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Monozygous twins discordant for epilepsy

In their interesting contribution, Briellman and colleagues recently reported on 12 monozygotic twins with discordance for epilepsy. In 4 of the patients, magnetic resonance imaging disclosed overt developmental abnormalities. Three had malformations of cortical development (MCDs) (closed-lip schizencephaly, focal cortical dysplasia and bilateral periventricular heterotopias) and one had septooptico dysplasia. The most likely explanation for the discordance was thought to be either a postfertilization somatic mutation in genes critical for cortical development, or an unrecognized early environmental insult; alternatively a random developmental event. However, the mechanism may not be so enigmatic. Several cases of MCDs in only one of monozygotic twins have been documented. Discordance for the congenital perisylvian syndrome, bilateral occipital polymicrogyria, and periventricular nodular hetereotopias, as well as a a gray matter heterotopion, have been reported. We have recently published a similar case, raising the question: Is monochorionic twinning a risk factor for focal cortical dysgenesis? Discordance of MCDs in monozygotic twins sheds light on the importance of acquired, and in particular vascular factors in the pathogenesis of these disorders. In monozygotic twins, a single placenta with vascular connections is common. The feto-fetal transfusion syndrome has increasingly been recognized in obstetrical literature with the expanding use of ultrasound. In the classical form, the donor dies in utero, but both infants may survive with or without damage. White matter infarcts and developmental abnormalities have been reported in the brains of such children. Diverse situations may lead to a large spectrum of clinical patterns. This mechanism may also play a role in born singletons with cerebral developmental disorders. Bilateral parietal as well as perisylvian polymicrogyria have previously been associated with the documented early death of a co-twin. With the increasing use of ultrasonography in early pregnancy, it has been demonstrated that a surprisingly large proportion of pregnancies start out as duplicate products. In one series, the “vanishing twin” phenomenon was found in up to 20% of pregnancies. We hypothesize that a proportion of cases with malformations of cortical development with obscure cause is the result of a “vanishing twin” causing transient hemodynamic disturbances in the survivor. The role of this mechanism in the genesis of malformations of cortical development can only be truly assessed by large-scale, prospective, ultrasound studies in early pregnancy.