PP01.12 – 2602: Differential diagnosis of progressive myoclonic epilepsia: Five patients with Lafora disease

Abstract

Objective Lafora disease (LD) is a rare, fatal, autosomal recessive hereditary disease characterized by epilepsy, myoclonus and progressive neurological deterioration. Diagnosis is made by polyglucosan inclusion bodies (Lafora bodies) shown in skin biopsy. Responsible mutations involves either the EPM2A or NHLRC1 (EPM2B) gene. Methods We report genetic mutations and clinical courses of Lafora disease in 5 adolescents with homozygote NHLRC1 mutation and homozygous EPM2A mutation. Results A total 5 patients (3 female, 2 male) were presented with progressive myoclonic epilepsy. In all cases there were no problems at birth, childhood, and their psychomotor development were normal and attended regular school. In general seizures began around at 13–14 years old. Over the time they demostrated ataxia, and significant deterioration occurred in mental functions, myoclonus of the extremities started, and 3 of all patients were unable to walk unassisted and one of them died at 15 years old. Axillary skin biopsies were performed to all and Lafora bodies in cytoplasm were demostrated. All patients parents are second-degree relatives. Routine blood test, cerebrospinal fluid analaysis were normal. In three patients cranial magnetic resonance imaging (MRI) were normal, but 2 patients had mild serebral and serebellar atrophy. There were multifocal, from time-to-time generalized spike-wave activity were observed in their electroencephalography (EEG). Genetic analaysis for Lafora was studied and 2 patients (sublings) had same mutation) homozygous (c.336 C>A) p.Y112X mutation in EPM2A gene, homozygous (c.199 G>T) p. E67X mutation (2 patient had same mutation) in NHLRC1 gene, homozygous L 180V (CTG>GTC) mutation in EPM2A gene were detected. Conclusion LD is characterized by progressive myoclonic epilepsy and neurodegenerative symptoms. Therefore early recognation is diffucult. If patient show progressive myoclonic seizures with progressive mental deterotation, as well as ataxi we should consider LD