Purpose of review: To highlight recent genetic findings in migraine and discuss, new mutations in hemiplegic migraine genes in familial and sporadic cases and relevant candidate gene association studies. Special attention will be given to comorbid diseases of migraine.
Recent findings: Familial hemiplegic migraine (FHM) is genetically heterogeneous with mutations in the CACNA1A (FHM1), ATP1A2 (FHM2) and SCN1A (FHM3) genes. Nineteen novel ATP1A2 mutations were identified last year, eleven of them in FHM2 families. A systematic genetic analysis of patients with sporadic hemiplegic migraine revealed five mutations in this gene, which has implications for genetic counselling. The identification of a second FHM3 SCN1A mutation definitely established SCN1A as a migraine gene. The identification of TREX1 mutations in families with retinal vasculopathy and associated diseases such as migraine may provide new insights in migraine pathophysiology.
Summary: Many novel ATP1A2 mutations were identified in patients with familial and sporadic hemiplegic migraine. In sporadic patients, ATP1A2 screening has the highest chance of finding a causal mutation. A second FHM3 mutation definitely established the epilepsy SCN1A gene as a migraine gene. The discovery of genes in monogenic diseases in which migraine is prominent may lead to new insights in the molecular pathways involved in migraine pathophysiology.