Migraine phenotype in patients with a dual versus single parent history

Dear Editor,

We read with great interest the recent study by Eidlitz-Markus et al. in which they report an association between family history of migraine and age of onset in a tertiary pediatric headache clinic (1). The authors identified an earlier age of onset when either one or both parents were affected as compared to neither. A statistical difference could not be detected in age of onset when individuals with one versus two parent involvement were compared, with a small sample size of the latter group being a study limitation. We recently investigated a similar hypothesis, that dual versus single parent migraine history would be associated with greater phenotypic complexity, with access to a larger cohort (2). We retrospectively analyzed cohort data from the Mayo Clinic Headache Registry, including a total of 1119 patients diagnosed with migraine according to International Classification of Headache Disorders criteria, having a family history of migraine in either one parent (n = 953), or both (n = 166). We included only individuals who reported an age of onset prior to age 16 in order to enrich our cohort to include those more likely to have a heritable component (3). In our study, we also found no difference in age of onset between those with a single versus dual parent migraine history (Table 1). We identified depression comorbidity and greater migraine-related disability among individuals with a dual parent history, but no other phenotypic differences (e.g. presence of aura or menstrual migraine). Of note, sub-group analysis of those with a single parent history revealed a slightly earlier median age of onset among those with a paternal (11 years, interquartile range (IQR): 8–13) versus maternal (12 years, IQR: 9–13) history (p = 0.0013). We concluded that in contrast to our study hypothesis, many basic phenotypic features of migraine were not more prevalent among those with a dual versus single parent migraine history.

Table 1.

Association of migraine phenotype with single versus dual parent migraine history.

	Single parent (n = 953)	Dual parent (n = 166)	p value
Gender, % female	82.48	77.11	0.0990
Age of onset, median (range)	12 (1–15)	12 (2–15)	0.2559
Aura, %	45.96	50.00	0.3356
Menstrually related migraine, %	61.35	57.41	0.4370
Comorbidity: anxiety, %	17.75	16.87	0.7825
Comorbidity: depression, %	17.96	24.70	0.0410
MIDAS score, median (range)	25 (0–450)	33 (0–400)	0.0067
Headache days over three months, median (range)	30 (0–92)	36 (0–92)	0.1508
Avg. headache intensity over prior three months, median (range)	7 (0–10)	7 (0–10)	0.4877

MIDAS: migraine disability assessment.

Our studies had a similar approach, involving analysis of tertiary headache clinic database records, with the main differences being analysis of pediatric versus adult clinic data, and the sample size. One would hypothesize that Eidlitz-Markus et al. would have more valid data regarding age of onset given the pediatric population, with our study having greater statistical power given the much larger sample size. Specifically, Eidlitz-Markus et al. analyzed data from only 15 cases with both parents having migraine, versus 166 in our sample. Similar to our study, Eidlitz-Markus et al. did not identify many significant phenotypic differences between those with one versus two parent histories.

Migraine is a heterogeneous disorder, with complex, polygenic contributions to disease susceptibility. While familial factors account for up to 50% of the risk of migraine, relatively little is known about the role of genetics in influencing migraine phenotype. A minority of studies have suggested specific genetic contributions to phenotypic subtypes (e.g. menstrual migraine). Future studies may prospectively address this question, which has implications for understanding the emerging complex genotype-phenotype relationships in migraine patients.