INTRODUCTIONEpilepsy is a common neurological disorder affecting more than 70 million people around the world. It is the most common neurological disorder in the pediatric population, affecting 1% to 3% of children, and is defined as any disorder in which spontaneous recurrence of unprovoked seizures is the main symptom. A seizure is usually defined as a sudden alteration of behavior due to a temporary change in the electrical functioning of the brain, that continuously generates tiny electrical impulses in an orderly pattern. The etiology of epilepsy can be different, including structural, genetic, infectious, metabolic, and immune causes, but most often the cause is unknown, that is when it refers to the so-called idiopathic epilepsy, which occurs in 40% of people with epilepsy. Despite the recent introduction of new antiepileptic drugs (AEDs), about one-third of epilepsy patients have drug-resistant (refractory) epilepsy, affecting about 30% of children with epilepsy.Refractory epilepsy, which is the most severe form of epilepsy, according to the International league against epilepsy (ILAE), is defined as failure to control seizures when using two or more appropriately chosen and tolerated antiepileptic drugs (as monotherapy or in combination) during an appropriate period. Severe and refractory epilepsies in children affect their cognitive function, leading to worsening of the prognosis, serious psychosocial consequences, difficulties in care and quality of life, anxiety in the family, as well as an increase in the risk of death, including unexpected death in epilepsy (SUDEP).The expansion of genetic research and technologies in recent years and the advances in next-generation sequencing (NGS) have shown that a large proportion of unexplained epilepsies, especially idiopathic ones, have a genetic basis. Numerous epilepsy genes helped the understanding of mechanisms underlying epileptogenesis and guided the development of treatments.ANKRD11 gene functions as a co-regulator in the developing brain. The role of the ANKRD11 gene in neurodevelopment was suggested by subsequent reports of individuals with intellectual disability, facial dysmorphism, and ASD. In 1975, Herrman et al., first described the KBG syndrome, a neurodevelopmental autosomal dominant disorder, caused by the haploinsufficiency of the ANKRD11 at 16q24.3 locus due to heterozygous pathogenic variants or chromosomal imbalances/rearrangement such as point mutations, duplications or microdeletions involving this gene.KBGS is characterized by global developmental delay (DD), intellectual disability (ID), learning difficulties, neurobehavioral problems, short stature, macrodontia, facial dysmorphism, skeletal anomalies, and multiple congenital anomalies, sometimes associated with seizures, delayed closing of fontanels and electroencephalographic (EEG) abnormalities. So far, there have been reported more than 200 cases of KBG syndrome.The diagnosis of KBG syndrome is established, by the most commonly used criteria of Skjei et al. and Low et al . A diagnosis of epilepsy, a major criterion, according to Skjei et al ., and a minor criterion according to Low et al . has been reported in approximately 30% of patients in a systematic review of 140 patients with KBG syndrome. The onset of epilepsy is predominantly between infancy and mid-teens and seizure remission occurred in the majority after adolescence with good response to AEDs. Heterogeneous seizure types have been reported, with tonic–clonic seizures, absences, myoclonic seizures, and unclassified sleep-related seizures with motor symptoms being most common, but no specific epilepsy syndrome has been identified.Detailed classification of the seizures, epilepsy type, or syndrome was only made in 26 patients from 12 studies. Only two patients had an epilepsy syndrome classification. No genotype–phenotype correlation studies have been performed for the presence and type of epilepsy in patients with KBG syndrome. Generalized epilepsy with febrile seizures plus (GEFS+) is reported in a de novo mutation of the ANKRD11gene, with a clinical phenotype compatible with KBG syndrome.A systemic review of epilepsy and EEG anomalies in subjects with KBG syndrome is deficient. Samanta first described in a patient an intermittent bisynchronous temporo-occipital rhythmic delta activity and episodes of staring spells with no EEG changes suggesting that these findings may be specific to KBG syndrome. Here, we report a patient with a severe neurological phenotype of KBG syndrome associated with a novel heterozygous frame-shift de novo variant in the ANKRD11 gene, to contribute to identifying a specific electroclinical pattern of KBG syndrome.