RESEARCH REVIEW POGZ-related epilepsy: Case report and review of the literature Alessandro Ferretti 1 | Sabina Barresi 2 | Marina Trivisano 1 | Andrea Ciolfi 2 | Maria L. Dentici 2 | Francesca C. Radio 1 | Federico Vigevano 1 | Marco Tartaglia 2 | Nicola Specchio 1 1 Neurology Unit, Department of Neuroscience, Bambino Gesù Children's Hospital IRCCS, Rome, Italy 2 Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital IRCCS, Rome, Italy Correspondence Nicola Specchio, Division of Neurology, Bambino Gesù Children's Hospital, IRCCS, Rome, P.zza S. Onofrio 4, 00165 Rome, Italy. Email: nicola.specchio@opbg.net Abstract POGZ (# 614787) encodes a multidomain nuclear protein involved in transcriptional reg- ulation and its defective function has been recently associated with a syndromic neu- rodevelopmental disorder, known as White-Sutton syndrome (# 616364). While originally epileptic seizures were unreported, it seems that epilepsy represents a recur- rent feature in affected subjects. Few data, however, are available on electroclinical fea- tures of POGZ-related epilepsy. We report a 5-year-old girl with a de novo inactivating POGZ mutation with a complex neurological phenotype characterized by hypotonia, severe developmental delay, and paroxysmal epileptic and nonepileptic events. Compar- ing this patient with the previously reported nine cases exhibiting epilepsy as associated feature, we detected that epilepsy onset is mostly during infancy (1–4 years of age), with both focal and generalized seizures. EEGs reveal that epileptic abnormalities mainly are localized in the frontal regions, and seizure control might be reached with one or multiple antiepileptic drugs. Besides dysmorphic features and other comorbidities (microcephaly, intellectual disability, absent speech, sensorineural hearing loss, and autistic spectrum disorder) major brain MR features include cortical and cerebellar atrophy, delayed mye- lination, and brainstem hypoplasia. Although the small number of patients reported, we were able to delineate primary electroclinical epileptic phenotype related to POGZ muta- tions. This would be crucial for an early identification and management of the condition. KEYWORDS children, epilepsy, POGZ, White-Sutton syndrome 1 | INTRODUCTION POGZ (# 614787) is one of the most recently identified genes associ- ated with autism spectrum disorder (ASD) (Fukai et al., 2015; Hashimoto et al., 2016; Matsumura et al., 2016). It codes for a multi- domain nuclear protein involved in chromatin remodeling, chromo- some segregation, and cell cycles progression (Matsumura et al., 2016; Nozawa et al., 2010). As a transcriptional regulator, POGZ is involved in functional neuronal networks and it plays an essential role in gene expression associated with multiple cellular processes (De Rubeis et al., 2014; Stessman et al., 2016; Suliman, Ben-David, & Shifman, 2014). In most cases, POGZ disease-causing mutations have been described as truncating or disrupting the DNA-binding activity of the protein, which suggests haploinsufficiency as the mechanism of disease (Dentici et al., 2017). Besides ASD, POGZ gene has been found mutated in patients with borderline-moderate to severe intel- lectual disability (ID) and schizophrenia (Gilissen et al., 2014; Matsumura et al., 2016; Suliman et al., 2014; Tan et al., 2016). More Received: 11 March 2019 Revised: 10 May 2019 Accepted: 12 May 2019 DOI: 10.1002/ajmg.a.61206 Am J Med Genet. 2019;1–6. wileyonlinelibrary.com/journal/ajmga © 2019 Wiley Periodicals, Inc. 1