Genetic landscape of patients with atypical absence status epilepticus: A systematic review

Atypical absence status epilepticus (AASE) is a rare subtype of nonconvulsive status epilepticus (NCSE), characterized by clouding of consciousness and continuous or fluctuating epileptiform activity, generally at a frequency below 3 Hz. Only sparse literature exists on the genetic conditions associated with it. We performed a systematic review to identify the genetic diagnoses in which AASE has been described, and examined the available clinical, EEG, treatment and outcome details. The protocol was registered in PROSPERO and reporting followed PRISMA guidelines. We searched public databases for combinations of the terms: “atypical absence status epilepticus,” “status epilepticus,” “non convulsive status epilepticus,” and “gene,” “genetics,” “epileptic encephalopathy,” “developmental and epileptic encephalopathy,” “DEE.” Only original articles in English were included. We identified 34 publications reporting 97 patients with AASE and an underlying genetic condition. Most patients had a chromosomal abnormality (88%), in particular ring chromosome 20 (53% of the total patients) and Angelman syndrome caused by a 15q11–q13 deletion (31%). Seven epilepsy genes (UBE3A, CNKSR2, TRPM3, KCNH2, NEXMIF, SYNGAP1, GABRB1) were found in which a clinical and electrographic picture consistent with AASE was described. Therefore, in the context of a possible genetic diagnosis, AASE has been reported mainly in chromosomal disorders. However, this condition is likely underrecognized and underreported, particularly in monogenic epilepsies. Therefore, a deeper phenotyping and a more standardized use of classification terms would be necessary both for clinical and research purposes. Plain Language Summary: We reviewed the scientific literature to find out in which genetic conditions a rare EEG and clinical pattern, called atypical absence status epilepticus, has been described. We found that this pattern is mainly reported in patients with changes in chromosome structure, such as ring chromosome 20 and Angelman syndrome. Among single-gene (monogenic) forms of epilepsy, it has been described in association with seven genes (UBE3A, CNKSR2, TRPM3, KCNH2, NEXMIF, SYNGAP1, GABRB1). When clinicians suspect a genetic cause of epilepsy and this finding is present, they should consider checking also for chromosomal changes.