A Male Child with Infantile Epilepsy due to a Mosaic Missense Variant of PCDH19

Background: Pathogenic variants of PCDH19, located on the X-chromosome (Xq22.1), cause a rare epileptic encephalopathy with speech and development delay, seizures, behavioral and psychiatric problems. The specific underlying pathogenic mechanism is known as “cellular interference” that results in affected heterozygous females, normal hemizygous males and affected mosaic males but its functioning is not yet clear. Objectives: Reporting new cases of affected males is considered useful to a deeper insight. Subject and Method: We present the case of a three-year-old boy with early-onset seizures at 3 months of age, mild cognitive impairment, partial control of seizures with levetiracetam, normal brain imaging. Results: The patient has a mosaic pathogenic variant c.698A>G (p.Asp233Gly) in PCDH19 assessed by Next Generation Sequencing analysis. We have compared his characteristics with the genotypes and phenotypes of 34 PCDH19 mosaic males earlier reported in the literature. Finally, we have summarized today’s knowledge about phenotype-genotype correlation and pharmacological response in these patients. Conclusions: Our report confirms that the clinical picture of mosaic affected males, resembling that of females, can show a wide variability in severity of disease and underlines a stringent need to improve therapeutic approaches and to collect data on long-term follow-up.