By: Imogen Ronde
What is Unverricht-Lundborg Disease?
Unverricht-Lundborg Disease is a type of progressive myoclonus epilepsy. While rare, it is the most common single cause of progressive myoclonus epilepsy (Joensuu et al, 2007). It has a late childhood and early adolescent onset, with a peak around ages 12-13 (Crespel et al, 2016).
History:
Unverricht-Lundborg Disease was first described in 1891 in Estonia by H. Unverricht, and in 1903 in Sweden by H. Lundborg (Crespel et al, 2016). Although there are cases worldwide, it was originally separated into Baltic myoclonus in patients from Finland, and Mediterranean myoclonus in Southern European and North African patients. These were unified into Unverricht-Lundborg in 1989, due to similar clinical presentation, which was later confirmed to be mutations in the same gene, on chromosome 21q22.3 (Magaudda et al, 2006).
What causes Unverricht-Lundborg Disease?
Unverricht-Lundborg Disease is caused by any of ten recessively inherited mutations on the cystatin-B gene on chromosome 21q22.3. The most common mutation is the expansion mutation, in which more triplets are present than in a healthy gene. This mutation is present in approximately 90% of the disease alleles. The other nine mutations all result in amino acid changes, altering how the cystatin-B gene interacts with other molecules and causing loss of function (Joensuu, 2007).
Signs and Symptoms:
People with Unverricht-Lundborg Disease have morning myoclonic jerks and limb ataxia, and show polyspike wave complexes on EEG. Some patients may also have difficulty articulating speech and intention tremor (U.S. Department of Health and Human Services). Many can also experience depression and a mild decline in intellectual functioning.
How is it diagnosed?
Unverricht-Lundborg Disease is diagnosed by myoclonus with ataxia and no major cognitive impairment, and thus should be confirmed by polyspike waves on EEG and genetic testing for the recessively inherited mutations on chromosome 21q22.3 (Ferlazzo et al, 2006).
Management and treatment:
Medications used to treat Unverricht-Lundborg Disease are sodium valproate, clonazepam, levetiracetam, and topiramate (Epilepsy Action, 2019). Options such as the Ketogenic Diet can be used to reduce seizure activity. People who are suffering from Unverricht-Lundborg Disease should avoid taking phenytoin, carbamazepine, and vigabatrin due to a potential increase in making the symptoms of myoclonus and ataxia worse (Epilepsy Action, 2019).
Prognosis:
The prognosis depends entirely on the severity of the condition, as many people with Unverricht-Lundborg Disease can lead normal and productive lives, while some patients will be severely disabled and rely upon caregivers for help with daily needs. This disease does have a limited progression, meaning that about five to ten years after the onset it will stabilize and the patient should not deteriorate any further, as long as seizures are well managed with anti-myoclonic medications (Crespel et al, 2016).
Resources:
Budworth, H., & McMurray, C. T. (2013). A brief history of triplet repeat diseases. Methods in molecular biology (Clifton, N.J.), 1010, 3–17. https://doi.org/10.1007/978-1-62703-411-1_1
Crespel, A., Ferlazzo, E., Franceschetti, S., Genton, P., Gouider, R., Kälviäinen, R., Korja, M., Lehtinen, M. K., Mervaala, E., Simonato, M., & Vaarmann, A. (2016). Unverricht-Lundborg disease. Epileptic Disorders, 18(S2), 28–37. https://doi.org/10.1684/epd.2016.0841
Epilepsy Action (2019). Unverricht-Lundborg Disease. Epilepsy Action. Retrieved from: https://www.epilepsy.org.uk/info/syndromes/unverricht-lundborg-syndrome
Ferlazzo, E., Magaudda, A., Striano, P., Vi-Hong, N., Serra, S., & Genton, P. (2007). Long-term evolution of EEG in Unverricht-Lundborg disease. Epilepsy Research, 73(3), 219–227. https://doi.org/10.1016/j.eplepsyres.2006.10.006
Joensuu, T., Lehesjoki, A.-E., & Kopra, O. (2008). Molecular background of EPM1—Unverricht–Lundborg disease. Epilepsia, 49(4), 557–563. https://doi.org/10.1111/j.1528-1167.2007.01422.x
Magaudda, A., Ferlazzo, E., Nguyen, V.-H., & Genton, P. (2006). Unverricht-Lundborg disease, a condition with self-limited progression: Long-term follow-up of 20 patients. Epilepsia, 47(5), 860–866. https://doi.org/10.1111/j.1528-1167.2006.00553.x
Medline Plus (2008). Unverricht-Lundborg Disease. MedLine Plus, National Library of Medicine. Retrieved from: https://medlineplus.gov/genetics/condition/unverricht-lundborg-disease/#:~:text=Eventually%20people%20with%20Unverricht%2DLundborg,mild%20decline%20in%20intellectual%20functioning.
U.S. Department of Health and Human Services. (n.d.). Unverricht-Lundborg disease. Genetic and Rare Diseases Information Center. Retrieved April 14, 2022, from https://rarediseases.info.nih.gov/diseases/3876/unverricht-lundborg-disease
