Refractory epilepsy and regression in a patient with a de novo heterozygous POGZ mutation

Mutations in the pogo transposable element with zinc finger domain（POGZ）gene are associated with autism spectrum disorder （ASD）and intellectual disability. A total of 40 cases have been reported, and their clinical features include severe phenotypes such as severe speech and language delay, vision problems, microcephaly, and a predisposition towards obesity. Although 20% of these cases showed EEG abnormalities, epilepsy has not been reported. We present the case of a patient with refractory epilepsy and regression in which whole exome sequencing identified a de novo heterozygous POGZ mutation（c.2102del;p.Pro701Leufs ^＊ 18）. He was diagnosed with autism spectrum disorder at 6 years of age. From 7 years and 8 months of age, he experienced epileptic seizures that involved falling backwards, head nodding and ocular deviation. An EEG showed a spike-and-slow-wave at F3 and F4. He was diagnosed with frontal lobe epilepsy, and treated with various anti-epileptic drugs （e.g. CZP, VPA, CLB, PHT, LTG, PB, CBZ and LEV）, which eventually reduced his epileptic seizures from over 10 to 2-3 times per day. Moreover, this patient had repetitive aspiration pneumonia from 14 years of age, necessitating a tracheotomy and laryngo-tracheal separation. Phenotypes associated with a POGZ mutation might, therefore, have a wider spectrum than previously recognized, and include not only ASD, but various neurological problems such as progressive epilepsy syndrome.