Genetics and Inflammation: New Perspectives on Migraine in Childhood and Adolescence

In the clinical as well as the research context, migraine in childhood and adolescence is still an underestimated condition, despite its significant impact on participation and quality of life. In particular, distinct pathophysiological mechanisms in the young are largely unexplored. Now, Winther et al.[1] and Güzin et al.[2] shed light on the genetic and inflammatory mechanisms underlying this complex disorder in young patients, highlighting the importance of targeted research in the field.

The scoping review by Winther et al.[1] investigated the heritability of primary headaches in children and adolescents. A systematic analysis of retrospective cohort studies, twin studies, and follow-up investigations demonstrated a distinct familial aggregation, particularly for migraine. Notably, the studies indicated that children with a positive family history not only have a higher risk of developing migraine but also tend to experience an earlier onset and more severe pain. Moreover, a considerable proportion of patients underwent changes in their headache diagnosis over time, suggesting complex interactions between genetic, epigenetic, and environmental factors. This presents a major challenge for personalized therapeutic approaches and necessitates further research into the prognosis and prevention of migraine.

Complementing this, the study by Güzin et al.[2] examined the prevalence of migraine in children with Familial Mediterranean Fever (FMF), an autoinflammatory disorder due to pathogenic variants in the MEFV gene. The authors found a high prevalence of migraine in this patient cohort, particularly but not statistically significant in relation to the prevalence of the M694V and E148Q variants. This suggests an interplay between inflammatory pathways and genetic predispositions and should prompt a standardized assessment for primary headaches in children with FMF.

Both studies highlight the increasing insights into the complex pathophysiological mechanisms underlying migraine, which should not be regarded as a simple pain disorder. This opens new research avenues to improved diagnostics and holds potential for the development of innovative, personalized treatment strategies.

As pediatric neurologists, we are called upon to translate these insights into clinical practice, improving the care of affected children and adolescents. The present studies mark an important step in this direction and should foster further research in this field.

Publication History

Article published online:
12 May 2025

• References

• 1 Winther CCH, Berring-Uldum AA, Debes NM. Inheritance of primary headache in children and adolescents-A scoping review. Neuropediatrics 2025; 56: 152-159
• 2 Güzin Y, Dağdaş SM, Sarıkaya Uzan G. et al. The prevalence of migraine in children diagnosed with Familial Mediterranean Fever. Neuropediatrics 2025; 56: 194-199