KBG syndrome: A scoping review of electroclinical features of patients with epilepsy

KBG syndrome is a rare autosomal developmental disorder caused by pathogenic variants of the ANKRD11 gene. This scoping review aimed to explore all current literature data regarding clinical and electroencephalographic features of patients with KBG syndrome and epilepsy.

We conducted a literature review of previously published cases of patients with KBG syndrome and epilepsy in PubMed, Scopus, and Web of Science databases in English, focusing on seizure semiology and electroencephalographic features.

Fifty-four studies were included in the review, including 233 patients with KBG syndrome and epilepsy. Most children with KBG syndrome and epilepsy (89.7%) had developmental delay and intellectual disability. The most common neurological symptoms were hypotonia (30.7%), sleep disturbances (20%), ataxia (18.7%), migraine (8.3%), and stereotypies (6.7%) (N = 75, available data on neurological symptoms). The median age of developing seizures was 4 years (range 1 month-51 years). Patients with KBG syndrome had most commonly generalized seizures (73.9%), although focal seizures occurred in 37.9% of cases (N = 140, available data on seizure type). Generalized tonic-clonic seizures were the most common seizure type (38.2%), followed by absences (26.6%), and focal seizures with or without preserved consciousness (21.9% and 19.1%, respectively). Interictal EEG showed focal and, less frequently, generalized discharges (24.6% vs. 15%) in the 118 patients with available EEG data. Almost 70% of patients were seizure-free after a mean follow-up of 9.9 years, while drug-resistant epilepsy was reported in 22.6% of cases. Patients with focal impaired consciousness seizures had significantly lower odds of achieving seizure freedom.

Epileptic seizures in patients with KBG syndrome are usually generalized and have an onset between infancy and mid-teens. Common epileptological features in KBG syndrome comprise the good response to antiseizure medication and, in most cases, the remitting nature of epilepsy. Drug-resistant epilepsy can be observed in up to one-third of cases.