Rationale:
Unverricht-Lundborg Disease (ULD) is a rare autosomal recessive form of progressive myoclonic epilepsy type 1 characterized by neurodegeneration and frequently delayed diagnosis.(1) We present an exceptionally rare case of two male siblings with genetically confirmed ULD, followed and managed over an extended period. This case report focuses on disease onset, clinical course, diagnostic workup including genetic testing, and management.
Methods:
Two biological male siblings, currently aged 40 and 38, were born healthy and had normal neurological development until age 7. Their disease began with stimulus-induced myoclonus and generalized tonic-clonic seizures (GTCs). Triggers included light, sound, heat, and touch, leading to frequent falls and injuries. Around puberty, both developed progressive ataxia and gait impairment, becoming wheelchair-bound in their early 30s. Additional symptoms included dysphagia requiring gastric tube placement. Cognitive decline progressed slowly; both maintained academic performance until high school. Currently, both require full-time dependent care in a group home. Notably, the older sibling exhibited early-onset psychiatric symptoms, including confabulation, hallucinations, and delusions, while the younger sibling retained insight but experienced chronic depression.
Results:
Initial diagnostic workup, including routine laboratory tests and brain MRI, was unremarkable. EEG revealed generalized spike/polyspike wave discharges and epileptic myoclonus (see Figure 1) and ( Figure 2). Genetic testing confirmed an EPM1 gene mutation coding for cystatin B; both parents were identified carriers. Seizures were refractory, requiring antiepileptic polytherapy. The current regimen includes clonazepam, valproic acid, felbamate, brivaracetam, and cannabidiol. The younger sibling also requires zonisamide. While stimulus-sensitive myoclonic jerks persist, GTCs are more controlled.
Conclusions:
In cases of stimulus-induced myoclonus, progressive GTCs, and ataxia with cognitive decline, clinicians should consider Progressive Myoclonic Epilepsy type 1 (ULD) and confirm with genetic testing. Antiepileptic polytherapy is required. While stimulus-sensitive myoclonic jerks can be resistant, GTCs may respond favorably to treatment.2
References
1- Lasek-Bal A, Lukasik M, Żak A, Sulek A, Bosak M. Unverricht-Lundborg disease: Clinical course and seizure management based on the experience of polish centers. Seizure. 2019;69:87-91. doi:10.1016/j.seizure.2019.04.008
2-Satishchandra P, Sinha S. Progressive myoclonic epilepsy. Neurol India. 2010;58(4):514-522. doi:10.4103/0028-3886.68660
Funding: None