UnverrichtLundborg

Unverricht-Lundborg disease (ULD) is a rare autosomal recessive neurodegenerative disorder within the progressive myoclonus epilepsy spectrum. It stems from mutations in the CSTB gene, which encodes cystatin B, a cysteine protease inhibitor. The most common pathogenic mechanism is a dodecamer repeat expansion in the CSTB promoter that reduces cystatin B expression; other CSTB variants can also cause disease.

Onset is usually in childhood, commonly between 6 and 16 years. The early hallmark is stimulus-sensitive myoclonus, often accompanied by spreading generalized seizures. As the disease progresses, patients may develop ataxia, tremor, dysarthria, and gradual cognitive decline. Seizures and myoclonus can become disabling, though progression is variable.

Diagnosis relies on clinical suspicion supported by genetic testing for CSTB mutations, including testing for the characteristic dodecamer repeat expansion. Neonatal screening is not available. Neurophysiology may show generalized epileptiform discharges; brain imaging can reveal cerebellar atrophy in later stages.

Treatment is mainly symptomatic. Valproate and levetiracetam are commonly used to control myoclonus and seizures; clonazepam and other agents may help. Lamotrigine can worsen myoclonus in some cases. Physical and occupational therapy support function, and regular monitoring guides adjustment of therapy. There is no cure, and disease course varies.

Eponym: the disorder is named after physicians Unverricht and Lundborg, who described the condition in the early 20th century as a hereditary progressive myoclonus epilepsy.