EPM3
MCID: EPL206
MIFTS: 30

Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular Inclusions (EPM3)

Categories: Eye diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular...

MalaCards integrated aliases for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular Inclusions:

Name: Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular Inclusions 57 6
Epilepsy, Progressive Myoclonic 3, with or Without Intracellular Inclusions 57 72 13
Epm3 57 58 72
Cln14 57 72
Progressive Myoclonic Epilepsy Due to Kctd7 Deficiency 58
Ceroid Lipofuscinosis, Neuronal, 14; Cln14 57
Progressive Myoclonus Epilepsy Type 3 58
Progressive Myoclonic Epilepsy Type 3 58
Ceroid Lipofuscinosis, Neuronal, 14 57
Neuronal Ceroid Lipofuscinosis 14 72
Epilepsy, Progressive Myoclonic 3 70
Progressive Myoclonic Epilepsy 3 72
Cln14 Disease 58
Pme Type 3 58

Characteristics:

Orphanet epidemiological data:

58
progressive myoclonic epilepsy type 3
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset before age 2 years
severe phenotype
two unrelated families have been reported (last curated july 2012)
only 1 family had ultrastructural cellular findings of neuronal ceroid lipofuscinosis


HPO:

31
epilepsy, progressive myoclonic, 3, with or without intracellular inclusions:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Inborn errors of metabolism


External Ids:

OMIM® 57 611726
OMIM Phenotypic Series 57 PS254800 PS256730
ICD10 via Orphanet 33 G40.3
UMLS via Orphanet 71 C2673257
Orphanet 58 ORPHA263516
MedGen 41 C2673257
UMLS 70 C2673257

Summaries for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular...

OMIM® : 57 Mutations in the KCTD7 gene cause a severe neurodegenerative phenotype characterized by onset of intractable myoclonic seizures before age 2 years and accompanied by developmental regression. The initial description was consistent with a form of progressive myoclonic epilepsy (designated here as EPM3), whereas a later report identified intracellular accumulation of autofluorescent lipopigment storage material, consistent with neuronal ceroid lipofuscinosis (designated CLN14). Ultrastructural findings on skin biopsies thus appear to be variable. However, clinical features are generally consistent between reports (summary by Staropoli et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800). For a general phenotypic description and a discussion of genetic heterogeneity of neuronal ceroid lipofuscinosis, see CLN1 (256730). (611726) (Updated 20-May-2021)

MalaCards based summary : Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular Inclusions, also known as epilepsy, progressive myoclonic 3, with or without intracellular inclusions, is related to epilepsy progressive myoclonic type 3 and progressive myoclonus epilepsy 3, and has symptoms including ataxia, truncal and myoclonic seizures. An important gene associated with Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular Inclusions is KCTD7 (Potassium Channel Tetramerization Domain Containing 7). Affiliated tissues include eye, and related phenotypes are intellectual disability and dysarthria

UniProtKB/Swiss-Prot : 72 Epilepsy, progressive myoclonic 3, with or without intracellular inclusions: An autosomal recessive, severe, progressive myoclonic epilepsy with early onset. Multifocal myoclonic seizures begin between 16 and 24 months of age after normal initial development. Neurodegeneration and regression occur with seizure onset. Other features include mental retardation, dysarthria, truncal ataxia, and loss of fine finger movements. EEG shows slow dysrhythmia, multifocal and occasionally generalized epileptiform discharges. In some patients, ultrastructural findings on skin biopsies identify intracellular accumulation of autofluorescent lipopigment storage material, consistent with neuronal ceroid lipofuscinosis.

Related Diseases for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular...

Diseases related to Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular Inclusions via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 epilepsy progressive myoclonic type 3 11.3
2 progressive myoclonus epilepsy 3 11.0

Symptoms & Phenotypes for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular...

Human phenotypes related to Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular Inclusions:

58 31 (show all 31)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
2 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
3 developmental regression 58 31 frequent (33%) Frequent (79-30%) HP:0002376
4 progressive psychomotor deterioration 58 31 frequent (33%) Frequent (79-30%) HP:0007272
5 focal eeg discharges with secondary generalization 58 31 frequent (33%) Frequent (79-30%) HP:0011188
6 progressive truncal ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0007221
7 focal myoclonic seizure 31 frequent (33%) HP:0011166
8 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
9 optic atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000648
10 abnormality of vision 58 31 occasional (7.5%) Occasional (29-5%) HP:0000504
11 aplasia/hypoplasia of the corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0007370
12 cerebellar atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001272
13 cerebral atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002059
14 dementia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000726
15 progressive cerebellar ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002073
16 chin myoclonus 58 31 occasional (7.5%) Occasional (29-5%) HP:0012462
17 limb myoclonus 58 31 occasional (7.5%) Occasional (29-5%) HP:0045084
18 hypoplasia of the corpus callosum 31 occasional (7.5%) HP:0002079
19 visual loss 31 occasional (7.5%) HP:0000572
20 bilateral tonic-clonic seizure 31 occasional (7.5%) HP:0002069
21 febrile seizure (within the age range of 3 months to 6 years) 31 occasional (7.5%) HP:0002373
22 photosensitive myoclonic seizure 31 occasional (7.5%) HP:0001327
23 myoclonus 58 Frequent (79-30%)
24 generalized tonic-clonic seizures 58 Occasional (29-5%)
25 photomyoclonic seizures 58 Occasional (29-5%)
26 truncal ataxia 31 HP:0002078
27 febrile seizures 58 Occasional (29-5%)
28 focal myoclonic seizures 58 Frequent (79-30%)
29 eeg with focal epileptiform discharges 58 Occasional (29-5%)
30 generalized myoclonic seizure 31 HP:0002123
31 fingerprint intracellular accumulation of autofluorescent lipopigment storage material 31 HP:0003208

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
dysarthria
truncal ataxia
myoclonic seizures
mental retardation
cerebellar atrophy (in 1 family)
more
Head And Neck Head:
microcephaly (in 1 family)

Laboratory Abnormalities:
'fingerprint profiles' ultrastructurally in cells
granular osmiophilic cytoplasmic deposits ultrastructurally in cells
'rectilinear profiles' ultrastructurally in cells

Head And Neck Eyes:
visual loss (in 1 family)
optic atrophy, mild (in 1 patient)

Clinical features from OMIM®:

611726 (Updated 20-May-2021)

UMLS symptoms related to Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular Inclusions:


ataxia, truncal; myoclonic seizures

Drugs & Therapeutics for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular...

Search Clinical Trials , NIH Clinical Center for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular Inclusions

Genetic Tests for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular...

Anatomical Context for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular...

MalaCards organs/tissues related to Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular Inclusions:

40
Eye

Publications for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular...

Articles related to Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular Inclusions:

# Title Authors PMID Year
1
A homozygous mutation in KCTD7 links neuronal ceroid lipofuscinosis to the ubiquitin-proteasome system. 57 6
22748208 2012
2
Novel mutations consolidate KCTD7 as a progressive myoclonus epilepsy gene. 57 6
22693283 2012
3
Mutation of a potassium channel-related gene in progressive myoclonic epilepsy. 57 6
17455289 2007
4
Pathogenic variants in KCTD7 perturb neuronal K+ fluxes and glutamine transport. 6
27742667 2016
5
Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy. 6
26795593 2016
6
[Propofol with/without N2O versus thiopentone-isoflurane in surgery of supratentorial tumors]. 6
2274208 1990
7
KCTD7 deficiency defines a distinct neurodegenerative disorder with a conserved autophagy-lysosome defect. 61
30295347 2018

Variations for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular...

ClinVar genetic disease variations for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular Inclusions:

6 (show top 50) (show all 201)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 KCTD7 NM_153033.5(KCTD7):c.529C>T (p.Arg177Cys) SNV Affects 978068 GRCh37: 7:66103878-66103878
GRCh38: 7:66638891-66638891
2 KCTD7 NM_153033.4(KCTD7):c.458G>A (p.Arg153His) SNV Uncertain significance, Affects 561040 rs765235486 GRCh37: 7:66103383-66103383
GRCh38: 7:66638396-66638396
3 KCTD7 NM_153033.4(KCTD7):c.594del (p.Ile199fs) Deletion Pathogenic 37009 rs727502785 GRCh37: 7:66103941-66103941
GRCh38: 7:66638954-66638954
4 KCTD7 NC_000007.14:g.(?_66638233)_(66639252_?)del Deletion Pathogenic 583587 GRCh37: 7:66103220-66104239
GRCh38: 7:66638233-66639252
5 KCTD7 NM_153033.4(KCTD7):c.550C>T (p.Arg184Cys) SNV Pathogenic 36926 rs387907246 GRCh37: 7:66103899-66103899
GRCh38: 7:66638912-66638912
6 KCTD7 NM_153033.5(KCTD7):c.331del (p.Leu111fs) Deletion Pathogenic 860762 GRCh37: 7:66103255-66103255
GRCh38: 7:66638268-66638268
7 KCTD7 NM_153033.4(KCTD7):c.818A>T (p.Asn273Ile) SNV Pathogenic 37011 rs387907261 GRCh37: 7:66104167-66104167
GRCh38: 7:66639180-66639180
8 KCTD7 NM_153033.4(KCTD7):c.343G>T (p.Asp115Tyr) SNV Pathogenic 37012 rs387907262 GRCh37: 7:66103268-66103268
GRCh38: 7:66638281-66638281
9 KCTD7 NM_153033.4(KCTD7):c.322C>A (p.Leu108Met) SNV Pathogenic 37013 rs387907263 GRCh37: 7:66103247-66103247
GRCh38: 7:66638260-66638260
10 KCTD7 NC_000007.14:g.(?_66629045)_(66640414_?)del Deletion Pathogenic 831752 GRCh37: 7:66094032-66105401
GRCh38:
11 KCTD7 NM_153033.4(KCTD7):c.295C>T (p.Arg99Ter) SNV Pathogenic 843 rs267607199 GRCh37: 7:66098412-66098412
GRCh38: 7:66633425-66633425
12 KCTD7 NC_000007.13:g.(?_66098242)_(66098451_?)dup Duplication Likely pathogenic 584347 GRCh37: 7:66098242-66098451
GRCh38: 7:66633255-66633464
13 KCTD7 NM_153033.4(KCTD7):c.551G>A (p.Arg184His) SNV Likely pathogenic 800962 rs747676224 GRCh37: 7:66103900-66103900
GRCh38: 7:66638913-66638913
14 KCTD7 NM_153033.4(KCTD7):c.314+1G>A SNV Likely pathogenic 536951 rs1554397834 GRCh37: 7:66098432-66098432
GRCh38: 7:66633445-66633445
15 KCTD7 NM_153033.4(KCTD7):c.145-2A>G SNV Likely pathogenic 520584 rs1554397774 GRCh37: 7:66098260-66098260
GRCh38: 7:66633273-66633273
16 KCTD7 NM_153033.4(KCTD7):c.456G>A (p.Val152=) SNV Likely pathogenic 206004 rs796052686 GRCh37: 7:66103381-66103381
GRCh38: 7:66638394-66638394
17 KCTD7 NM_153033.4(KCTD7):c.256T>C (p.Tyr86His) SNV Conflicting interpretations of pathogenicity 206012 rs149255570 GRCh37: 7:66098373-66098373
GRCh38: 7:66633386-66633386
18 KCTD7 NM_153033.4(KCTD7):c.621C>A (p.Leu207=) SNV Conflicting interpretations of pathogenicity 502314 rs376944331 GRCh37: 7:66103970-66103970
GRCh38: 7:66638983-66638983
19 KCTD7 NM_153033.4(KCTD7):c.384G>A (p.Glu128=) SNV Conflicting interpretations of pathogenicity 138057 rs145238250 GRCh37: 7:66103309-66103309
GRCh38: 7:66638322-66638322
20 KCTD7 NM_153033.4(KCTD7):c.273C>T (p.Ser91=) SNV Conflicting interpretations of pathogenicity 206008 rs139585796 GRCh37: 7:66098390-66098390
GRCh38: 7:66633403-66633403
21 KCTD7 NM_153033.4(KCTD7):c.687T>C (p.Asp229=) SNV Conflicting interpretations of pathogenicity 138054 rs372150992 GRCh37: 7:66104036-66104036
GRCh38: 7:66639049-66639049
22 KCTD7 NM_153033.4(KCTD7):c.280C>T (p.Arg94Trp) SNV Conflicting interpretations of pathogenicity 37010 rs387907260 GRCh37: 7:66098397-66098397
GRCh38: 7:66633410-66633410
23 KCTD7 NM_153033.4(KCTD7):c.335G>A (p.Arg112His) SNV Conflicting interpretations of pathogenicity 206015 rs774026720 GRCh37: 7:66103260-66103260
GRCh38: 7:66638273-66638273
24 KCTD7 NM_153033.4(KCTD7):c.533C>T (p.Ala178Val) SNV Conflicting interpretations of pathogenicity 559579 rs368001837 GRCh37: 7:66103882-66103882
GRCh38: 7:66638895-66638895
25 KCTD7 NM_153033.4(KCTD7):c.76G>T (p.Asp26Tyr) SNV Uncertain significance 206019 rs371919994 GRCh37: 7:66094127-66094127
GRCh38: 7:66629140-66629140
26 KCTD7 NM_153033.5(KCTD7):c.640C>T (p.Arg214Trp) SNV Uncertain significance 859026 GRCh37: 7:66103989-66103989
GRCh38: 7:66639002-66639002
27 KCTD7 NM_153033.5(KCTD7):c.259A>G (p.Ile87Val) SNV Uncertain significance 934736 GRCh37: 7:66098376-66098376
GRCh38: 7:66633389-66633389
28 KCTD7 NC_000007.13:g.(?_66094052)_(66104219_?)dup Duplication Uncertain significance 1016282 GRCh37: 7:66094052-66104219
GRCh38:
29 KCTD7 NM_153033.5(KCTD7):c.523C>T (p.Arg175Trp) SNV Uncertain significance 835977 GRCh37: 7:66103872-66103872
GRCh38: 7:66638885-66638885
30 KCTD7 NM_153033.5(KCTD7):c.239T>C (p.Met80Thr) SNV Uncertain significance 841460 GRCh37: 7:66098356-66098356
GRCh38: 7:66633369-66633369
31 KCTD7 NM_153033.5(KCTD7):c.209G>A (p.Arg70Gln) SNV Uncertain significance 847364 GRCh37: 7:66098326-66098326
GRCh38: 7:66633339-66633339
32 KCTD7 NM_153033.4(KCTD7):c.145T>C (p.Phe49Leu) SNV Uncertain significance 589052 rs559020294 GRCh37: 7:66098262-66098262
GRCh38: 7:66633275-66633275
33 KCTD7 NM_153033.5(KCTD7):c.188C>T (p.Thr63Ile) SNV Uncertain significance 937090 GRCh37: 7:66098305-66098305
GRCh38: 7:66633318-66633318
34 KCTD7 NM_153033.5(KCTD7):c.371C>G (p.Ala124Gly) SNV Uncertain significance 938692 GRCh37: 7:66103296-66103296
GRCh38: 7:66638309-66638309
35 KCTD7 NM_153033.5(KCTD7):c.632G>T (p.Arg211Leu) SNV Uncertain significance 939056 GRCh37: 7:66103981-66103981
GRCh38: 7:66638994-66638994
36 KCTD7 NM_153033.5(KCTD7):c.773C>A (p.Thr258Asn) SNV Uncertain significance 956498 GRCh37: 7:66104122-66104122
GRCh38: 7:66639135-66639135
37 KCTD7 NM_153033.5(KCTD7):c.636T>G (p.Phe212Leu) SNV Uncertain significance 964596 GRCh37: 7:66103985-66103985
GRCh38: 7:66638998-66638998
38 KCTD7 NM_153033.5(KCTD7):c.623A>G (p.Asn208Ser) SNV Uncertain significance 970566 GRCh37: 7:66103972-66103972
GRCh38: 7:66638985-66638985
39 KCTD7 NM_153033.5(KCTD7):c.524G>A (p.Arg175Gln) SNV Uncertain significance 908986 GRCh37: 7:66103873-66103873
GRCh38: 7:66638886-66638886
40 KCTD7 NM_153033.5(KCTD7):c.763C>G (p.Gln255Glu) SNV Uncertain significance 1027804 GRCh37: 7:66104112-66104112
GRCh38: 7:66639125-66639125
41 KCTD7 NM_153033.5(KCTD7):c.380A>G (p.Lys127Arg) SNV Uncertain significance 1039512 GRCh37: 7:66103305-66103305
GRCh38: 7:66638318-66638318
42 KCTD7 NM_153033.5(KCTD7):c.35G>T (p.Arg12Leu) SNV Uncertain significance 1039678 GRCh37: 7:66094086-66094086
GRCh38: 7:66629099-66629099
43 KCTD7 NM_153033.5(KCTD7):c.602C>G (p.Pro201Arg) SNV Uncertain significance 1041988 GRCh37: 7:66103951-66103951
GRCh38: 7:66638964-66638964
44 KCTD7 NM_153033.5(KCTD7):c.650G>A (p.Ser217Asn) SNV Uncertain significance 1042812 GRCh37: 7:66103999-66103999
GRCh38: 7:66639012-66639012
45 KCTD7 NM_153033.5(KCTD7):c.208C>T (p.Arg70Trp) SNV Uncertain significance 1046937 GRCh37: 7:66098325-66098325
GRCh38: 7:66633338-66633338
46 KCTD7 NM_153033.4(KCTD7):c.362G>T (p.Arg121Leu) SNV Uncertain significance 206020 rs199624315 GRCh37: 7:66103287-66103287
GRCh38: 7:66638300-66638300
47 KCTD7 NM_153033.4(KCTD7):c.193C>T (p.Arg65Cys) SNV Uncertain significance 206011 rs200321023 GRCh37: 7:66098310-66098310
GRCh38: 7:66633323-66633323
48 CLN3 NM_000086.2(CLN3):c.242C>T (p.Pro81Leu) SNV Uncertain significance 205105 rs137906617 GRCh37: 16:28499964-28499964
GRCh38: 16:28488643-28488643
49 KCTD7 NM_153033.4(KCTD7):c.710C>G (p.Ala237Gly) SNV Uncertain significance 662720 rs1584399776 GRCh37: 7:66104059-66104059
GRCh38: 7:66639072-66639072
50 KCTD7 NM_153033.5(KCTD7):c.251G>A (p.Arg84Gln) SNV Uncertain significance 848103 GRCh37: 7:66098368-66098368
GRCh38: 7:66633381-66633381

UniProtKB/Swiss-Prot genetic disease variations for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular Inclusions:

72
# Symbol AA change Variation ID SNP ID
1 KCTD7 p.Arg94Trp VAR_068776 rs387907260
2 KCTD7 p.Leu108Met VAR_068777 rs387907263
3 KCTD7 p.Arg184Cys VAR_068779 rs387907246
4 KCTD7 p.Asn273Ile VAR_068780 rs387907261

Expression for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular...

Search GEO for disease gene expression data for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular Inclusions.

Pathways for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular...

GO Terms for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular...

Sources for Epilepsy, Progressive Myoclonic, 3, with or Without Intracellular...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....