be proposed to circumvent potential diagnostic pitfalls. Errors may occur during variant detection, filtering, or interpretation in relation to patient’s phenotype. Based on detailed clinical assessment suitable targeted and untargeted methods to identify pathogenic variants with context-dependent filtering and evaluation approaches will be discussed.