Parental age and the occurrence of sporadic brain arteriovenous malformations

Abstract

Parental age and the occurrence of sporadic brain arteriovenous malformationsDear editor,The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unclear, but accumulating evidence suggests a genetic susceptibility.1 Within the context of genetic susceptibility, de novo mutations arising from the germline may play a role. As parental ageing is a risk factor for transmission of de novo mutations, 2,3 we investigated whether higher parental age at delivery is associated with the occurrence of BAVMs in the offspring.We approached a cohort of 682 BAVM patients, who were seen between 1990 and 2006 at one of four university hospitals in the Netherlands, with a postal questionnaire to retrieve the dates of birth of their parents. 4 We compared parental age at delivery of patients with a BAVM, with population means of parental age matched for sex, birth order, and year of birth using the Mann-Whitney U test.5 Because maternal age of the controls for patients born before 1950 was lacking, we extrapolated data from more recent years, and performed a sensitivity analysis excluding this subgroup to address the potential influence on the results. Paternal age of the control population was unavailable before 1996. 5 Based on available data on the period after 1995, 5 we assumed that fathers were on average three years older than mothers.We obtained responses from 460 (67%) patients. 4Baseline characteristics, including the year of birth, did not differ between responders and non-responders. We found no significant difference in both maternal and paternal age at the time of delivery between BAVM patients and the matched control population (Table 1). In addition, the sensitivity analysis excluding the patients born before 1950, yielded essentially the same results.In conclusion, parental age at delivery did not differ between patients with a BAVM and the general population. Our results do not support the hypothesis that de novo mutations arising from the germline underlie BAVM pathogenesis.