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Progressive myoclonic epilepsy type 8(EPM8)

MedGen UID:
1680582
Concept ID:
C5190825
Disease or Syndrome
Synonyms: EPILEPSY, PROGRESSIVE MYOCLONIC, 8; EPM8
SNOMED CT: Progressive myoclonic epilepsy type 8 (783139000); Progressive myoclonus epilepsy type 8 (783139000); Progressive myoclonic epilepsy due to CERS1 (ceramide synthase 1) deficiency (783139000); Progressive myoclonic epilepsy due to ceramide synthase 1 deficiency (783139000); PME (progressive myoclonic epilepsy) type 8 (783139000)
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): CERS1 (19p13.11)
 
Monarch Initiative: MONDO:0014545
OMIM®: 616230
Orphanet: ORPHA424027

Definition

Progressive myoclonic epilepsy-8 (EPM8) is a rare autosomal recessive form of progressive myoclonic epilepsy with phenotypic variability including ataxia and other movement disorders in addition to myoclonus (summary by Godeiro et al., 2018). For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800). [from OMIM]

Clinical features

From HPO
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.
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.
Choreoathetosis
MedGen UID:
39313
Concept ID:
C0085583
Disease or Syndrome
Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).
Falls
MedGen UID:
39084
Concept ID:
C0085639
Finding
A sudden movement downward, usually resulting in injury.
Truncal ataxia
MedGen UID:
96535
Concept ID:
C0427190
Sign or Symptom
Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
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.
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.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Limb ataxia
MedGen UID:
196692
Concept ID:
C0750937
Finding
A kind of ataxia that affects movements of the extremities.
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.
Progressive neurologic deterioration
MedGen UID:
381506
Concept ID:
C1854838
Finding
EEG with photoparoxysmal response
MedGen UID:
765735
Concept ID:
C3552821
Finding
EEG abnormalities (epileptiform discharges) evoked by flashing lights or black and white striped patterns.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Atrophy/Degeneration affecting the brainstem
MedGen UID:
870454
Concept ID:
C4024900
Disease or Syndrome
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVProgressive myoclonic epilepsy type 8

Professional guidelines

PubMed

Mir A, Alghamdi A, Alotaibi W, Samreen D, Alotaibi M, Albaradie R, Bashir S
Epileptic Disord 2022 Aug 1;24(4):633-646. doi: 10.1684/epd.2022.1439. PMID: 35770766
Rus CM, Weissensteiner T, Pereira C, Susnea I, Danquah BD, Morales Torres G, Rocha ME, Cozma C, Saravanakumar D, Mannepalli S, Kandaswamy KK, Di Bucchianico S, Zimmermann R, Rolfs A, Bauer P, Beetz C
Orphanet J Rare Dis 2022 May 3;17(1):179. doi: 10.1186/s13023-022-02288-8. PMID: 35505348Free PMC Article

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
Castellotti B, Canafoglia L, Freri E, Tappatà M, Messina G, Magri S, DiFrancesco JC, Fanella M, Di Bonaventura C, Morano A, Granata T, Gellera C, Franceschetti S, Michelucci R
Epilepsia Open 2023 Jun;8(2):645-650. Epub 2023 Feb 9 doi: 10.1002/epi4.12697. PMID: 36719163Free PMC Article
Mir A, Alghamdi A, Alotaibi W, Samreen D, Alotaibi M, Albaradie R, Bashir S
Epileptic Disord 2022 Aug 1;24(4):633-646. doi: 10.1684/epd.2022.1439. PMID: 35770766
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
Oguri M, Saito Y, Okanishi T, Matuura Y, Akiyama S, Ikeguchi T, Narita A, Hirooka Y, Maegaki Y
Brain Dev 2020 Jan;42(1):19-27. Epub 2019 Sep 24 doi: 10.1016/j.braindev.2019.08.005. PMID: 31561936

Diagnosis

Mir A, Alghamdi A, Alotaibi W, Samreen D, Alotaibi M, Albaradie R, Bashir S
Epileptic Disord 2022 Aug 1;24(4):633-646. doi: 10.1684/epd.2022.1439. PMID: 35770766
Rus CM, Weissensteiner T, Pereira C, Susnea I, Danquah BD, Morales Torres G, Rocha ME, Cozma C, Saravanakumar D, Mannepalli S, Kandaswamy KK, Di Bucchianico S, Zimmermann R, Rolfs A, Bauer P, Beetz C
Orphanet J Rare Dis 2022 May 3;17(1):179. doi: 10.1186/s13023-022-02288-8. PMID: 35505348Free 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
Ferranti S, Lo Rizzo C, Renieri A, Galluzzi P, Grosso S
Neurol Sci 2020 Nov;41(11):3345-3348. Epub 2020 May 21 doi: 10.1007/s10072-020-04418-1. PMID: 32440981
Opri R, Fabrizi GM, Cantalupo G, Ferrarini M, Simonati A, Dalla Bernardina B, Darra F
Seizure 2016 Nov;42:1-6. Epub 2016 Sep 5 doi: 10.1016/j.seizure.2016.08.008. PMID: 27632409

Therapy

Mir A, Alghamdi A, Alotaibi W, Samreen D, Alotaibi M, Albaradie R, Bashir S
Epileptic Disord 2022 Aug 1;24(4):633-646. doi: 10.1684/epd.2022.1439. PMID: 35770766
Trinka E, Lattanzi S, Carpenter K, Corradetti T, Nucera B, Rinaldi F, Shankar R, Brigo F
CNS Drugs 2021 Aug;35(8):821-837. Epub 2021 Jul 7 doi: 10.1007/s40263-021-00831-y. PMID: 34232492Free PMC Article
Fallah R
Indian J Pediatr 2006 Dec;73(12):1073-5. doi: 10.1007/BF02763047. PMID: 17202632
Smith B, Shatz R, Elisevich K, Bespalova IN, Burmeister M
Epilepsia 2000 Aug;41(8):1046-8. doi: 10.1111/j.1528-1157.2000.tb00293.x. PMID: 10961635
Chadwick D, Hallett M, Harris R, Jenner P, Reynolds EH, Marsden CD
Brain 1977 Sep;100(3):455-87. doi: 10.1093/brain/100.3.455. PMID: 412560

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
Atasu B, Acarlı ANO, Bilgic B, Baykan B, Demir E, Ozluk Y, Turkmen A, Hauser AK, Guven G, Hanagasi H, Gurvit H, Emre M, Gasser T, Lohmann E
BMC Neurol 2022 Mar 28;22(1):122. doi: 10.1186/s12883-022-02628-y. PMID: 35346091Free PMC Article
Opri R, Fabrizi GM, Cantalupo G, Ferrarini M, Simonati A, Dalla Bernardina B, Darra F
Seizure 2016 Nov;42:1-6. Epub 2016 Sep 5 doi: 10.1016/j.seizure.2016.08.008. PMID: 27632409
d'Orsi G, Specchio LM; Apulian Study Group on Senile Myoclonic Epilepsy
J Neurol 2014 Aug;261(8):1584-97. Epub 2014 Jun 4 doi: 10.1007/s00415-014-7376-x. PMID: 24893590
Jović NJ
Srp Arh Celok Lek 2013 Jul-Aug;141(7-8):434-40. doi: 10.2298/sarh1308434j. PMID: 24073547

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
Mir A, Alghamdi A, Alotaibi W, Samreen D, Alotaibi M, Albaradie R, Bashir S
Epileptic Disord 2022 Aug 1;24(4):633-646. doi: 10.1684/epd.2022.1439. PMID: 35770766
Rus CM, Weissensteiner T, Pereira C, Susnea I, Danquah BD, Morales Torres G, Rocha ME, Cozma C, Saravanakumar D, Mannepalli S, Kandaswamy KK, Di Bucchianico S, Zimmermann R, Rolfs A, Bauer P, Beetz C
Orphanet J Rare Dis 2022 May 3;17(1):179. doi: 10.1186/s13023-022-02288-8. PMID: 35505348Free PMC Article
Ferranti S, Lo Rizzo C, Renieri A, Galluzzi P, Grosso S
Neurol Sci 2020 Nov;41(11):3345-3348. Epub 2020 May 21 doi: 10.1007/s10072-020-04418-1. PMID: 32440981
d'Orsi G, Specchio LM; Apulian Study Group on Senile Myoclonic Epilepsy
J Neurol 2014 Aug;261(8):1584-97. Epub 2014 Jun 4 doi: 10.1007/s00415-014-7376-x. PMID: 24893590

Recent systematic reviews

Mir A, Alghamdi A, Alotaibi W, Samreen D, Alotaibi M, Albaradie R, Bashir S
Epileptic Disord 2022 Aug 1;24(4):633-646. doi: 10.1684/epd.2022.1439. PMID: 35770766
Trinka E, Lattanzi S, Carpenter K, Corradetti T, Nucera B, Rinaldi F, Shankar R, Brigo F
CNS Drugs 2021 Aug;35(8):821-837. Epub 2021 Jul 7 doi: 10.1007/s40263-021-00831-y. PMID: 34232492Free PMC Article

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