U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Unverricht-Lundborg syndrome(EPM1; PME; EPM1A)

MedGen UID:
155923
Concept ID:
C0751785
Disease or Syndrome
Synonyms: Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg); Epilepsy, progressive myoclonic type 1; EPILEPSY, PROGRESSIVE MYOCLONIC, 1A; Epilepsy, progressive myoclonus 1; Myoclonic epilepsy of Unverricht and Lundborg; Myoclonus progressive epilepsy of Unverricht and Lundborg; Progressive myoclonus epilepsy baltic myoclonic epilepsy; Unverricht-Lundborg Disease
SNOMED CT: Unverricht-Lundborg syndrome (230423006); Unverricht-Lundborg disease (230423006); Baltic myoclonus epilepsy (230423006)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): CSTB (21q22.3)
 
Monarch Initiative: MONDO:0009698
OMIM®: 254800
Orphanet: ORPHA308

Disease characteristics

Excerpted from the GeneReview: Progressive Myoclonic Epilepsy Type 1
Progressive myoclonic epilepsy type 1(EPM1) is a neurodegenerative disorder characterized by onset from age six to 15 years, stimulus-sensitive myoclonus, and tonic-clonic epileptic seizures. Some years after the onset, ataxia, incoordination, intentional tremor, and dysarthria develop. Individuals with EPM1 are cognitively mostly within the normal range, but show emotional lability and depression. The epileptic seizures are usually well controlled by anti-seizure medication, but the myoclonic jerks are progressive, action activated, and treatment resistant, and can be severely disabling. [from GeneReviews]
Authors:
Anna-Elina Lehesjoki  |  Reetta Kälviäinen   view full author information

Additional descriptions

From OMIM
Myoclonic epilepsy of Unverricht and Lundborg, also known as progressive myoclonic epilepsy-1A (EPM1A), is an autosomal recessive disorder characterized by onset of neurodegeneration between 6 and 13 years of age. Although it is considered a progressive myoclonic epilepsy, it differs from other forms in that it appears to be progressive only in adolescence, with dramatic worsening of myoclonus and ataxia in the first 6 years after onset. The disease stabilizes in early adulthood, and myoclonus and ataxia may even improve, and there is minimal to no cognitive decline (summary by Ramachandran et al., 2009). Genetic Heterogeneity of Progressive Myoclonic Epilepsy Progressive myoclonic epilepsy refers to a clinically and genetically heterogeneous group of neurodegenerative disorders, usually with debilitating symptoms, although severity varies. See also EPM1B (612437), caused by mutation in the PRICKLE1 gene (608500); Lafora disease-1 (EPM2A; 254780), caused by mutation in the EPM2A gene (607566); Lafora disease-2 (EPM2B; 620681), caused by mutation in the NHLRC1 (608072) gene; EPM3 (611726), caused by mutation in the KCTD7 gene (611725); EPM4 (254900), caused by mutation in the SCARB2 gene (602257); EPM6 (614018), caused by mutation in the GOSR2 gene (604027); EPM7 (616187), caused by mutation in the KCNC1 gene (176258); EPM8 (616230), caused by mutation in the CERS1 gene (606919); EPM9 (616540), caused by mutation in the LMNB2 gene (150341); EPM10 (616640), caused by mutation in the PRDM8 gene (616639); EPM11 (618876), caused by mutation in the SEMA6B gene (608873); and EPM12 (619191), caused by mutation in the SLC7A6OS gene (619192). A form of progressive myoclonic epilepsy, formerly designated EPM5, is included in 607459 with the primary designation of spinocerebellar ataxia with epilepsy (SCAE). Other disorders characterized by progressive myoclonic epilepsy include the neuronal ceroid lipofuscinoses (see, e.g., CLN1 (256730); sialidosis (256550); MERFF (545000); and DRPLA (125370), among others (reviews by Ramachandran et al., 2009 and de Siqueira, 2010).)  http://www.omim.org/entry/254800
From MedlinePlus Genetics
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.  https://medlineplus.gov/genetics/condition/progressive-myoclonic-epilepsy-type-1

Clinical features

From HPO
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Mental deterioration
MedGen UID:
66713
Concept ID:
C0234985
Mental or Behavioral Dysfunction
Loss of previously present mental abilities, generally in adults.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
EEG with polyspike wave complexes
MedGen UID:
867392
Concept ID:
C4021757
Finding
The presence of complexes of repetitive spikes and waves in EEG.
Interictal epileptiform activity
MedGen UID:
869073
Concept ID:
C4023491
Finding
Epileptiform activity refers to distinctive EEG waves or complexes distinguished from background activity found in in a proportion of human subjects with epilepsy, but which can also be found in subjects without seizures. Interictal epileptiform activity refers to such activity that occurs in the absence of a clinical or subclinical seizure.
EEG with spike-wave complexes
MedGen UID:
869259
Concept ID:
C4023683
Finding
Complexes of spikes (<70 ms) and sharp waves (70-200 ms), which are sharp transient waves that have a strong association with epilepsy, in cerebral electrical activity recorded along the scalp by electroencephalography (EEG).
Generalized non-motor (absence) seizure
MedGen UID:
1385688
Concept ID:
C4316903
Disease or Syndrome
A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features.

Professional guidelines

PubMed

Bosak M, Sułek A, Łukasik M, Żak A, Słowik A, Lasek-Bal A
Epilepsy Behav 2020 Nov;112:107439. Epub 2020 Sep 10 doi: 10.1016/j.yebeh.2020.107439. PMID: 32920378
Lasek-Bal A, Lukasik M, Żak A, Sulek A, Bosak M
Seizure 2019 Jul;69:87-91. Epub 2019 Apr 10 doi: 10.1016/j.seizure.2019.04.008. PMID: 30999254
Guazzi GC, Federico A
Acta Neurol (Napoli) 1992 Aug-Dec;14(4-6):469-84. PMID: 1293989

Recent clinical studies

Etiology

Sipilä JOT, Kälviäinen R
Acta Neurol Scand 2022 Nov;146(5):690-693. Epub 2022 Sep 13 doi: 10.1111/ane.13706. PMID: 36097839Free PMC Article
Hosny H, El Tamawy M, Gouider R, Lesca G, Abdel Naseer M, Kishk N, Abdel-Hamid MS, Ashmawi A
Epilepsy Res 2021 Oct;176:106746. Epub 2021 Aug 25 doi: 10.1016/j.eplepsyres.2021.106746. PMID: 34474241
Hainque E, Blancher A, Mesnage V, Rivaud-Pechoux S, Bertrand A, Dupont S, Navarro V, Roze E, Gourfinkel-An I, Apartis E
Rev Neurol (Paris) 2018 Jan-Feb;174(1-2):56-65. Epub 2017 Jul 5 doi: 10.1016/j.neurol.2017.06.005. PMID: 28688606
Merwick A, O'Brien M, Delanty N
Epilepsia 2012 Sep;53 Suppl 4:81-91. doi: 10.1111/j.1528-1167.2012.03617.x. PMID: 22946725
Tassinari CA, Rubboli G, Parmeggiani L, Valzania F, Plasmati R, Riguzzi P, Michelucci R, Volpi L, Passarelli D, Meletti S
Adv Neurol 1995;67:181-97. PMID: 8848969

Diagnosis

Cameron JM, Ellis CA, Berkovic SF; ILAE Genetics Commission; ILAE Genetic Literacy Task Force
Epileptic Disord 2023 Oct;25(5):670-680. Epub 2023 Sep 6 doi: 10.1002/epd2.20152. PMID: 37616028Free PMC Article
Sipilä JOT, Kälviäinen R
Acta Neurol Scand 2022 Nov;146(5):690-693. Epub 2022 Sep 13 doi: 10.1111/ane.13706. PMID: 36097839Free PMC Article
Nasri A, Zidi S, Kacem I, Mrabet S, Ben Djebara M, Gargouri A, Leguern E, Gouider R
Epileptic Disord 2022 Feb 1;24(1):163-170. doi: 10.1684/epd.2021.1372. PMID: 34787084
Kälviäinen R, Khyuppenen J, Koskenkorva P, Eriksson K, Vanninen R, Mervaala E
Epilepsia 2008 Apr;49(4):549-56. Epub 2008 Mar 5 doi: 10.1111/j.1528-1167.2008.01546.x. PMID: 18325013
Tassinari CA, Rubboli G, Parmeggiani L, Valzania F, Plasmati R, Riguzzi P, Michelucci R, Volpi L, Passarelli D, Meletti S
Adv Neurol 1995;67:181-97. PMID: 8848969

Therapy

Ben-Menachem E, Baulac M, Hong SB, Cleveland JM, Reichel C, Schulz AL, Wagener G, Brandt C
Epilepsy Res 2021 Feb;170:106526. Epub 2020 Dec 4 doi: 10.1016/j.eplepsyres.2020.106526. PMID: 33461041
Canafoglia L, Ferlazzo E, Michelucci R, Striano P, Magaudda A, Gambardella A, Pasini E, Belcastro V, Riguzzi P, Fanella M, Granata T, Beccaria F, Trentini C, Bianchi A, Aguglia U, Panzica F, Franceschetti S
Neurology 2017 Oct 17;89(16):1691-1697. Epub 2017 Sep 20 doi: 10.1212/WNL.0000000000004518. PMID: 28931642
Genton P
Epilepsia 2010 Feb;51 Suppl 1:37-9. doi: 10.1111/j.1528-1167.2009.02441.x. PMID: 20331711
Kälviäinen R, Khyuppenen J, Koskenkorva P, Eriksson K, Vanninen R, Mervaala E
Epilepsia 2008 Apr;49(4):549-56. Epub 2008 Mar 5 doi: 10.1111/j.1528-1167.2008.01546.x. PMID: 18325013
Lehesjoki AE
Adv Neurol 2002;89:193-7. PMID: 11968445

Prognosis

Vogt H, Baisch T, Mueller-Pfeiffer C, Mothersill IW
Epileptic Disord 2023 Jun;25(3):297-308. Epub 2023 May 22 doi: 10.1002/epd2.20017. PMID: 37536959
Acharya JN, Acharya VJ
J Clin Neurophysiol 2023 Feb 1;40(2):100-108. Epub 2022 Jun 30 doi: 10.1097/WNP.0000000000000913. PMID: 36735458
Ben-Menachem E, Baulac M, Hong SB, Cleveland JM, Reichel C, Schulz AL, Wagener G, Brandt C
Epilepsy Res 2021 Feb;170:106526. Epub 2020 Dec 4 doi: 10.1016/j.eplepsyres.2020.106526. PMID: 33461041
Canafoglia L, Ferlazzo E, Michelucci R, Striano P, Magaudda A, Gambardella A, Pasini E, Belcastro V, Riguzzi P, Fanella M, Granata T, Beccaria F, Trentini C, Bianchi A, Aguglia U, Panzica F, Franceschetti S
Neurology 2017 Oct 17;89(16):1691-1697. Epub 2017 Sep 20 doi: 10.1212/WNL.0000000000004518. PMID: 28931642
Kälviäinen R, Khyuppenen J, Koskenkorva P, Eriksson K, Vanninen R, Mervaala E
Epilepsia 2008 Apr;49(4):549-56. Epub 2008 Mar 5 doi: 10.1111/j.1528-1167.2008.01546.x. PMID: 18325013

Clinical prediction guides

Sinokki A, Säisänen L, Hyppönen J, Silvennoinen K, Kälviäinen R, Mervaala E, Karjalainen PA, Rissanen SM
Clin Neurophysiol 2023 Dec;156:166-174. Epub 2023 Oct 26 doi: 10.1016/j.clinph.2023.10.005. PMID: 37952446
Acharya JN, Acharya VJ
J Clin Neurophysiol 2023 Feb 1;40(2):100-108. Epub 2022 Jun 30 doi: 10.1097/WNP.0000000000000913. PMID: 36735458
Sipilä JOT, Kälviäinen R
Acta Neurol Scand 2022 Nov;146(5):690-693. Epub 2022 Sep 13 doi: 10.1111/ane.13706. PMID: 36097839Free PMC Article
Danner N, Julkunen P, Hyppönen J, Niskanen E, Säisänen L, Könönen M, Koskenkorva P, Vanninen R, Kälviäinen R, Mervaala E
Mov Disord 2013 Nov;28(13):1860-7. Epub 2013 Aug 7 doi: 10.1002/mds.25615. PMID: 23925991
Koskenkorva P, Niskanen E, Hyppönen J, Könönen M, Mervaala E, Soininen H, Kälviäinen R, Vanninen R
AJNR Am J Neuroradiol 2012 May;33(5):878-83. Epub 2012 Jan 19 doi: 10.3174/ajnr.A2882. PMID: 22268086Free PMC Article

Recent systematic reviews

Yoganathan S, Whitney R, Thomas M, Danda S, Chettali AM, Prasad AN, Farhan SMK, AlSowat D, Abukhaled M, Aldhalaan H, Gowda VK, Kinhal UV, Bylappa AY, Konanki R, Lingappa L, Parchuri BM, Appendino JP, Scantlebury MH, Cunningham J, Hadjinicolaou A, El Achkar CM, Kamate M, Menon RN, Jose M, Riordan G, Kannan L, Jain V, Manokaran RK, Chau V, Donner EJ, Costain G, Minassian BA, Jain P
Epilepsia 2024 Mar;65(3):709-724. Epub 2024 Jan 17 doi: 10.1111/epi.17880. PMID: 38231304

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...