title: Mild Lafora disease: clinical, neurophysiologic, and genetic findings.
abstract: 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. NHLRC1 mutations were detected in 18 patients; EPM2A 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 NHLRC1 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 NHLRC1 mutations in patients with mild LD should be taken into account in clinical practice for appropriate management and counseling.
authors.affiliation: Magna Graecia University of Catanzaro, Catanzaro, Italy; Regional Epilepsy Center, Bianchi-Melacrino-Morelli Hospital, Reggio Calabria, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Ferlazzo
authors.forename: Laura
authors.initials: L
authors.lastname: Canafoglia
authors.forename: Roberto
authors.initials: R
authors.lastname: Michelucci
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambardella
authors.forename: Elena
authors.initials: E
authors.lastname: Gennaro
authors.forename: Elena
authors.initials: E
authors.lastname: Pasini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Riguzzi
authors.forename: Rosaria
authors.initials: R
authors.lastname: Plasmati
authors.forename: Lilia
authors.initials: L
authors.lastname: Volpi
authors.forename: Angelo
authors.initials: A
authors.lastname: Labate
authors.forename: Sara
authors.initials: S
authors.lastname: Gasparini
authors.forename: Flavio
authors.initials: F
authors.lastname: Villani
authors.forename: Marina
authors.initials: M
authors.lastname: Casazza
authors.forename: Maurizio
authors.initials: M
authors.lastname: Viri
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Berge A
authors.initials: BA
authors.lastname: Minassian
authors.forename: Julie
authors.initials: J
authors.lastname: Turnbull
authors.forename: Jose M
authors.initials: JM
authors.lastname: Serratosa
authors.forename: Rosa
authors.initials: R
authors.lastname: Guerrero-López
authors.forename: Silvana
authors.initials: S
authors.lastname: Franceschetti
authors.forename: Umberto
authors.initials: U
authors.lastname: Aguglia
mesh_terms: D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007558:Italy; D020192:Lafora Disease / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; C478960:NHLRC1 protein, human; D044767:Ubiquitin-Protein Ligases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C114990:EPM2A protein, human
keywords: Dementia; EEG; Mild; Progressive myoclonus epilepsy; Slowly progressive