Lafora disease (LD) is an autosomal recessive progressive myoclonic epilepsy with cognitive decline with typical onset in late childhood to early adolescence[1]. Lafora disease is caused by loss-of-function mutations in EPM2A or NHLRC1 which encode laforin and malin, respectively[2]. Lafora bodies are typically found in the brain, periportal hepatocytes of the liver, skeletal and cardiac myocytes, and in the eccrine duct and apocrine myoepithelial cells of sweat glands[3]. We present a child with clinical phenotype of LD with a novel homozygous c.575A>T (p.Asp192Val) variant in NHLRC1, likely pathogenic.

Proband is a 15-year-old male with abnormal movements described as uncontrolled shaking of his hands and legs associated with screaming and extreme fear preceding the episode. These events were captured with vertex (Right>Left) and right frontal central regions seizure on EEG. He developed visual and auditory hallucination, cognitive decline, hearing impairment, 1^st degree heart block and hypertension. He later acquired oropharyngeal dysphagia and myoclonus causing difficulty ambulating and falls with leg fracture resulting in wheelchair dependence.

Epilepsy gene panel showed a homozygous c.575A>T (p.Asp192Val) variant previously classified as uncertain significance. His parents, who are first cousins, were carriers. Median nerve somatosensory evoked potential amplitudes were abnormally large bilaterally. This is indicative of hyperexcitability of sensorimotor cortex and consistent with a diagnosis of Lafora body disease.  Axillary skin biopsy demonstrated Lafora bodies.

Lafora disease is a rare autosomal recessive disorder We describe an adolescent with typical features and diagnostic skin pathology with a previously unreported variant. Therefore, we suggest reclassifying the c.575A>T (p.Asp192Val) variant in NHLRC1 as pathogenic.