Mild L afora disease: Clinical, neurophysiologic, and genetic findings

• Published in: Epilepsia (Copenhagen) 2014-12, Vol.55 (12)
• Main Authors: Ferlazzo, Edoardo, Canafoglia, Laura, Michelucci, Roberto, Gambardella, Antonio, Gennaro, Elena, Pasini, Elena, Riguzzi, Patrizia, Plasmati, Rosaria, Volpi, Lilia, Labate, Angelo, Gasparini, Sara, Villani, Flavio, Casazza, Marina, Viri, Maurizio, Zara, Federico, Minassian, Berge A., Turnbull, Julie, Serratosa, Jose M., Guerrero‐López, Rosa, Franceschetti, Silvana, Aguglia, Umberto
• Format: Article
• Language: English
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/epi.12806

We report clinical, neurophysiologic, and genetic features of an Italian series of patients with Lafora disease ( LD ) to identify distinguishing features of those with a slowly progressive course. Twenty‐three patients with LD (17 female; 6 male) were recruited. Mean age (± SD) at the disease onset was 14.5 ± 3.9 years and mean follow‐up duration was 13.2 ± 8.0 years. NHLRC 1 mutations were detected in 18 patients; EPM 2A mutations were identified in 5. Patients who maintained >10 years gait autonomy were labeled as “mild” and were compared with the remaining LD patients with a typical course. Six of 23 patients were mild and presented significantly delay in the age at onset, lower neurologic disability score at 4 years after the onset, less severe seizure phenotype, lower probability of showing both photoparoxysmal response on electroencephalography ( EEG ) and giant somatosensory evoked potentials, as compared to patients with typical LD . However, in both mild and typical LD patients, EEG showed disorganization of background activity and frequent epileptiform abnormalities. Mild LD patients had NHLRC 1 mutations and five of six carried homozygous or compound heterozygous D146N mutation. This mutation was found in none of the patients with typical LD . The occurrence of specific NHLRC 1 mutations in patients with mild LD should be taken into account in clinical practice for appropriate management and counseling.