AHC2
MCID: ALT007
MIFTS: 30

Alternating Hemiplegia of Childhood 2 (AHC2)

Categories: Eye diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Alternating Hemiplegia of Childhood 2

MalaCards integrated aliases for Alternating Hemiplegia of Childhood 2:

Name: Alternating Hemiplegia of Childhood 2 57 72 29 13 6 70
Ahc2 57 72
Hemiplegia, Alternating, of Childhood, Type 2 39

Characteristics:

OMIM®:

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

Miscellaneous:
onset before 18 months of age
variable severity and progression
abrupt onset of episodes
episodes may be triggered by physical or emotional stress
flunarizine treatment may be beneficial
most cases due to de novo mutation


HPO:

31
alternating hemiplegia of childhood 2:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM® 57 614820
OMIM Phenotypic Series 57 PS104290
MeSH 44 D006429
UMLS 70 C3553788

Summaries for Alternating Hemiplegia of Childhood 2

UniProtKB/Swiss-Prot : 72 Alternating hemiplegia of childhood 2: A rare syndrome of episodic hemi- or quadriplegia lasting minutes to days. Most cases are accompanied by dystonic posturing, choreoathetoid movements, nystagmus, other ocular motor abnormalities, autonomic disturbances, and progressive cognitive impairment. It is typically distinguished from familial hemiplegic migraine by infantile onset and high prevalence of associated neurological deficits that become increasingly obvious with age.

MalaCards based summary : Alternating Hemiplegia of Childhood 2, also known as ahc2, is related to alternating hemiplegia of childhood and mild cognitive impairment, and has symptoms including seizures and ataxia. An important gene associated with Alternating Hemiplegia of Childhood 2 is ATP1A3 (ATPase Na+/K+ Transporting Subunit Alpha 3). Affiliated tissues include eye, and related phenotypes are intellectual disability and nystagmus

OMIM® : 57 Alternating hemiplegia of childhood is a rare syndrome characterized by infantile onset of episodic hemi-or quadriplegia. Most cases are accompanied by dystonic posturing, choreoathetoid movements, abnormal ocular movements, developmental delay, and progressive cognitive impairment (summary by Heinzen et al., 2012). For a discussion of genetic heterogeneity of alternating hemiplegia of childhood, see AHC1 (104290). (614820) (Updated 20-May-2021)

Related Diseases for Alternating Hemiplegia of Childhood 2

Diseases in the Alternating Hemiplegia of Childhood family:

Alternating Hemiplegia of Childhood 1 Alternating Hemiplegia of Childhood 2

Diseases related to Alternating Hemiplegia of Childhood 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 alternating hemiplegia of childhood 10.1
2 mild cognitive impairment 10.1
3 hemiplegia 10.1
4 dystonia 10.1
5 encephalopathy 10.1

Graphical network of the top 20 diseases related to Alternating Hemiplegia of Childhood 2:



Diseases related to Alternating Hemiplegia of Childhood 2

Symptoms & Phenotypes for Alternating Hemiplegia of Childhood 2

Human phenotypes related to Alternating Hemiplegia of Childhood 2:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 nystagmus 31 HP:0000639
3 ataxia 31 HP:0001251
4 dysarthria 31 HP:0001260
5 global developmental delay 31 HP:0001263
6 mental deterioration 31 HP:0001268
7 dystonia 31 HP:0001332
8 status epilepticus 31 HP:0002133
9 choreoathetosis 31 HP:0001266
10 hemiplegia 31 HP:0002301
11 episodic quadriplegia 31 HP:0200072

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
intellectual disability
seizures
ataxia
dysarthria
dystonia
more
Respiratory:
respiratory disturbances

Head And Neck Eyes:
nystagmus
abnormal extraocular movements

Clinical features from OMIM®:

614820 (Updated 20-May-2021)

UMLS symptoms related to Alternating Hemiplegia of Childhood 2:


seizures; ataxia

Drugs & Therapeutics for Alternating Hemiplegia of Childhood 2

Search Clinical Trials , NIH Clinical Center for Alternating Hemiplegia of Childhood 2

Genetic Tests for Alternating Hemiplegia of Childhood 2

Genetic tests related to Alternating Hemiplegia of Childhood 2:

# Genetic test Affiliating Genes
1 Alternating Hemiplegia of Childhood 2 29 ATP1A3

Anatomical Context for Alternating Hemiplegia of Childhood 2

MalaCards organs/tissues related to Alternating Hemiplegia of Childhood 2:

40
Eye

Publications for Alternating Hemiplegia of Childhood 2

Articles related to Alternating Hemiplegia of Childhood 2:

(show all 21)
# Title Authors PMID Year
1
ATP1A3 mutations and genotype-phenotype correlation of alternating hemiplegia of childhood in Chinese patients. 57 6
24842602 2014
2
De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. 57 6
22842232 2012
3
Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study. 57 6
22850527 2012
4
Clinical profile of patients with ATP1A3 mutations in Alternating Hemiplegia of Childhood-a study of 155 patients. 57 61
26410222 2015
5
Cardiac phenotype in ATP1A3-related syndromes: A multicenter cohort study. 57
32913013 2020
6
A three-year follow-up study evaluating clinical utility of exome sequencing and diagnostic potential of reanalysis. 6
32963807 2020
7
Mosaicism in ATP1A3-related disorders: not just a theoretical risk. 6
27726050 2017
8
A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders. 6
26938784 2016
9
Childhood-onset ATP1A3-related conditions: Report of two new cases of phenotypic spectrum. 6
27268479 2016
10
De novo p.Arg756Cys mutation of ATP1A3 causes an atypical form of alternating hemiplegia of childhood with prolonged paralysis and choreoathetosis. 6
27634470 2016
11
Molecular diagnostic experience of whole-exome sequencing in adult patients. 6
26633545 2016
12
Relapsing encephalopathy with cerebellar ataxia related to an ATP1A3 mutation. 6
26400718 2015
13
Alternating Hemiplegia of Childhood mutations have a differential effect on Na(+),K(+)-ATPase activity and ouabain binding. 6
24631656 2014
14
Genotype-phenotype correlations in alternating hemiplegia of childhood. 57
24431296 2014
15
Identification of ATP1A3 mutations by exome sequencing as the cause of alternating hemiplegia of childhood in Japanese patients. 6
23409136 2013
16
Rapid-onset dystonia-parkinsonism in a child with a novel atp1a3 gene mutation. 6
19652145 2009
17
Mutations in the Na+/K+ -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. 6
15260953 2004
18
Alternating hemiplegia in childhood: a report of eight patients with complicated migraine beginning in infancy. 57
5089756 1971
19
Long-term follow-up and novel genotype-phenotype analysis of monozygotic twins with ATP1A3 mutation in Alternating Hemiplegia of Childhood-2. 61
32454213 2020
20
Combinatorial depletion analysis to assemble the network architecture of the SAGA and ADA chromatin remodeling complexes. 61
21734642 2011
21
Transcriptional activators in yeast. 61
16464826 2006

Variations for Alternating Hemiplegia of Childhood 2

ClinVar genetic disease variations for Alternating Hemiplegia of Childhood 2:

6 (show top 50) (show all 129)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ATP1A3 NM_152296.5(ATP1A3):c.2512_2516delinsTC (p.Arg838_Leu839delinsSer) Indel Pathogenic 369662 rs1057516032 GRCh37: 19:42474363-42474367
GRCh38: 19:41970211-41970215
2 ATP1A3 NM_152296.5(ATP1A3):c.2767G>A (p.Asp923Asn) SNV Pathogenic 12915 rs267606670 GRCh37: 19:42472989-42472989
GRCh38: 19:41968837-41968837
3 ATP1A3 NM_152296.5(ATP1A3):c.2401G>A (p.Asp801Asn) SNV Pathogenic 37107 GRCh37: 19:42474557-42474557
GRCh38: 19:41970405-41970405
4 ATP1A3 NM_152296.5(ATP1A3):c.2443G>A (p.Glu815Lys) SNV Pathogenic 37108 rs387907281 GRCh37: 19:42474436-42474436
GRCh38: 19:41970284-41970284
5 ATP1A3 NM_152296.5(ATP1A3):c.2431T>C (p.Ser811Pro) SNV Pathogenic 37109 rs387907282 GRCh37: 19:42474448-42474448
GRCh38: 19:41970296-41970296
6 ATP1A3 NM_152296.5(ATP1A3):c.2839G>A (p.Gly947Arg) SNV Pathogenic 37110 rs398122887 GRCh37: 19:42471896-42471896
GRCh38: 19:41967744-41967744
7 ATP1A3 NM_152296.5(ATP1A3):c.2839G>C (p.Gly947Arg) SNV Pathogenic 139579 rs398122887 GRCh37: 19:42471896-42471896
GRCh38: 19:41967744-41967744
8 ATP1A3 NM_152296.5(ATP1A3):c.1003A>C (p.Thr335Pro) SNV Pathogenic 161128 rs606231431 GRCh37: 19:42486249-42486249
GRCh38: 19:41982097-41982097
9 ATP1A3 NM_152296.5(ATP1A3):c.1072G>T (p.Gly358Cys) SNV Pathogenic 161129 rs606231432 GRCh37: 19:42486180-42486180
GRCh38: 19:41982028-41982028
10 ATP1A3 NM_152296.5(ATP1A3):c.1112T>C (p.Leu371Pro) SNV Pathogenic 161130 rs606231433 GRCh37: 19:42486140-42486140
GRCh38: 19:41981988-41981988
11 ATP1A3 NM_152296.5(ATP1A3):c.2264G>C (p.Gly755Ala) SNV Pathogenic 161131 rs606231434 GRCh37: 19:42474694-42474694
GRCh38: 19:41970542-41970542
12 ATP1A3 NM_152296.5(ATP1A3):c.2263G>A (p.Gly755Ser) SNV Pathogenic 161132 rs557052809 GRCh37: 19:42479781-42479781
GRCh38: 19:41975629-41975629
13 ATP1A3 NM_152296.5(ATP1A3):c.2263G>T (p.Gly755Cys) SNV Pathogenic 161133 rs557052809 GRCh37: 19:42479781-42479781
GRCh38: 19:41975629-41975629
14 ATP1A3 NM_152296.5(ATP1A3):c.2270T>C (p.Leu757Pro) SNV Pathogenic 161135 rs606231436 GRCh37: 19:42474688-42474688
GRCh38: 19:41970536-41970536
15 ATP1A3 NM_152296.5(ATP1A3):c.2312C>A (p.Thr771Asn) SNV Pathogenic 161136 rs557939077 GRCh37: 19:42474646-42474646
GRCh38: 19:41970494-41970494
16 ATP1A3 NM_152296.5(ATP1A3):c.2316C>A (p.Ser772Arg) SNV Pathogenic 161137 rs534926223 GRCh37: 19:42474642-42474642
GRCh38: 19:41970490-41970490
17 ATP1A3 NM_152296.5(ATP1A3):c.2318A>G (p.Asn773Ser) SNV Pathogenic 161138 rs606231437 GRCh37: 19:42474640-42474640
GRCh38: 19:41970488-41970488
18 ATP1A3 NM_152296.5(ATP1A3):c.2318A>T (p.Asn773Ile) SNV Pathogenic 161139 rs606231437 GRCh37: 19:42474640-42474640
GRCh38: 19:41970488-41970488
19 ATP1A3 NM_152296.5(ATP1A3):c.2411C>T (p.Thr804Ile) SNV Pathogenic 161140 rs606231438 GRCh37: 19:42474547-42474547
GRCh38: 19:41970395-41970395
20 ATP1A3 NM_152296.5(ATP1A3):c.2415C>G (p.Asp805Glu) SNV Pathogenic 161141 rs606231439 GRCh37: 19:42474543-42474543
GRCh38: 19:41970391-41970391
21 ATP1A3 NM_152296.5(ATP1A3):c.2417T>G (p.Met806Arg) SNV Pathogenic 161142 rs549006436 GRCh37: 19:42474541-42474541
GRCh38: 19:41970389-41970389
22 ATP1A3 NM_152296.5(ATP1A3):c.2428A>T (p.Ile810Phe) SNV Pathogenic 161143 rs606231440 GRCh37: 19:42474451-42474451
GRCh38: 19:41970299-41970299
23 ATP1A3 NM_152296.5(ATP1A3):c.2429T>G (p.Ile810Ser) SNV Pathogenic 161144 rs536681257 GRCh37: 19:42474450-42474450
GRCh38: 19:41970298-41970298
24 ATP1A3 NM_152296.5(ATP1A3):c.2600G>A (p.Gly867Asp) SNV Pathogenic 161146 rs606231442 GRCh37: 19:42473675-42473675
GRCh38: 19:41969523-41969523
25 ATP1A3 NM_152296.5(ATP1A3):c.2752_2754GTC[1] (p.Val919del) Microsatellite Pathogenic 161147 rs606231443 GRCh37: 19:42472999-42473001
GRCh38: 19:41968847-41968849
26 ATP1A3 NM_152296.5(ATP1A3):c.2780G>A (p.Cys927Tyr) SNV Pathogenic 161149 rs606231444 GRCh37: 19:42472976-42472976
GRCh38: 19:41968824-41968824
27 ATP1A3 NM_152296.5(ATP1A3):c.2780G>T (p.Cys927Phe) SNV Pathogenic 161150 rs606231444 GRCh37: 19:42472976-42472976
GRCh38: 19:41968824-41968824
28 ATP1A3 NM_152296.5(ATP1A3):c.2864C>A (p.Ala955Asp) SNV Pathogenic 161152 rs606231446 GRCh37: 19:42471871-42471871
GRCh38: 19:41967719-41967719
29 ATP1A3 NM_152296.5(ATP1A3):c.2974G>T (p.Asp992Tyr) SNV Pathogenic 161153 rs606231447 GRCh37: 19:42471440-42471440
GRCh38: 19:41967288-41967288
30 ATP1A3 NM_152296.5(ATP1A3):c.2401G>A (p.Asp801Asn) SNV Pathogenic 37107 GRCh37: 19:42474557-42474557
GRCh38: 19:41970405-41970405
31 ATP1A3 NM_152296.5(ATP1A3):c.2267G>A (p.Arg756His) SNV Pathogenic 161134 rs606231435 GRCh37: 19:42474691-42474691
GRCh38: 19:41970539-41970539
32 ATP1A3 NM_152296.5(ATP1A3):c.2839G>A (p.Gly947Arg) SNV Pathogenic 37110 rs398122887 GRCh37: 19:42471896-42471896
GRCh38: 19:41967744-41967744
33 ATP1A3 NM_152296.5(ATP1A3):c.2443G>A (p.Glu815Lys) SNV Pathogenic 37108 rs387907281 GRCh37: 19:42474436-42474436
GRCh38: 19:41970284-41970284
34 ATP1A3 NM_152296.5(ATP1A3):c.1838C>T (p.Thr613Met) SNV Pathogenic 12909 GRCh37: 19:42482193-42482193
GRCh38: 19:41978041-41978041
35 ATP1A3 NM_152296.5(ATP1A3):c.998G>T (p.Cys333Phe) SNV Pathogenic 161127 rs606231430 GRCh37: 19:42486254-42486254
GRCh38: 19:41982102-41982102
36 ATP1A3 NM_152296.5(ATP1A3):c.965T>A (p.Val322Asp) SNV Pathogenic 161125 rs606231428 GRCh37: 19:42489098-42489098
GRCh38: 19:41984946-41984946
37 ATP1A3 NM_152296.5(ATP1A3):c.821T>A (p.Ile274Asn) SNV Pathogenic 161124 rs80356532 GRCh37: 19:42489242-42489242
GRCh38: 19:41985090-41985090
38 ATP1A3 NM_152296.5(ATP1A3):c.419A>T (p.Gln140Leu) SNV Pathogenic 161123 rs606231427 GRCh37: 19:42490320-42490320
GRCh38: 19:41986168-41986168
39 ATP1A3 NM_152296.5(ATP1A3):c.410C>T (p.Ser137Phe) SNV Pathogenic 161122 rs542652468 GRCh37: 19:42490329-42490329
GRCh38: 19:41986177-41986177
40 ATP1A3 NM_152296.5(ATP1A3):c.410C>A (p.Ser137Tyr) SNV Pathogenic 161121 rs542652468 GRCh37: 19:42490329-42490329
GRCh38: 19:41986177-41986177
41 ATP1A3 NM_152296.5(ATP1A3):c.954C>G (p.Ile318Met) SNV Pathogenic 929469 GRCh37: 19:42489109-42489109
GRCh38: 19:41984957-41984957
42 ATP1A3 NM_152296.5(ATP1A3):c.2116G>A (p.Gly706Arg) SNV Pathogenic 372799 rs782175860 GRCh37: 19:42479928-42479928
GRCh38: 19:41975776-41975776
43 ATP1A3 NM_152296.5(ATP1A3):c.2781C>G (p.Cys927Trp) SNV Pathogenic 161151 rs606231445 GRCh37: 19:42472975-42472975
GRCh38: 19:41968823-41968823
44 ATP1A3 NM_152296.5(ATP1A3):c.2767G>T (p.Asp923Tyr) SNV Pathogenic 161148 rs267606670 GRCh37: 19:42472989-42472989
GRCh38: 19:41968837-41968837
45 ATP1A3 NM_152296.5(ATP1A3):c.2542+1G>A SNV Pathogenic 161145 rs606231441 GRCh37: 19:42474336-42474336
GRCh38: 19:41970184-41970184
46 ATP1A3 NM_152296.5(ATP1A3):c.2767G>A (p.Asp923Asn) SNV Pathogenic 12915 rs267606670 GRCh37: 19:42472989-42472989
GRCh38: 19:41968837-41968837
47 ATP1A3 NM_152296.5(ATP1A3):c.2452G>A (p.Glu818Lys) SNV Pathogenic 156238 rs587777771 GRCh37: 19:42474427-42474427
GRCh38: 19:41970275-41970275
48 ATP1A3 NM_152296.5(ATP1A3):c.1090T>C (p.Cys364Arg) SNV Likely pathogenic 981160 GRCh37: 19:42486162-42486162
GRCh38: 19:41982010-41982010
49 ATP1A3 NM_152296.5(ATP1A3):c.2759A>G (p.Gln920Arg) SNV Likely pathogenic 1029189 GRCh37: 19:42472997-42472997
GRCh38: 19:41968845-41968845
50 ATP1A3 NM_152296.5(ATP1A3):c.1801A>R (p.Ile601Xaa) SNV Likely pathogenic 813746 GRCh37: 19:42482308-42482308
GRCh38: 19:41978156-41978156

UniProtKB/Swiss-Prot genetic disease variations for Alternating Hemiplegia of Childhood 2:

72 (show all 23)
# Symbol AA change Variation ID SNP ID
1 ATP1A3 p.Ser137Phe VAR_068935 rs542652468
2 ATP1A3 p.Ser137Tyr VAR_068936 rs542652468
3 ATP1A3 p.Gln140Leu VAR_068937 rs606231427
4 ATP1A3 p.Asp220Asn VAR_068938 rs139689846
5 ATP1A3 p.Ile274Asn VAR_068939 rs80356532
6 ATP1A3 p.Cys333Phe VAR_068940 rs606231430
7 ATP1A3 p.Gly755Ser VAR_068941 rs557052809
8 ATP1A3 p.Asn773Ser VAR_068942 rs606231437
9 ATP1A3 p.Asp801Asn VAR_068943 rs80356537
10 ATP1A3 p.Met806Arg VAR_068944 rs549006436
11 ATP1A3 p.Ile810Ser VAR_068945 rs536681257
12 ATP1A3 p.Ser811Pro VAR_068946 rs387907282
13 ATP1A3 p.Glu815Lys VAR_068947 rs387907281
14 ATP1A3 p.Gly947Arg VAR_068950 rs398122887
15 ATP1A3 p.Ala955Asp VAR_068951 rs606231446
16 ATP1A3 p.Asp992Tyr VAR_068952 rs606231447
17 ATP1A3 p.Val322Asp VAR_070767 rs606231428
18 ATP1A3 p.Leu371Pro VAR_070768 rs606231433
19 ATP1A3 p.Gly755Cys VAR_070769 rs557052809
20 ATP1A3 p.Ser772Arg VAR_070770 rs534926223
21 ATP1A3 p.Asn773Ile VAR_070771 rs606231437
22 ATP1A3 p.Asp923Tyr VAR_070773 rs267606670
23 ATP1A3 p.Cys927Tyr VAR_070774 rs606231444

Expression for Alternating Hemiplegia of Childhood 2

Search GEO for disease gene expression data for Alternating Hemiplegia of Childhood 2.

Pathways for Alternating Hemiplegia of Childhood 2

GO Terms for Alternating Hemiplegia of Childhood 2

Sources for Alternating Hemiplegia of Childhood 2

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
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35 IUPHAR
36 KEGG
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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
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