Absence seizures with intellectual disability as a phenotype of the 15q13.3 microdeletion syndrome

Abstract

15q13.3 microdeletions are the most common genetic findings identified in idiopathic generalized epilepsies to date, and they are present in up to 1% of patients. In addition, 15q13.3 microdeletions have been described in patients with epilepsy as part of a complex neurodevelopmental phenotype. We analyzed a cohort of 570 patients with various pediatric epilepsies for 15q13.3 microdeletions. Screening was performed using quantitative polymerase chain reaction; deletions were confirmed by array comparative genomic hybridization (CGH). We carried out detailed phenotyping of deletion carriers. In total, we identified four pediatric patients with 15q13.3 microdeletions, including one previously described patient. Two of four deletions were de novo, one deletion was inherited from an unaffected parent, and for one patient the inheritance is unknown. All four patients had absence epilepsy with various degrees of intellectual disability. We suggest that absence epilepsy accompanied by intellectual disability may represent a common phenotype of the 15q13.3 microdeletion in pediatric patients with epilepsy.

Figure 1

EEG recordings of 15q13.3 microdeletion carriers. (A) Bilateral synchronous regular 3-Hz spike-wave discharges in proband 1 lasting for 15 s associated with clinical absence seizures. (B) Absence seizure in proband 2 lasting for 4 s. (C) Spike-wave discharges lasting for 3 s in proband 4. This proband was affected by absence status lasting for >6 h.

Figure 2

Pedigrees of 15q13.3 microdeletion carriers. All four probands (marked by the arrow) are affected by absence seizures and intellectual disability. Additional microdeletion carriers (family of proband 1) are marked by an asterisk. No deletions (“no del”) were found in several relatives investigated by array-CGH.