Unverricht-Lundborg disease (ULD) is a rare progressive myoclonic epilepsy disorder characterized by action- and stimulus-sensitive myoclonus, and tonic-clonic seizures with ataxia, but with only a mild cognitive decline over time¹.

Prevalence

Worldwide prevalence unknown; Finland prevalence 2-4/100,000. Found across ethnicities/ancestries, with population-dependent prevalence; highest in Tunisia, Algeria, Morocco, and Finland².

Age of Onset

Typical: 6-15²; Range: 6-18³.

HPO Terms

HP:0000726 Dementia HP:0000992 Cutaneous photosensitivity HP:0001249 Intellectual disability HP:0001251 Ataxia HP:0001256 Mild intellectual disability HP:0001260 Dysarthria HP:0001268 Mental deterioration HP:0001336 Myoclonus HP:0002069 Bilateral tonic-clonic seizure HP:0002070 Limb ataxia HP:0002080 Intention tremor HP:0002121 Generalized non-motor (absence) seizure HP:0002392 EEG with polyspike wave complexes HP:0007000 Morning myoclonic jerks HP:0010850 EEG with spike-wave complexes HP:0011182 Interictal epileptiform activity

Association

Mendelian

Locus

hg19chr21:45196323-45196360

hg38chr21:43776442-43776479

t2tchr21:42132054-42132091

Details

Affected individuals have an unstable 12-nucleotide (dodecamer) repeat expansion. Alleles containing 2-3 motifs are considered benign, while alleles with 30-125 repeats are fully penetrant³. Alleles in the range 12-17 repeats have been observed, however the individuals carrying them have not undergone clinical evaluation. Alleles in the range 4-11 and 18-29 repeats have not been reported to date.

Mechanism

LoF

The repeat expansion causes significantly reduced expression of cystatin-B protein².

Detection

Short-read sequencing cannot detect pathogenic expansions. Conventional PCR has detected normal range alleles, while Southern blotting approximates expanded allele size².

Year

1997⁴

Location in Gene

5' UTR

Gene Strand

Alleles

Ref. Motif

CGCGGGGCGGGG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CGCGGGGCGGGG

Pathogen. (gene)

CCCCGCCCCGCG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interrup. (gene)

–

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0009698

Checking your browser - reCAPTCHA

genereviews:NBK1142

Clinical picture of EPM1-Unverricht-Lundborg disease.

Reetta,Kälviäinen, Jelena,Khyuppenen, Päivi,Koskenkorva, Kai,Eriksson, Ritva,Vanninen, Esa,Mervaala

Epilepsia · 2008-03-05

pmid:18325013

Dodecamer repeat expansion in cystatin B gene in progressive myoclonus epilepsy.

M D,Lalioti, H S,Scott, C,Buresi, C,Rossier, A,Bottani, M A,Morris, A,Malafosse, S E,Antonarakis

Nature · 1997-04-24

pmid:9126745

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Genome-wide detection and clinical prioritization of tandem repeat outliers using long-read sequencing.

Sophia B,Gibson, Nikhita,Damaraju, J Gus,Gustafson, Elsa V,Balton, Sirisak,Chanprasert, Ian A,Glass, Martha,Horike-Pyne, Runjun D,Kumar, Kathleen A,Leppig, Chris,Lundberg, Jane,Ranchalis, Elisabeth A,Rosenthal, Andrew K,Solomon, Andrew B,Stergachis, Mark,Wener, Gail P,Jarvik, Elizabeth E,Blue, Katrina M,Dipple, Harriet,Dashnow, Lea M,Starita, Danny E,Miller

medRxiv : the preprint server for health sciences · 2026-05-01

pmid:42094143

Novel, complex configurations of the

Mark F,Bennett, Mark A,Corbett, Thessa,Kroes, Laura,Canafoglia, Karen L,Oliver, Jillian M,Cameron, Neblina,Sikta, Jacob,Munro, Liam G,Fearnley, Kristina,Ibañez, Arianna,Tucci, Sanjay M,Sisodiya, Michael S,Hildebrand, Ingrid E,Scheffer, Carolina,Courage, Anna-Elina,Lehesjoki, Loretta,Giuliano, Giuseppe,Didato, Silvana,Franceschetti, Jozef,Gecz, Samuel F,Berkovic, Melanie,Bahlo

Brain communications · 2025-11-03

pmid:41268177

Association of Non-Coding Repeat Expansions with Parkinson's Disease Risk: Evidence from a UK Biobank-Based Whole-Genome Sequencing Study.

Zhen,Hu, Qin-Qin,Yan, Jing-Jin,Wan, Yu,Fan, Jun,Liu

Movement disorders : official journal of the Movement Disorder Society · 2025-10-11

pmid:41074692

A novel c.116 - 117 del variant in Unverricht-Lundborg disease: first ULD report in large Chinese population and review of the pathogenetic variants in CSTB gene.

Pu,Miao, Yao,Ding, Zhidong,Cen, Yulan,Chen, Wei,Luo, Baorong,Zhang, Zhiying,Wu, Meiping,Ding, Shuang,Wang

Acta epileptologica · 2025-05-29

pmid:40442775

Approach to Progressive Myoclonic Epilepsies: Clinical Clues for Genetic Testing.

Prasanthi,Aripirala, Sujit Abajirao,Jagtap

Journal of child neurology · 2025-05-08

pmid:40340521

Discovery of a Novel Shared Variant Among

Sima,Chaudhari, Lavanya Prakash,Acharya, Dushyanth Babu,Jasti, Akshay Pramod,Ware, Sankar Prasad,Gorthi, Kapaettu,Satyamoorthy

International journal of genomics · 2024-08-10

pmid:39156922

CSTB gene replacement improves neuroinflammation, neurodegeneration and ataxia in murine type 1 progressive myoclonus epilepsy.

Emrah,Gumusgoz, Sahba,Kasiri, Mayank,Verma, Jun,Wu, Daniel,Villarreal Acha, Ummay,Marriam, Sharyl,Fyffe-Maricich, Amy,Lin, Xin,Chen, Steven J,Gray, Berge A,Minassian

Gene therapy · 2023-12-22

pmid:38135787

Short- and long-interval intracortical inhibition in EPM1 is related to genotype.

Katri,Silvennoinen, Laura,Säisänen, Jelena,Hyppönen, Saara M,Rissanen, Pasi A,Karjalainen, Sasha,D'Ambrosio, Diego,Jimenez-Jimenez, Sara,Zagaglia, John C,Rothwell, Simona,Balestrini, Sanjay M,Sisodiya, Petro,Julkunen, Esa,Mervaala, Reetta,Kälviäinen

Epilepsia · 2022-12-01

pmid:36398398

Insights into the Genetic Profile of Two Siblings Affected by Unverricht-Lundborg Disease Using Patient-Derived hiPSCs.

Valeria,Lucchino, Luana,Scaramuzzino, Stefania,Scalise, Michela,Lo Conte, Clara,Zannino, Giorgia Lucia,Benedetto, Umberto,Aguglia, Edoardo,Ferlazzo, Giovanni,Cuda, Elvira Immacolata,Parrotta

Cells · 2022-11-04

pmid:36359887

Locus EPM1 CSTB

Disease

Locus

Alleles

gnomAD

References

Additional Literature