Case report of Lafora disease: a rare genetic disorder manifesting as progressive myoclonic epilepsy

Abstract

Background: Lafora disease (LD) is a rare, autosomal recessive progressive myoclonic epilepsy caused by mutations in EPM2A or EPM2B. It is characterized by abnormal glycogen metabolism leading to poly-glucosan deposits, known as Lafora bodies, in various tissues. LD typically manifests during adolescence with progressive neurological decline, including myoclonic seizures, cognitive impairment, and ataxia. Early diagnosis is critical for symptom management, yet the disease remains challenging to treat due to its refractory nature.

Case presentation: We report the case of a 15-year-old male who initially presented with tonic-clonic and myoclonic seizures, bilateral lower limb paralysis, and hand tremors. Despite normal initial imaging findings, subsequent clinical progression raised suspicion for progressive myoclonic epilepsy. Genetic testing identified a homozygous pathogenic variant in EPM2A, confirming the diagnosis of LD. electroencephalogram (EEG) findings evolved over time, showing generalized spikes, poly-spikes, and spike-wave complexes on a slow background, consistent with advanced LD. The patient's seizures proved refractory to standard anti-epileptic drugs, necessitating the addition of phenobarbital, metformin, and zonisamide, which eventually achieved partial seizure control. Family genetic screening identified heterozygous carriers without clinical symptoms, emphasizing the need for genetic counseling.

Conclusions: This case highlights the diagnostic challenges of LD, particularly in its early stages when clinical and imaging findings may be nonspecific. The report underscores the importance of genetic testing in confirming the diagnosis and tailoring management strategies. Despite limited treatment options, individualized multi-drug regimens may help achieve partial symptom control. Early recognition and comprehensive management, including family counseling, are essential in improving quality of life for patients and their families.

Keywords: EPM2A mutation; Lafora diseas; Neurological decline; Progressive myoclonic epilepsy; Refractory epilepsy.

Fig. 1

Brain MRI of our patient affected with Lafora disease

Fig. 2

Early recording’s picture exhibits general spikes/poly-spikes and spike-wave complexes layered over a slow 6 Hz theta background. While the picture emphasizes further advancement with more short-duration poly-spikes and more frequent spike-wave complexes, the middle image shows an elevated frequency of these discharges. In these pictures, “seizure waves” more especially, the distinctive epileptiform discharges noted fit the changing pattern found in Lafora illness