Rationale: Mutations in the gene encoding protocadherin-19 (PCDH19) cause developmental and epileptic encephalopathy. It is an X-linked disorder characterized by infantile onset clustered and fever-induced seizures, often associated with intellectual disability and autistic features.
This disorder affects heterozygous females and somatic mosaic males, while hemizygous males are unaffected.
It has been proposed that PCDH19 mosaicism might affect cell-cell communication, according to the cellular interference hypothesis. Disrupted synaptic function and neuronal connectivity is an important pathophysiology. However, how PCDH19 mosaic expression affects neuronal network activity is unknown. This study aimed to investigate EEG connectivity in patients with PCDH19-related epilepsy. Methods: We collected 63 serial EEGs from 12 patients with PCDH19-related epilepsy. EEGs were recorded according to the international 10-20 system. Resting-state sleep EEG data were collected and artifacts were removed. We evaluated the default mode network (DMN) of 28 regions and small-world networks. Small-world networks were calculated by clustering coefficient (Cp)/path length (Lp).
Results: Overall, high DMN network strengths were observed in the delta, theta, and alpha bands. There were no definite high DMN network strengths in higher frequency bands: beta and gamma. Among the delta, theta, and alpha, alpha DMN connectivity was dominant. Small-world networks were increased in the alpha band and decreased in the delta and theta band.
Conclusions: Functional hyperconnectivity in alpha frequency was observed in the patients with PCDH19-related epilepsy. It suggests that PCDH19-related epilepsy has characteristic abnormal neuronal connectivity features. These results provide valuable information about the pathophysiology of PCDH19-related epilepsy and can be applied as a biomarker.
Funding: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government, Ministry of Science and ICT (MSIT) (No. 1711191558).