PNKD3
MCID: PRX090
MIFTS: 31

Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy (PNKD3)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without...

MalaCards integrated aliases for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy:

Name: Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy 57 72 29 6
Generalized Epilepsy and Paroxysmal Dyskinesia 57 72 36 13 70
Gepd 57 58 72
Pnkd3 57 72
Dyskinesia, Nonkinesigenic, Paroxysmal, Type 3, with/without Generalized Epilepsy 39
Generalized Epilepsy and Paroxysmal Dyskinesia; Gepd 57
Generalized Epilepsy-Paroxysmal Dyskinesia Syndrome 58

Characteristics:

Orphanet epidemiological data:

58
generalized epilepsy-paroxysmal dyskinesia syndrome
Inheritance: Autosomal dominant; Age of onset: Childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
de novo mutation (in some patients)
patients may have seizures only, dyskinesia only, or both
onset usually in childhood (range 6 months to 16 years)
dyskinesia may be precipitated by alcohol, stress, or fatigue


HPO:

31
paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

OMIM® 57 609446
KEGG 36 H01258
ICD10 via Orphanet 33 G40.3
UMLS via Orphanet 71 C1836173
Orphanet 58 ORPHA79137
MedGen 41 C1836173
UMLS 70 C1836173

Summaries for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without...

KEGG : 36 Epilepsy is one of the most common and debilitating neurological disorders, and paroxysmal dyskinesia is another heterogeneous group of neurological disorders characterized by sudden, unpredictable, disabling attacks of involuntary movement often requiring life-long treatment. It has been reported that a mutation of the alpha subunit of the BK channel causes a syndrome of coexistent epilepsy and paroxysmal dyskinesia, which is called generalized epilepsy and paroxysmal dyskinesia (GEPD).

MalaCards based summary : Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy, also known as generalized epilepsy and paroxysmal dyskinesia, is related to cerebellar atrophy, developmental delay, and seizures and paroxysmal dyskinesia, and has symptoms including absence seizures An important gene associated with Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy is KCNMA1 (Potassium Calcium-Activated Channel Subfamily M Alpha 1), and among its related pathways/superpathways is Vascular smooth muscle contraction. Affiliated tissues include smooth muscle, and related phenotypes are eeg with spike-wave complexes (>3.5 hz) and paroxysmal dyskinesia

UniProtKB/Swiss-Prot : 72 Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy: An autosomal dominant neurologic disorder characterized by absence seizures, generalized tonic-clonic seizures, paroxysmal nonkinesigenic dyskinesia and involuntary dystonic or choreiform movements. Onset is usually in childhood. Patients may have seizures only, dyskinesia only, or both.

More information from OMIM: 609446

Related Diseases for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without...

Diseases related to Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 cerebellar atrophy, developmental delay, and seizures 9.6 KCNMA1-AS1 KCNMA1
2 paroxysmal dyskinesia 9.6 KCNMA1-AS1 KCNMA1
3 disease of mental health 9.5 KCNMA1-AS1 KCNMA1

Symptoms & Phenotypes for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without...

Human phenotypes related to Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy:

58 31 (show all 14)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 eeg with spike-wave complexes (>3.5 hz) 58 31 frequent (33%) Frequent (79-30%) HP:0010849
2 paroxysmal dyskinesia 58 31 frequent (33%) Frequent (79-30%) HP:0007166
3 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
4 chorea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002072
5 global developmental delay 58 31 very rare (1%) Occasional (29-5%) HP:0001263
6 intellectual disability, borderline 58 31 occasional (7.5%) Occasional (29-5%) HP:0006889
7 generalized hypotonia 58 31 very rare (1%) Occasional (29-5%) HP:0001290
8 esotropia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000565
9 bilateral tonic-clonic seizure 31 occasional (7.5%) HP:0002069
10 generalized non-motor (absence) seizure 31 occasional (7.5%) HP:0002121
11 dyskinesia 31 HP:0100660
12 generalized tonic-clonic seizures 58 Occasional (29-5%)
13 generalized-onset seizure 58 Frequent (79-30%)
14 absence seizure 58 Occasional (29-5%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
delayed development (in some patients)
seizures, absence (in some patients)
seizures, generalized tonic-clonic (in some patients)
paroxysmal nonkinesigenic dyskinesia
involuntary dystonic or choreiform movements
more
Muscle Soft Tissue:
hypotonia (in some patients)

Clinical features from OMIM®:

609446 (Updated 05-Apr-2021)

UMLS symptoms related to Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy:


absence seizures

Drugs & Therapeutics for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without...

Search Clinical Trials , NIH Clinical Center for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy

Genetic Tests for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without...

Genetic tests related to Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy:

# Genetic test Affiliating Genes
1 Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy 29 KCNMA1

Anatomical Context for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without...

MalaCards organs/tissues related to Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy:

40
Smooth Muscle

Publications for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without...

Articles related to Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy:

# Title Authors PMID Year
1
Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. 61 57 6
15937479 2005
2
De novo KCNMA1 mutations in children with early-onset paroxysmal dyskinesia and developmental delay. 6 57
26195193 2015
3
De novo BK channel variant causes epilepsy by affecting voltage gating but not Ca2+ sensitivity. 6
29330545 2018
4
Early-onset absence epilepsy and paroxysmal dyskinesia. 57
12366739 2002
5
Idiopathic epilepsy and paroxysmal dyskinesia. 57
11520321 2001
6
De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurological phenotypes. 61
31152168 2019
7
An epilepsy/dyskinesia-associated mutation enhances BK channel activation by potentiating Ca2+ sensing. 61
20620873 2010
8
{beta} subunit-specific modulations of BK channel function by a mutation associated with epilepsy and dyskinesia. 61
19204046 2009

Variations for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without...

ClinVar genetic disease variations for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy:

6 (show top 50) (show all 335)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 KCNMA1-AS1 , KCNMA1 NM_001161352.2(KCNMA1):c.2824G>A (p.Glu942Lys) SNV Pathogenic 437870 rs1554966197 GRCh37: 10:78704609-78704609
GRCh38: 10:76944851-76944851
2 KCNMA1-AS1 , KCNMA1 NM_001161352.2(KCNMA1):c.2488C>T (p.Arg830Ter) SNV Pathogenic 942734 GRCh37: 10:78709121-78709121
GRCh38: 10:76949363-76949363
3 KCNMA1-AS1 , KCNMA1 NM_001161352.2(KCNMA1):c.2786del (p.Asn929fs) Deletion Pathogenic 859287 GRCh37: 10:78704647-78704647
GRCh38: 10:76944889-76944889
4 KCNMA1-AS1 , KCNMA1 NM_001161352.2(KCNMA1):c.3158A>G (p.Asn1053Ser) SNV Pathogenic 265313 rs886039469 GRCh37: 10:78651467-78651467
GRCh38: 10:76891709-76891709
5 KCNMA1 NM_001161352.2(KCNMA1):c.1301A>G (p.Asp434Gly) SNV Pathogenic 9427 rs137853333 GRCh37: 10:78850191-78850191
GRCh38: 10:77090433-77090433
6 KCNMA1 NM_001161352.2(KCNMA1):c.1054A>G (p.Thr352Ala) SNV Likely pathogenic 216948 rs863224885 GRCh37: 10:78870008-78870008
GRCh38: 10:77110250-77110250
7 KCNMA1-AS1 , KCNMA1 NM_001161352.2(KCNMA1):c.2846A>G (p.Asn949Ser) SNV Likely pathogenic 585333 rs1565091862 GRCh37: 10:78704587-78704587
GRCh38: 10:76944829-76944829
8 KCNMA1-AS1 , KCNMA1 NM_001161352.2(KCNMA1):c.3150G>A (p.Thr1050=) SNV Conflicting interpretations of pathogenicity 532955 rs75116272 GRCh37: 10:78651475-78651475
GRCh38: 10:76891717-76891717
9 KCNMA1 NM_001161352.2(KCNMA1):c.3650A>G (p.Asn1217Ser) SNV Conflicting interpretations of pathogenicity 464299 rs563967757 GRCh37: 10:78647085-78647085
GRCh38: 10:76887327-76887327
10 KCNMA1 NM_001161352.2(KCNMA1):c.3588G>A (p.Ser1196=) SNV Conflicting interpretations of pathogenicity 726009 rs75138661 GRCh37: 10:78647147-78647147
GRCh38: 10:76887389-76887389
11 KCNMA1 NM_001161352.2(KCNMA1):c.1227C>T (p.His409=) SNV Conflicting interpretations of pathogenicity 771950 rs202161397 GRCh37: 10:78850265-78850265
GRCh38: 10:77090507-77090507
12 KCNMA1-AS1 , KCNMA1 NM_001161352.2(KCNMA1):c.2946C>T (p.Ser982=) SNV Conflicting interpretations of pathogenicity 733308 rs74699271 GRCh37: 10:78674764-78674764
GRCh38: 10:76915006-76915006
13 KCNMA1 NM_001161352.2(KCNMA1):c.1056C>T (p.Thr352=) SNV Conflicting interpretations of pathogenicity 464291 rs75207686 GRCh37: 10:78870006-78870006
GRCh38: 10:77110248-77110248
14 KCNMA1 NM_001161352.2(KCNMA1):c.771C>T (p.Pro257=) SNV Conflicting interpretations of pathogenicity 464305 rs367642241 GRCh37: 10:78943216-78943216
GRCh38: 10:77183458-77183458
15 KCNMA1 NM_001161352.2(KCNMA1):c.144_146TTC[3] (p.Ser60del) Microsatellite Conflicting interpretations of pathogenicity 193228 rs751901610 GRCh37: 10:79397246-79397248
GRCh38: 10:77637488-77637490
16 KCNMA1-AS1 , KCNMA1 NM_001161352.2(KCNMA1):c.2547C>T (p.Asp849=) SNV Conflicting interpretations of pathogenicity 287045 rs147369374 GRCh37: 10:78709062-78709062
GRCh38: 10:76949304-76949304
17 KCNMA1 NM_001161352.2(KCNMA1):c.413C>T (p.Ala138Val) SNV Conflicting interpretations of pathogenicity 252505 rs144215383 GRCh37: 10:79163747-79163747
GRCh38: 10:77403989-77403989
18 KCNMA1 NM_001161352.2(KCNMA1):c.15_16insAGC (p.Gly6_Gly7insSer) Insertion Conflicting interpretations of pathogenicity 300975 rs780558929 GRCh37: 10:79397385-79397386
GRCh38: 10:77637627-77637628
19 KCNMA1-AS1 , KCNMA1 NM_001161352.2(KCNMA1):c.2398G>T (p.Asp800Tyr) SNV Conflicting interpretations of pathogenicity 623744 rs142210216 GRCh37: 10:78713645-78713645
GRCh38: 10:76953887-76953887
20 KCNMA1 NM_001161352.2(KCNMA1):c.89A>G (p.His30Arg) SNV Conflicting interpretations of pathogenicity 287558 rs200474297 GRCh37: 10:79397312-79397312
GRCh38: 10:77637554-77637554
21 KCNMA1 NM_001161352.2(KCNMA1):c.3653G>A (p.Arg1218Gln) SNV Uncertain significance 373537 rs200723995 GRCh37: 10:78647082-78647082
GRCh38: 10:76887324-76887324
22 KCNMA1 NM_001161352.2(KCNMA1):c.2122C>T (p.Arg708Trp) SNV Uncertain significance 996869 GRCh37: 10:78761309-78761309
GRCh38: 10:77001551-77001551
23 KCNMA1 NM_001161352.2(KCNMA1):c.36_38CGG[10] (p.Gly18_Gly20dup) Microsatellite Uncertain significance 841161 GRCh37: 10:79397344-79397345
GRCh38: 10:77637586-77637587
24 KCNMA1-AS1 , KCNMA1 NM_001161352.2(KCNMA1):c.2981C>T (p.Thr994Ile) SNV Uncertain significance 806523 rs768061213 GRCh37: 10:78674729-78674729
GRCh38: 10:76914971-76914971
25 KCNMA1 NM_001161352.2(KCNMA1):c.3635C>T (p.Thr1212Ile) SNV Uncertain significance 284021 rs200773083 GRCh37: 10:78647100-78647100
GRCh38: 10:76887342-76887342
26 KCNMA1-AS1 , KCNMA1 NM_001161352.2(KCNMA1):c.2806A>G (p.Thr936Ala) SNV Uncertain significance 998412 GRCh37: 10:78704627-78704627
GRCh38: 10:76944869-76944869
27 KCNMA1 NM_001161352.2(KCNMA1):c.59G>A (p.Gly20Asp) SNV Uncertain significance 999254 GRCh37: 10:79397342-79397342
GRCh38: 10:77637584-77637584
28 KCNMA1 NM_001161352.2(KCNMA1):c.385C>G (p.Gln129Glu) SNV Uncertain significance 1000311 GRCh37: 10:79163775-79163775
GRCh38: 10:77404017-77404017
29 KCNMA1 NM_001161352.2(KCNMA1):c.1534A>G (p.Ile512Val) SNV Uncertain significance 1001141 GRCh37: 10:78839298-78839298
GRCh38: 10:77079540-77079540
30 KCNMA1 NC_000010.10:g.(?_79163610)_(79397400_?)dup Duplication Uncertain significance 1003535 GRCh37: 10:79163610-79397400
GRCh38:
31 KCNMA1 NM_001161352.2(KCNMA1):c.1807A>G (p.Thr603Ala) SNV Uncertain significance 1004014 GRCh37: 10:78799338-78799338
GRCh38: 10:77039580-77039580
32 KCNMA1 NM_001161352.2(KCNMA1):c.4G>A (p.Ala2Thr) SNV Uncertain significance 1005038 GRCh37: 10:79397397-79397397
GRCh38: 10:77637639-77637639
33 KCNMA1 NM_001161352.2(KCNMA1):c.365G>C (p.Gly122Ala) SNV Uncertain significance 1006714 GRCh37: 10:79397036-79397036
GRCh38: 10:77637278-77637278
34 KCNMA1-AS1 , KCNMA1 NM_001161352.2(KCNMA1):c.3149C>T (p.Thr1050Met) SNV Uncertain significance 1006942 GRCh37: 10:78651476-78651476
GRCh38: 10:76891718-76891718
35 KCNMA1 NM_001161352.2(KCNMA1):c.1792T>G (p.Ser598Ala) SNV Uncertain significance 1006990 GRCh37: 10:78799353-78799353
GRCh38: 10:77039595-77039595
36 KCNMA1 NM_001161352.2(KCNMA1):c.2089C>T (p.Arg697Trp) SNV Uncertain significance 1008876 GRCh37: 10:78771728-78771728
GRCh38: 10:77011970-77011970
37 KCNMA1 NM_001161352.2(KCNMA1):c.3690C>A (p.Tyr1230Ter) SNV Uncertain significance 1010786 GRCh37: 10:78647045-78647045
GRCh38: 10:76887287-76887287
38 KCNMA1 NM_001161352.2(KCNMA1):c.3547G>A (p.Gly1183Ser) SNV Uncertain significance 1011015 GRCh37: 10:78647188-78647188
GRCh38: 10:76887430-76887430
39 KCNMA1 NM_001161352.2(KCNMA1):c.162_173del (p.Ser57_Ser60del) Deletion Uncertain significance 193230 rs754606765 GRCh37: 10:79397228-79397239
GRCh38: 10:77637470-77637481
40 KCNMA1 NM_001161352.2(KCNMA1):c.36_38CGG[8] (p.Gly20dup) Microsatellite Uncertain significance 193225 rs760628050 GRCh37: 10:79397344-79397345
GRCh38: 10:77637586-77637587
41 KCNMA1 NM_001161352.2(KCNMA1):c.31_51del (p.Ser11_Gly17del) Deletion Uncertain significance 464298 rs1484259264 GRCh37: 10:79397350-79397370
GRCh38: 10:77637592-77637612
42 KCNMA1 NM_001161352.2(KCNMA1):c.13_15GGC[7] (p.Gly10dup) Microsatellite Uncertain significance 532944 rs750804948 GRCh37: 10:79397370-79397371
GRCh38: 10:77637612-77637613
43 KCNMA1 NM_001161352.2(KCNMA1):c.31_48del (p.Ser11_Gly16del) Deletion Uncertain significance 567863 rs759136661 GRCh37: 10:79397353-79397370
GRCh38: 10:77637595-77637612
44 KCNMA1 NM_001161352.2(KCNMA1):c.30_56del (p.Ser11_Gly19del) Deletion Uncertain significance 655940 rs1163075445 GRCh37: 10:79397345-79397371
GRCh38: 10:77637587-77637613
45 KCNMA1 NM_001161352.2(KCNMA1):c.31_48dup (p.Ser11_Gly16dup) Duplication Uncertain significance 497141 rs759136661 GRCh37: 10:79397352-79397353
GRCh38: 10:77637594-77637595
46 KCNMA1 NM_001161352.2(KCNMA1):c.3673C>T (p.Arg1225Trp) SNV Uncertain significance 848479 GRCh37: 10:78647062-78647062
GRCh38: 10:76887304-76887304
47 KCNMA1 NM_001161352.2(KCNMA1):c.3547G>C (p.Gly1183Arg) SNV Uncertain significance 934372 GRCh37: 10:78647188-78647188
GRCh38: 10:76887430-76887430
48 KCNMA1 NM_001161352.2(KCNMA1):c.117CTC[10] (p.Ser58_Ser60dup) Microsatellite Uncertain significance 935781 GRCh37: 10:79397263-79397264
GRCh38: 10:77637505-77637506
49 KCNMA1 NM_001161352.2(KCNMA1):c.117CTC[9] (p.Ser59_Ser60dup) Microsatellite Uncertain significance 938883 GRCh37: 10:79397263-79397264
GRCh38: 10:77637505-77637506
50 KCNMA1 NM_001161352.2(KCNMA1):c.36_65del (p.Gly13_Ser22del) Deletion Uncertain significance 942877 GRCh37: 10:79397336-79397365
GRCh38: 10:77637578-77637607

UniProtKB/Swiss-Prot genetic disease variations for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy:

72
# Symbol AA change Variation ID SNP ID
1 KCNMA1 p.Asp434Gly VAR_023821 rs137853333
2 KCNMA1 p.Glu884Lys VAR_079156
3 KCNMA1 p.Asn1053Ser VAR_079157 rs886039469

Expression for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without...

Search GEO for disease gene expression data for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy.

Pathways for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without...

Pathways related to Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without Generalized Epilepsy according to KEGG:

36
# Name Kegg Source Accession
1 Vascular smooth muscle contraction hsa04270

GO Terms for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without...

Sources for Paroxysmal Nonkinesigenic Dyskinesia, 3, with or Without...

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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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