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Myoclonic epilepsy of Lafora 1(MELF1)

MedGen UID:
1844054
Concept ID:
C5848203
Disease or Syndrome
Synonyms: EPILEPSY, PROGRESSIVE MYOCLONIC, 2A; EPM2A-Related Lafora Disease; LAFORA DISEASE 1; MELF1
 
Gene (location): EPM2A (6q24.3)
 
Monarch Initiative: MONDO:0958199
OMIM®: 254780

Definition

Any Lafora disease in which the cause of the disease is a variation in the EPM2A gene. [from MONDO]

Clinical features

From HPO
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Apraxia
MedGen UID:
8166
Concept ID:
C0003635
Mental or Behavioral Dysfunction
A defect in the understanding of complex motor commands and in the execution of certain learned movements, i.e., deficits in the cognitive components of learned movements.
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.
Psychotic disorder
MedGen UID:
19568
Concept ID:
C0033975
Mental or Behavioral Dysfunction
A condition characterized by changes in personality and thought patterns, often accompanied by hallucinations and delusional beliefs, is known as psychosis.
Visual hallucination
MedGen UID:
66688
Concept ID:
C0233763
Sign or Symptom
Visual perception in the absence of a visual stimulus.
Focal sensory seizure with visual features
MedGen UID:
75815
Concept ID:
C0278188
Disease or Syndrome
A seizure characterized by elementary visual hallucinations such as flashing or flickering lights/colors, or other shapes, simple patterns, scotomata, or amaurosis as its first clinical manifestation.
Lafora bodies
MedGen UID:
569348
Concept ID:
C0333749
Cell Component
An intraneuronal inclusion body composed of acid mucopolysaccharides.
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.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Bilateral tonic-clonic seizure with focal onset
MedGen UID:
164077
Concept ID:
C0877017
Disease or Syndrome
A bilateral tonic-clonic seizure with focal onset is a focal-onset seizure which progresses into a bilateral tonic-clonic phase.
Progressive neurologic deterioration
MedGen UID:
381506
Concept ID:
C1854838
Finding
Generalized myoclonic seizure
MedGen UID:
892704
Concept ID:
C4021759
Disease or Syndrome
A generalized myoclonic seizure is a type of generalized motor seizure characterized by bilateral, sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.
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.
Cutaneous photosensitivity
MedGen UID:
87601
Concept ID:
C0349506
Pathologic Function
An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.
Visual loss
MedGen UID:
784038
Concept ID:
C3665386
Finding
Loss of visual acuity (implying that vision was better at a certain time point in life). Otherwise the term reduced visual acuity should be used (or a subclass of that).

Professional guidelines

PubMed

Riva A, Orsini A, Scala M, Taramasso V, Canafoglia L, d'Orsi G, Di Claudio MT, Avolio C, D'Aniello A, Elia M, Franceschetti S, Di Gennaro G, Bisulli F, Tinuper P, Tappatà M, Romeo A, Freri E, Marini C, Costa C, Sofia V, Ferlazzo E, Magaudda A, Veggiotti P, Gennaro E, Pistorio A, Minetti C, Bianchi A, Striano S, Michelucci R, Zara F, Minassian BA, Striano P; Italian League Against Epilepsy Genetic Commission
J Neurol Sci 2021 May 15;424:117409. Epub 2021 Mar 20 doi: 10.1016/j.jns.2021.117409. PMID: 33773408Free PMC Article
Bisulli F, Muccioli L, d'Orsi G, Canafoglia L, Freri E, Licchetta L, Mostacci B, Riguzzi P, Pondrelli F, Avolio C, Martino T, Michelucci R, Tinuper P
Orphanet J Rare Dis 2019 Jun 21;14(1):149. doi: 10.1186/s13023-019-1132-3. PMID: 31227012Free PMC Article
Monaghan TS, Delanty N
CNS Drugs 2010 Jul;24(7):549-61. doi: 10.2165/11319250-000000000-00000. PMID: 20527995

Recent clinical studies

Etiology

Panchal U, Salazar de Pablo G, Franco M, Moreno C, Parellada M, Arango C, Fusar-Poli P
Eur Child Adolesc Psychiatry 2023 Jul;32(7):1151-1177. Epub 2021 Aug 18 doi: 10.1007/s00787-021-01856-w. PMID: 34406494Free PMC Article
Farah BL, Yen PM, Koeberl DD
Mol Genet Metab 2020 Jan;129(1):3-12. Epub 2019 Nov 21 doi: 10.1016/j.ymgme.2019.11.005. PMID: 31787497Free PMC Article
Orsini A, Valetto A, Bertini V, Esposito M, Carli N, Minassian BA, Bonuccelli A, Peroni D, Michelucci R, Striano P
Seizure 2019 Oct;71:247-257. Epub 2019 Aug 23 doi: 10.1016/j.seizure.2019.08.012. PMID: 31476531Free PMC Article
Cenacchi G, Papa V, Costa R, Pegoraro V, Marozzo R, Fanin M, Angelini C
Virchows Arch 2019 Dec;475(6):671-686. Epub 2019 Jul 30 doi: 10.1007/s00428-019-02633-6. PMID: 31363843
Kälviäinen R
Semin Neurol 2015 Jun;35(3):293-9. Epub 2015 Jun 10 doi: 10.1055/s-0035-1552620. PMID: 26060909

Diagnosis

Orsini A, Valetto A, Bertini V, Esposito M, Carli N, Minassian BA, Bonuccelli A, Peroni D, Michelucci R, Striano P
Seizure 2019 Oct;71:247-257. Epub 2019 Aug 23 doi: 10.1016/j.seizure.2019.08.012. PMID: 31476531Free PMC Article
Cenacchi G, Papa V, Costa R, Pegoraro V, Marozzo R, Fanin M, Angelini C
Virchows Arch 2019 Dec;475(6):671-686. Epub 2019 Jul 30 doi: 10.1007/s00428-019-02633-6. PMID: 31363843
Kälviäinen R
Semin Neurol 2015 Jun;35(3):293-9. Epub 2015 Jun 10 doi: 10.1055/s-0035-1552620. PMID: 26060909
Goebel HH, Müller HD
Ultrastruct Pathol 2013 Feb;37(1):19-22. doi: 10.3109/01913123.2012.670060. PMID: 23383614
Monaghan TS, Delanty N
CNS Drugs 2010 Jul;24(7):549-61. doi: 10.2165/11319250-000000000-00000. PMID: 20527995

Therapy

Donohue KJ, Fitzsimmons B, Bruntz RC, Markussen KH, Young LEA, Clarke HA, Coburn PT, Griffith LE, Sanders W, Klier J, Burke SN, Maurer AP, Minassian BA, Sun RC, Kordasiewisz HB, Gentry MS
Neurotherapeutics 2023 Oct;20(6):1808-1819. Epub 2023 Sep 12 doi: 10.1007/s13311-023-01434-9. PMID: 37700152Free PMC Article
Zeka N, Zogaj L, Gerguri A, Bejiqi R, Ratkoceri R, Maloku A, Mustafa A, Shahini L, Maxharaj J
J Med Case Rep 2022 Oct 3;16(1):360. doi: 10.1186/s13256-022-03537-x. PMID: 36192771Free PMC Article
Deniz K
Turk Patoloji Derg 2021;37(1):51-55. doi: 10.5146/tjpath.2020.01510. PMID: 33021734Free PMC Article
Coşkun T, Kiziltan M, Gündüz A, Delil Ş, Yeni N, Özkara Ç
Seizure 2015 Jul;29:169-73. Epub 2015 May 15 doi: 10.1016/j.seizure.2015.05.006. PMID: 26076862
Monaghan TS, Delanty N
CNS Drugs 2010 Jul;24(7):549-61. doi: 10.2165/11319250-000000000-00000. PMID: 20527995

Prognosis

Pondrelli F, Minardi R, Muccioli L, Zenesini C, Vignatelli L, Licchetta L, Mostacci B, Tinuper P, Vander Kooi CW, Gentry MS, Bisulli F
Orphanet J Rare Dis 2023 Sep 2;18(1):263. doi: 10.1186/s13023-023-02880-6. PMID: 37658439Free PMC Article
Orsini A, Valetto A, Bertini V, Esposito M, Carli N, Minassian BA, Bonuccelli A, Peroni D, Michelucci R, Striano P
Seizure 2019 Oct;71:247-257. Epub 2019 Aug 23 doi: 10.1016/j.seizure.2019.08.012. PMID: 31476531Free PMC Article
Kecmanović M, Jović N, Keckarević-Marković M, Keckarević D, Stevanović G, Ignjatović P, Romac S
Clin Genet 2016 Jan;89(1):104-8. Epub 2015 Mar 19 doi: 10.1111/cge.12570. PMID: 25683376
Kälviäinen R
Semin Neurol 2015 Jun;35(3):293-9. Epub 2015 Jun 10 doi: 10.1055/s-0035-1552620. PMID: 26060909
Goebel HH, Müller HD
Ultrastruct Pathol 2013 Feb;37(1):19-22. doi: 10.3109/01913123.2012.670060. PMID: 23383614

Clinical prediction guides

Riva A, Orsini A, Scala M, Taramasso V, Canafoglia L, d'Orsi G, Di Claudio MT, Avolio C, D'Aniello A, Elia M, Franceschetti S, Di Gennaro G, Bisulli F, Tinuper P, Tappatà M, Romeo A, Freri E, Marini C, Costa C, Sofia V, Ferlazzo E, Magaudda A, Veggiotti P, Gennaro E, Pistorio A, Minetti C, Bianchi A, Striano S, Michelucci R, Zara F, Minassian BA, Striano P; Italian League Against Epilepsy Genetic Commission
J Neurol Sci 2021 May 15;424:117409. Epub 2021 Mar 20 doi: 10.1016/j.jns.2021.117409. PMID: 33773408Free PMC Article
Beniczky S, Aurlien H, Franceschetti S, Martins da Silva A, Bisulli F, Bentes C, Canafoglia L, Ferri L, Krýsl D, Rita Peralta A, Rácz A, Cross JH, Arzimanoglou A
Epilepsia 2020 Sep;61(9):e124-e128. Epub 2020 Sep 19 doi: 10.1111/epi.16655. PMID: 32949474
Kecmanović M, Jović N, Keckarević-Marković M, Keckarević D, Stevanović G, Ignjatović P, Romac S
Clin Genet 2016 Jan;89(1):104-8. Epub 2015 Mar 19 doi: 10.1111/cge.12570. PMID: 25683376
Goebel HH, Müller HD
Ultrastruct Pathol 2013 Feb;37(1):19-22. doi: 10.3109/01913123.2012.670060. PMID: 23383614
Sedel F, Gourfinkel-An I, Lyon-Caen O, Baulac M, Saudubray JM, Navarro V
J Inherit Metab Dis 2007 Nov;30(6):846-54. Epub 2007 Oct 22 doi: 10.1007/s10545-007-0723-7. PMID: 17957491

Recent systematic reviews

Pondrelli F, Minardi R, Muccioli L, Zenesini C, Vignatelli L, Licchetta L, Mostacci B, Tinuper P, Vander Kooi CW, Gentry MS, Bisulli F
Orphanet J Rare Dis 2023 Sep 2;18(1):263. doi: 10.1186/s13023-023-02880-6. PMID: 37658439Free PMC Article
Panchal U, Salazar de Pablo G, Franco M, Moreno C, Parellada M, Arango C, Fusar-Poli P
Eur Child Adolesc Psychiatry 2023 Jul;32(7):1151-1177. Epub 2021 Aug 18 doi: 10.1007/s00787-021-01856-w. PMID: 34406494Free PMC Article
Pondrelli F, Muccioli L, Licchetta L, Mostacci B, Zenesini C, Tinuper P, Vignatelli L, Bisulli F
Orphanet J Rare Dis 2021 Aug 16;16(1):362. doi: 10.1186/s13023-021-01989-w. PMID: 34399803Free PMC Article
Muccioli L, Farolfi A, Pondrelli F, d'Orsi G, Michelucci R, Freri E, Canafoglia L, Licchetta L, Toni F, Bonfiglioli R, Civollani S, Pettinato C, Maietti E, Marotta G, Fanti S, Tinuper P, Bisulli F
Eur J Nucl Med Mol Imaging 2020 Jun;47(6):1576-1584. Epub 2019 Dec 19 doi: 10.1007/s00259-019-04647-3. PMID: 31858178

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