Hypersynchronous EEG Patterns in a Patient with Holoprosencephaly

Holoprosencephaly is a congenital malformation of the central nervous system resulting from failure of the rostral neural tube to bifurcate into the two cerebral hemispheres. Deep brain structures including the thalamus, hypothalamus, and basal ganglia can also be affected to varying degrees. Here we present a patient with a rare de novo pathogenic variant in the PPP1R12A gene and the middle interhemispheric (MIH) variant of holoprosencephaly with hypersynchronous patterns on electroencephalography (EEG). The most prevalent abnormal pattern was abundant hypersynchronous rhythmic theta activity most prominent over the bilateral centro-parietal regions. There was also frequent hypersynchronous rhythmic beta activity and rhythmic alpha range activity, which occurred both synchronously and asynchronously. Finally, there were occasional periods of voltage attenuation interrupting hypersynchronous theta activity. While hypersynchronous theta activity and episodic attenuation have been previously described in alobar and semilobar variants of holoprosencephaly, our report is the first to describe these findings in a patient with the MIH variant as well as the first to describe EEG patterns in a patient with a pathogenic variant in the PPP1R12A gene mutations in which are associated with urogenital and/or brain malformation syndrome. Additionally, the hypersynchronous alpha activity is the first report of such an EEG pattern in holoprosencephaly. In order to develop a more complete understanding of EEG patterns in holoprosencephaly further study is needed but this is challenged by the relative rarity of the disease.