Language deficits in GRIN2A mutations and Landau–Kleffner syndrome as neural dysrhythmias

Abstract

We review epilepsy-related aphasias in connection with GRIN2A mutations, focusing on acquired childhood epileptic aphasias such as Landau-Kleffner syndrome (LKS). The spontaneous speech of children with LKS exhibits syntactically simplified utterances, severe word finding difficulties, and severe phonological paraphasias. Characterizing LKS as a neural dysrhythmia, we review how EEG abnormalities typically manifested during non-rapid eye movement (NREM) sleep as electrical status epilepticus are related to sleeping disorders partly caused by GRIN2A mutations. Expanding on speculations originally put forward by Landau & Kleffner, 1957, we explore how neural processes such as sharp-wave ripples, sleep spindles, slow oscillations, and their cross-frequency couplings are necessary for language-related processes which are perturbed in LKS, accounting in part for the linguistic profile of epileptic aphasias.