Progressive myoclonic epilepsy type 1 (also called Unverricht-Lundborg disease or ULD) is a rare inherited form of epilepsy. Early development is normal in affected individuals. Signs and symptoms of the disorder typically begin between 6 and 15 years of age.

People with progressive myoclonic epilepsy type 1 experience episodes of involuntary muscle jerking or twitching (myoclonus) that increase in frequency and severity over time. Episodes of myoclonus may be brought on by physical exertion, stress, light, or other stimuli. Within 5 to 10 years, the myoclonic episodes may become severe enough to interfere with walking and other everyday activities.

Affected individuals also usually have seizures that involve loss of consciousness, muscle rigidity, and convulsions (tonic-clonic or grand mal seizures). Like the myoclonic episodes, these may increase in frequency over several years. However, the seizures may be controlled with treatment. After several years of progression, the frequency of seizures may stabilize or decrease.

Eventually, people with progressive myoclonic epilepsy type 1 may develop problems with balance and coordination (ataxia) and speaking (dysarthria). They may also experience depression. Another feature of this condition is involuntary rhythmic shaking. This shaking is called intentional tremor because it worsens during intentional movements.

People with progressive myoclonic epilepsy type 1 may live into adulthood. Life expectancy depends on the severity of the condition and a person's response to treatment. The severity of the condition can vary, even among members of the same family.

Progressive myoclonus epilepsy is a rare group of conditions.  Progressive myoclonic epilepsy type 1 is believed to be the most common form of this type of epilepsy, but its worldwide prevalence is unknown. The condition is more common in the North African countries of Tunisia, Algeria, and Morocco.  Progressive myoclonic epilepsy type 1 occurs most frequently in Finland, where approximately 2 in 100,000 people are affected.

Variants (also called mutations) in the CSTB gene cause progressive myoclonic epilepsy type 1. The CSTB gene provides instructions for making a protein called cystatin B. This protein reduces the activity of enzymes called cathepsins. Cathepsins help break down certain proteins in the lysosomes, which are compartments in the cell that digest and recycle different types of molecules. While the specific function of cystatin B is unclear, it may help protect the cells' proteins from cathepsins that leak out of the lysosomes.

In almost all affected individuals, progressive myoclonic epilepsy type 1 is caused by variants that affect the amount of cystatin B that is produced. One region of DNA that controls the activity of the CSTB gene has a particular repeating sequence of 12 DNA building blocks (nucleotides). This sequence is known as the dodecamer repeat. Normally, this sequence is repeated two or three times. However, in most people with progressive myoclonic epilepsy type 1, this sequence is repeated more than 30 times (called a repeat expansion). Most people with progressive myoclonic epilepsy type 1 have two copies of this variant.

A small number of people with progressive myoclonic epilepsy type 1 have one copy of the dodecamer repeat expansion and one copy of the CSTB gene with another type of variant. These other variants can include the substitution of a single nucleotide that impairs the gene's function.

In individuals with progressive myoclonic epilepsy type 1, levels of cystatin B are only 5 to 10 percent of normal. This change is believed to cause the signs and symptoms of progressive myoclonic epilepsy type 1, but it is unclear how a reduction in the amount of cystatin B leads to the features of this disorder.

Genetic Testing Information

• Genetic Testing Registry: Unverricht-Lundborg syndrome

Genetic and Rare Diseases Information Center

• Progressive myoclonic epilepsy type 1

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• MYOCLONIC EPILEPSY OF UNVERRICHT AND LUNDBORG

Scientific Articles on PubMed

• PubMed

• Alakurtti K, Virtaneva K, Joensuu T, Palvimo JJ, Lehesjoki AE. Characterization of the cystatin B gene promoter harboring the dodecamer repeat expanded in progressive myoclonus epilepsy, EPM1. Gene. 2000 Jan 25;242(1-2):65-73. doi: 10.1016/s0378-1119(99)00550-8. Citation on PubMed
• Alakurtti K, Weber E, Rinne R, Theil G, de Haan GJ, Lindhout D, Salmikangas P, Saukko P, Lahtinen U, Lehesjoki AE. Loss of lysosomal association of cystatin B proteins representing progressive myoclonus epilepsy, EPM1, mutations. Eur J Hum Genet. 2005 Feb;13(2):208-15. doi: 10.1038/sj.ejhg.5201300. Citation on PubMed
• Ceru S, Rabzelj S, Kopitar-Jerala N, Turk V, Zerovnik E. Protein aggregation as a possible cause for pathology in a subset of familial Unverricht-Lundborg disease. Med Hypotheses. 2005;64(5):955-9. doi: 10.1016/j.mehy.2004.11.038. Citation on PubMed
• Houseweart MK, Pennacchio LA, Vilaythong A, Peters C, Noebels JL, Myers RM. Cathepsin B but not cathepsins L or S contributes to the pathogenesis of Unverricht-Lundborg progressive myoclonus epilepsy (EPM1). J Neurobiol. 2003 Sep 15;56(4):315-27. doi: 10.1002/neu.10253. Citation on PubMed
• Joensuu T, Kuronen M, Alakurtti K, Tegelberg S, Hakala P, Aalto A, Huopaniemi L, Aula N, Michellucci R, Eriksson K, Lehesjoki AE. Cystatin B: mutation detection, alternative splicing and expression in progressive myclonus epilepsy of Unverricht-Lundborg type (EPM1) patients. Eur J Hum Genet. 2007 Feb;15(2):185-93. doi: 10.1038/sj.ejhg.5201723. Epub 2006 Sep 27. Citation on PubMed
• Lalioti MD, Antonarakis SE, Scott HS. The epilepsy, the protease inhibitor and the dodecamer: progressive myoclonus epilepsy, cystatin b and a 12-mer repeat expansion. Cytogenet Genome Res. 2003;100(1-4):213-23. doi: 10.1159/000072857. Citation on PubMed
• Lehesjoki AE, Kalviainen R. Progressive Myoclonic Epilepsy Type 1. 2004 Jun 24 [updated 2020 Jul 2]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1142/ Citation on PubMed
• Lehesjoki AE. Molecular background of progressive myoclonus epilepsy. EMBO J. 2003 Jul 15;22(14):3473-8. doi: 10.1093/emboj/cdg338. Citation on PubMed or Free article on PubMed Central
• Magaudda A, Ferlazzo E, Nguyen VH, Genton P. Unverricht-Lundborg disease, a condition with self-limited progression: long-term follow-up of 20 patients. Epilepsia. 2006 May;47(5):860-6. doi: 10.1111/j.1528-1167.2006.00553.x. Citation on PubMed
• Moulard B, Darcel F, Mignard D, Jeanpierre M, Genton P, Cartault F, Yaouanq J, Roubertie A, Biraben A, Buresi C, Malafosse A. FOunder effect in patients with Unverricht-Lundborg disease on reunion island. Epilepsia. 2003 Oct;44(10):1357-60. doi: 10.1046/j.1528-1157.2003.03703.x. Citation on PubMed
• Moulard B, Genton P, Grid D, Jeanpierre M, Ouazzani R, Mrabet A, Morris M, LeGuern E, Dravet C, Mauguiere F, Utermann B, Baldy-Moulinier M, Belaidi H, Bertran F, Biraben A, Ali Cherif A, Chkili T, Crespel A, Darcel F, Dulac O, Geny C, Humbert-Claude V, Kassiotis P, Buresi C, Malafosse A. Haplotype study of West European and North African Unverricht-Lundborg chromosomes: evidence for a few founder mutations. Hum Genet. 2002 Sep;111(3):255-62. doi: 10.1007/s00439-002-0755-x. Epub 2002 Jul 23. Citation on PubMed
• Shahwan A, Farrell M, Delanty N. Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects. Lancet Neurol. 2005 Apr;4(4):239-48. doi: 10.1016/S1474-4422(05)70043-0. Citation on PubMed