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Progressive myoclonic epilepsy type 9(EPM9)

MedGen UID:
901242
Concept ID:
C4225289
Disease or Syndrome
Synonyms: EPILEPSY, PROGRESSIVE MYOCLONIC, 9; EPM9
SNOMED CT: Progressive myoclonic epilepsy type 9 (1228857005); Progressive myoclonic epilepsy due to LMNB2 deficiency (1228857005); Progressive myoclonic epilepsy due to LMNB2 (lamin B2) deficiency (1228857005); Progressive myoclonus epilepsy type 9 (1228857005); PME (progressive myoclonic epilepsy) type 9 (1228857005)
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): LMNB2 (19p13.3)
 
Monarch Initiative: MONDO:0014685
OMIM®: 616540
Orphanet: ORPHA457265

Definition

A rare genetic neurological disorder with characteristics of childhood-onset severe myoclonic and tonic-clonic seizures and early-onset ataxia leading to severe gait disturbances associated with normal to slightly diminished cognition. Scoliosis, diffuse muscle atrophy and subcutaneous fat loss, as well as developmental delay, may be associated. Brain MRI may reveal complete agenesis of the corpus callosum, ventriculomegaly, interhemispheric cysts and simplified gyration (frontally). [from SNOMEDCT_US]

Clinical features

From HPO
Short thumb
MedGen UID:
98469
Concept ID:
C0431890
Congenital Abnormality
Hypoplasia (congenital reduction in size) of the thumb.
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.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
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.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Action myoclonus
MedGen UID:
155545
Concept ID:
C0751354
Sign or Symptom
A type of myoclonus (arrhythmic muscular jerking) that is induced by voluntary movement. It is made worse by attempts at precise or coordinated movement (intention myoclonus) and may also be provoked by certain sensory stimuli.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Interhemispheric cyst
MedGen UID:
339924
Concept ID:
C1853188
Disease or Syndrome
Cystic collection (sac-like, fluid containing pocket of membranous tissue) located in the interhemispheric fissure, with or without communication with the ventricular system.
Simplified gyral pattern
MedGen UID:
413664
Concept ID:
C2749675
Finding
An abnormality of the cerebral cortex with fewer gyri but with normal cortical thickness. This pattern is usually often associated with congenital microcephaly.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Generalized myoclonic seizure
MedGen UID:
892704
Concept ID:
C4021759
Disease or Syndrome
A generalized myoclonic seizure is a type of generalized motor seizure characterised 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.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Frequent falls
MedGen UID:
163408
Concept ID:
C0850703
Finding
Generalized amyotrophy
MedGen UID:
234650
Concept ID:
C1389113
Disease or Syndrome
Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.
Microglossia
MedGen UID:
10029
Concept ID:
C0025988
Congenital Abnormality
Decreased length and width of the tongue.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVProgressive myoclonic epilepsy type 9

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

Recent clinical studies

Etiology

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
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
Beltrán L, Valenzuela GR, Loos M, Vargas R, Lizama R, Spinsanti P, Caraballo R
Epilepsy Res 2018 Aug;144:49-52. Epub 2018 May 16 doi: 10.1016/j.eplepsyres.2018.05.005. PMID: 29778029
Moen MN, Fjær R, Hamdani EH, Laerdahl JK, Menchini RJ, Vigeland MD, Sheng Y, Undlien DE, Hassel B, Salih MA, El Khashab HY, Selmer KK, Chaudhry FA
Brain 2016 Dec;139(Pt 12):3109-3120. Epub 2016 Oct 14 doi: 10.1093/brain/aww244. PMID: 27742667
Buchhalter JR
J Child Neurol 1994 Oct;9 Suppl 1:S12-9. doi: 10.1177/0883073894009001041. PMID: 7822747

Diagnosis

Hyppönen J, Paanila V, Äikiä M, Koskenkorva P, Könönen M, Vanninen R, Mervaala E, Kälviäinen R, Hakumäki J
Neuroimage Clin 2023;39:103459. Epub 2023 Jul 3 doi: 10.1016/j.nicl.2023.103459. PMID: 37541097Free 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
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
Berkovic SF, Oliver KL, Canafoglia L, Krieger P, Damiano JA, Hildebrand MS, Morbin M, Vears DF, Sofia V, Giuliano L, Garavaglia B, Simonati A, Santorelli FM, Gambardella A, Labate A, Belcastro V, Castellotti B, Ozkara C, Zeman A, Rankin J, Mole SE, Aguglia U, Farrell M, Rajagopalan S, McDougall A, Brammah S, Andermann F, Andermann E, Dahl HM, Franceschetti S, Carpenter S
Brain 2019 Jan 1;142(1):59-69. doi: 10.1093/brain/awy297. PMID: 30561534
Beltrán L, Valenzuela GR, Loos M, Vargas R, Lizama R, Spinsanti P, Caraballo R
Epilepsy Res 2018 Aug;144:49-52. Epub 2018 May 16 doi: 10.1016/j.eplepsyres.2018.05.005. PMID: 29778029

Therapy

Browner N, Azher SN, Jankovic J
Mov Disord 2006 Sep;21(9):1500-2. doi: 10.1002/mds.20991. PMID: 16758485
Prescrire Int 2005 Apr;14(76):57-9. PMID: 15875342
Doose H, Lunau H, Castiglione E, Waltz S
Neuropediatrics 1998 Oct;29(5):229-38. doi: 10.1055/s-2007-973567. PMID: 9810557
Genton P, Guerrini R
Neurology 1990 Sep;40(9):1412-6. doi: 10.1212/wnl.40.9.1412. PMID: 2118240

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
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
Pan S, Li X, Li L, Lin H, Wang D, Zhang X, Zhao X, Ye J, Huang Z, Lin Y, Duan Y, Ma R, Gao L, Wang C, Wang Y
Seizure 2021 Apr;87:69-74. Epub 2021 Feb 23 doi: 10.1016/j.seizure.2021.02.026. PMID: 33721773
Berkovic SF, Oliver KL, Canafoglia L, Krieger P, Damiano JA, Hildebrand MS, Morbin M, Vears DF, Sofia V, Giuliano L, Garavaglia B, Simonati A, Santorelli FM, Gambardella A, Labate A, Belcastro V, Castellotti B, Ozkara C, Zeman A, Rankin J, Mole SE, Aguglia U, Farrell M, Rajagopalan S, McDougall A, Brammah S, Andermann F, Andermann E, Dahl HM, Franceschetti S, Carpenter S
Brain 2019 Jan 1;142(1):59-69. doi: 10.1093/brain/awy297. PMID: 30561534
Buchhalter JR
J Child Neurol 1994 Oct;9 Suppl 1:S12-9. doi: 10.1177/0883073894009001041. PMID: 7822747

Clinical prediction guides

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
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
Berkovic SF, Oliver KL, Canafoglia L, Krieger P, Damiano JA, Hildebrand MS, Morbin M, Vears DF, Sofia V, Giuliano L, Garavaglia B, Simonati A, Santorelli FM, Gambardella A, Labate A, Belcastro V, Castellotti B, Ozkara C, Zeman A, Rankin J, Mole SE, Aguglia U, Farrell M, Rajagopalan S, McDougall A, Brammah S, Andermann F, Andermann E, Dahl HM, Franceschetti S, Carpenter S
Brain 2019 Jan 1;142(1):59-69. doi: 10.1093/brain/awy297. PMID: 30561534
Chambers JK, Thongtharb A, Shiga T, Azakami D, Saito M, Sato M, Morozumi M, Nakayama H, Uchida K
Vet Pathol 2018 Jul;55(4):543-551. Epub 2018 Feb 14 doi: 10.1177/0300985818758471. PMID: 29444631
Oliver KL, Franceschetti S, Milligan CJ, Muona M, Mandelstam SA, Canafoglia L, Boguszewska-Chachulska AM, Korczyn AD, Bisulli F, Di Bonaventura C, Ragona F, Michelucci R, Ben-Zeev B, Straussberg R, Panzica F, Massano J, Friedman D, Crespel A, Engelsen BA, Andermann F, Andermann E, Spodar K, Lasek-Bal A, Riguzzi P, Pasini E, Tinuper P, Licchetta L, Gardella E, Lindenau M, Wulf A, Møller RS, Benninger F, Afawi Z, Rubboli G, Reid CA, Maljevic S, Lerche H, Lehesjoki AE, Petrou S, Berkovic SF
Ann Neurol 2017 May;81(5):677-689. doi: 10.1002/ana.24929. PMID: 28380698

Recent systematic reviews

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

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