Pediatric migraine: Neurodevelopmental mechanisms, clinical phenotypes, and modern therapeutics

Figure 1 Genetic susceptibility and developmental modulation in pediatric migraine. Pediatric migraine arises from a spectrum of genetic mechanisms that interact dynamically with brain development. A: Rare monogenic forms, such as familial hemiplegic migraine, demonstrate how ion channel and transporter dysfunction (CACNA1A, ATP1A2, SCN1A) lead to neuronal hyperexcitability and a reduced threshold for cortical spreading depression; B: In most children, migraine reflects a polygenic architecture, with multiple common variants collectively influencing synaptic transmission, neurovascular signaling, and cortical excitability; C: Developmental and environmental modifiers, including pubertal hormonal changes, epigenetic regulation, sleep disruption, and psychosocial stress, interact with genetic vulnerability to trigger clinical migraine expression across childhood and adolescence.