Elena Piazza 1 Andrea Ruggieri 2 Anna Elisabetta Vaudano 2,3 Francesca Brustia 1 Umberto Balottin 1 Erika Della Mina 4 Roberto Ciccone 4 Orsetta Zuffardi 4 Pierangelo Veggiotti 1 Stefano Meletti 2,3 1 National Neurological Institute C. Mondino, Division of Child Neuropsychiatry, Department of Brain and Behavioral Sciences, University of Pavia, Italy 2 Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy 3 NOCSAE Hospital, AUSL Modena, Italy 4 Department Molecular Medicine, University of Pavia, Italy Corresponding author: Pierangelo Veggiotti National Neurological Institute C. Mondino, Division of Child Neuropsychiatry, Department of Brain and Behavioral Sciences, University of Pavia Via Mondino, 2 27100 Pavia, Italy E-mail: pveggiot@unipv.it Abstract Deletions and mutations in the GRIN2A gene, cod- ing for the a-2 subunit of the neuronal N-methyl-D- aspartate (NMDA) receptor, have been described in patients with variable phenotypes ranging from mental retardation to milder phenotypes sugges- tive of benign childhood epilepsy with centrotem- poral spikes (BECTS). We describe a multi-gener- ation family affected by focal epilepsy with a monogenic inheritance due to a GRIN2A mutation. While the EEG trait, the normal structural MRI, and the semiology of sleep-related seizures were typi- cal of BECTS, atypical features included the pres- ence of a borderline cognitive development with speech/language disorder in several of the affect- ed members. An EEG-fMRI study performed in the proband revealed that interictal spikes were relat- ed to a BOLD signal increase over the sensory- motor cortex, thus providing evidence for a local- ized dysfunction of the rolandic cortex bilaterally. KEY WORDS: rolandic epilepsy, genetic epilepsy, EEG-fMRI. Introduction Benign childhood epilepsy with centro-temporal spikes (BECTS) or rolandic epilepsy (RE) is the most common type of childhood focal epilepsy, charac- terised by distinctive interictal EEG paroxysms over the rolandic regions, age-dependent onset, and be- nign course (1). However, some patients with RE show visuo-motor, behavioural, and especially lan- guage impairments (2, 3). It is difficult to determine whether the cognitive deficits observed in BECTS patients are due to the basic brain dysfunction responsible for epilepsy itself, or to the ef- fects of the ongoing epileptic activity which in turns would affect cognitive functions. Some Authors have recently suggested that GRIN2A should now be con- sidered a crucial genetic link between different epilep- tic syndromes and speech disorders: from the atypical rolandic epilepsy with speech impairment to the more severe Landau-Kleffner Syndrome (LKS) and Electrical Status Epilepticus during Slow Sleep (ESES) (4-7). The GRIN2A gene encodes for the NR2A (GluN2A) subunit of the N-methyl-d-aspartate (NMDA) receptor, a ligand-gated ion channel that mediates excitatory neurotransmission in the brain, making it an attractive candidate to have a role in epileptogenesis (4). Here, we describe a multi-generation family affected by focal epilepsy with a monogenic inheritance and speech/language difficulties due to a GRIN2A muta- tion. In this paper we (a) characterised the electro- clinical features of several affected members and (b) described the brain networks involved in CTS genera- tion in the proband by means of simultaneous co-reg- istration of EEG and functional Magnetic Resonance Imaging (EEG-fMRI). This last study’s aim was target- ed to evaluate whether the BOLD correlates of CTS due to GRIN2A mutation differ or not from those ob- served in idiopathic, sporadic, cases of RE (8-11). Materials and methods We examined patients IV1 (proband) and III5 (proband aunt) and collected the whole family history by interviewing III3 (proband mother) and III4 (proband uncle) (Fig. 1A). Subjects II2, II5 and III1 had unspecified childhood- 44 Clinical Cases and Reviews in Epilepsy 2016; 1(1):44-50 Brief report/Clinical case Familial rolandic epilepsy due to GRIN2A mutation: clinical and EEG-fMRI features © CIC Edizioni Internazionali