DYT28
MCID: DYS190
MIFTS: 26

Dystonia 28, Childhood-Onset (DYT28)

Categories: Genetic diseases

Aliases & Classifications for Dystonia 28, Childhood-Onset

MalaCards integrated aliases for Dystonia 28, Childhood-Onset:

Name: Dystonia 28, Childhood-Onset 57 72 29 6 17
Dyt28 57 72
Dystonia, Type 28, Childhood-Onset 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
incomplete penetrance
progressive disorder
onset in first decade
most mutations occur de novo
onset usually in lower limbs or feet
favorable response to deep brain stimulation

Inheritance:
autosomal dominant


HPO:

31
dystonia 28, childhood-onset:
Inheritance autosomal dominant inheritance
Onset and clinical course progressive incomplete penetrance


Classifications:



Summaries for Dystonia 28, Childhood-Onset

OMIM® : 57 Dystonia-28 is an autosomal dominant neurologic disorder characterized by onset of progressive dystonia in the first decade of life. Dystonia typically begins focally in the lower limbs, resulting in gait difficulties, with later progression to other body regions, including the upper limbs, neck, and orofacial region. The severity is variable, and some patients may become wheelchair-bound. Many patients also have an elongated face with bulbous nose, and some have abnormal eye movements. About half of patients show delayed motor and/or cognitive development with mild intellectual disability (summary by Zech et al., 2016 and Meyer et al., 2017). (617284) (Updated 05-Apr-2021)

MalaCards based summary : Dystonia 28, Childhood-Onset, also known as dyt28, is related to kmt2b-related dystonia and dystonia. An important gene associated with Dystonia 28, Childhood-Onset is KMT2B (Lysine Methyltransferase 2B). Affiliated tissues include eye and brain, and related phenotypes are spasticity and abnormality of eye movement

UniProtKB/Swiss-Prot : 72 Dystonia 28, childhood-onset: A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT28 is an autosomal dominant, progressive form characterized by onset in the first decade of life and variable severity. Dystonia begins focally in the lower limbs, resulting in gait difficulties, with later progression to other body regions, including the upper limbs, neck, and orofacial region.

Related Diseases for Dystonia 28, Childhood-Onset

Diseases related to Dystonia 28, Childhood-Onset via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 kmt2b-related dystonia 11.2
2 dystonia 10.0

Symptoms & Phenotypes for Dystonia 28, Childhood-Onset

Human phenotypes related to Dystonia 28, Childhood-Onset:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 spasticity 31 occasional (7.5%) HP:0001257
2 abnormality of eye movement 31 occasional (7.5%) HP:0000496
3 global developmental delay 31 occasional (7.5%) HP:0001263
4 microcephaly 31 occasional (7.5%) HP:0000252
5 short stature 31 occasional (7.5%) HP:0004322
6 cognitive impairment 31 occasional (7.5%) HP:0100543
7 myoclonus 31 occasional (7.5%) HP:0001336
8 motor delay 31 occasional (7.5%) HP:0001270
9 astigmatism 31 occasional (7.5%) HP:0000483
10 dysarthria 31 HP:0001260
11 toe walking 31 HP:0040083
12 bulbous nose 31 HP:0000414
13 laryngeal dystonia 31 HP:0012049
14 oromandibular dystonia 31 HP:0012048
15 retrocollis 31 HP:0002544

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
dysarthria
toe walking
spasticity (in some patients)
gait difficulties
cognitive impairment (in some patients)
more
Head And Neck Neck:
torticollis
retrocollis
neck dystonia

Head And Neck Mouth:
oromandibular dystonia

Growth Height:
short stature (in some patients)

Head And Neck Nose:
bulbous nasal tip

Growth Other:
poor overall growth (in some patients)

Skeletal Feet:
foot dystonia
abnormal foot posturing

Voice:
dysphonia

Respiratory Larynx:
laryngeal dystonia

Head And Neck Face:
facial dystonia
elongated face

Head And Neck Head:
microcephaly (in some patients)

Head And Neck Eyes:
astigmatism (in some patients)
eye movement abnormalities (in some patients)

Abdomen Gastrointestinal:
difficulties chewing
difficulties swallowing

Clinical features from OMIM®:

617284 (Updated 05-Apr-2021)

Drugs & Therapeutics for Dystonia 28, Childhood-Onset

Search Clinical Trials , NIH Clinical Center for Dystonia 28, Childhood-Onset

Genetic Tests for Dystonia 28, Childhood-Onset

Genetic tests related to Dystonia 28, Childhood-Onset:

# Genetic test Affiliating Genes
1 Dystonia 28, Childhood-Onset 29 KMT2B

Anatomical Context for Dystonia 28, Childhood-Onset

MalaCards organs/tissues related to Dystonia 28, Childhood-Onset:

40
Eye, Brain

Publications for Dystonia 28, Childhood-Onset

Articles related to Dystonia 28, Childhood-Onset:

# Title Authors PMID Year
1
Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia. 6 57
27992417 2017
2
Haploinsufficiency of KMT2B, Encoding the Lysine-Specific Histone Methyltransferase 2B, Results in Early-Onset Generalized Dystonia. 57 6
27839873 2016
3
KMT2B rare missense variants in generalized dystonia. 6
28520167 2017
4
KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation. 61
33150406 2020
5
A severe case of status dystonicus caused by a de novo KMT2B missense mutation. 61
32877735 2020
6
DYT28 Responsive to Pallidal Deep Brain Stimulation. 61
31970221 2020
7
Pallidal Deep Brain Stimulation for Monogenic Dystonia: The Effect of Gene on Outcome. 61
33488508 2020
8
Generalized dystonia associated with mutation in the histone methyltransferase gene KMT2B (DYT28) and white matter abnormalities. 61
29396090 2018
9
Review of the phenotype of early-onset generalised progressive dystonia due to mutations in KMT2B. 61
29289525 2018

Variations for Dystonia 28, Childhood-Onset

ClinVar genetic disease variations for Dystonia 28, Childhood-Onset:

6 (show all 43)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 KMT2B NM_014727.2(KMT2B):c.402dup (p.Ser135fs) Duplication Pathogenic 374874 rs1057519282 GRCh37: 19:36210404-36210405
GRCh38: 19:35719502-35719503
2 KMT2B NM_014727.3(KMT2B):c.118del (p.Ala40fs) Deletion Pathogenic 870575 GRCh37: 19:36209035-36209035
GRCh38: 19:35718133-35718133
3 KMT2B NM_014727.2(KMT2B):c.7050-2A>G SNV Pathogenic 374872 rs1057519280 GRCh37: 19:36224662-36224662
GRCh38: 19:35733761-35733761
4 KMT2B NM_014727.2(KMT2B):c.6406del (p.Leu2136fs) Deletion Pathogenic 374870 rs1057519278 GRCh37: 19:36223856-36223856
GRCh38: 19:35732955-35732955
5 KMT2B NM_014727.2(KMT2B):c.521dup (p.Thr176fs) Duplication Pathogenic 488539 rs763183959 GRCh37: 19:36210763-36210764
GRCh38: 19:35719861-35719862
6 KMT2B NM_014727.3(KMT2B):c.424C>T (p.Arg142Ter) SNV Pathogenic 807435 rs748888652 GRCh37: 19:36210431-36210431
GRCh38: 19:35719529-35719529
7 KMT2B NM_014727.3(KMT2B):c.3596dup (p.Met1202fs) Duplication Pathogenic 988727 GRCh37: 19:36216183-36216184
GRCh38: 19:35725282-35725283
8 KMT2B NM_014727.3(KMT2B):c.4549C>T (p.Arg1517Ter) SNV Pathogenic 807438 rs1459799356 GRCh37: 19:36219050-36219050
GRCh38: 19:35728149-35728149
9 KMT2B NM_014727.2(KMT2B):c.4622C>T (p.Ala1541Val) SNV Pathogenic 590880 rs1568377293 GRCh37: 19:36219725-36219725
GRCh38: 19:35728824-35728824
10 KMT2B NM_014727.2(KMT2B):c.5336G>A (p.Arg1779Gln) SNV Pathogenic 590881 rs779863547 GRCh37: 19:36221667-36221667
GRCh38: 19:35730766-35730766
11 KMT2B NM_014727.3(KMT2B):c.3335-9_3363del Deletion Pathogenic 976707 GRCh37: 19:36215529-36215566
GRCh38: 19:35724628-35724665
12 KMT2B NM_014727.2(KMT2B):c.12_24dup (p.Ser9fs) Duplication Pathogenic 450816 rs1555727493 GRCh37: 19:36208922-36208923
GRCh38: 19:35718020-35718021
13 KMT2B NM_014727.2(KMT2B):c.1633C>T (p.Arg545Ter) SNV Pathogenic/Likely pathogenic 374871 rs1057519279 GRCh37: 19:36211882-36211882
GRCh38: 19:35720980-35720980
14 KMT2B NM_014727.2(KMT2B):c.1690C>T (p.Arg564Ter) SNV Pathogenic/Likely pathogenic 374875 rs1057519283 GRCh37: 19:36211939-36211939
GRCh38: 19:35721037-35721037
15 KMT2B NM_014727.2(KMT2B):c.2428C>T (p.Gln810Ter) SNV Likely pathogenic 374873 rs1057519281 GRCh37: 19:36212677-36212677
GRCh38: 19:35721775-35721775
16 KMT2B NM_014727.2(KMT2B):c.4545C>A (p.Tyr1515Ter) SNV Likely pathogenic 374876 rs1057519284 GRCh37: 19:36219046-36219046
GRCh38: 19:35728145-35728145
17 KMT2B NM_014727.2(KMT2B):c.4931G>T (p.Cys1644Phe) SNV Likely pathogenic 522861 rs1555731819 GRCh37: 19:36220881-36220881
GRCh38: 19:35729980-35729980
18 KMT2B NM_014727.2(KMT2B):c.5335C>T (p.Arg1779Ter) SNV Likely pathogenic 562212 rs1568379151 GRCh37: 19:36221666-36221666
GRCh38: 19:35730765-35730765
19 KMT2B NM_014727.2(KMT2B):c.4960T>C (p.Cys1654Arg) SNV Likely pathogenic 692033 rs1599689373 GRCh37: 19:36220910-36220910
GRCh38: 19:35730009-35730009
20 KMT2B NM_014727.3(KMT2B):c.4847C>T (p.Ala1616Val) SNV Likely pathogenic 807439 rs1599687853 GRCh37: 19:36220127-36220127
GRCh38: 19:35729226-35729226
21 KMT2B NM_014727.3(KMT2B):c.3632G>A (p.Gly1211Glu) SNV Likely pathogenic 807436 rs1599679995 GRCh37: 19:36216224-36216224
GRCh38: 19:35725323-35725323
22 KMT2B NM_014727.3(KMT2B):c.3700G>A (p.Glu1234Lys) SNV Likely pathogenic 807437 rs1599680351 GRCh37: 19:36216437-36216437
GRCh38: 19:35725536-35725536
23 KMT2B NM_014727.3(KMT2B):c.1205del (p.Pro402fs) Deletion Likely pathogenic 974897 GRCh37: 19:36211453-36211453
GRCh38: 19:35720551-35720551
24 KMT2B NM_014727.3(KMT2B):c.145C>A (p.Arg49Ser) SNV Uncertain significance 1031291 GRCh37: 19:36209065-36209065
GRCh38: 19:35718163-35718163
25 KMT2B NM_014727.3(KMT2B):c.2003C>T (p.Pro668Leu) SNV Uncertain significance 1031292 GRCh37: 19:36212252-36212252
GRCh38: 19:35721350-35721350
26 KMT2B NM_014727.3(KMT2B):c.278G>C (p.Arg93Pro) SNV Uncertain significance 1031293 GRCh37: 19:36209198-36209198
GRCh38: 19:35718296-35718296
27 KMT2B NM_014727.3(KMT2B):c.5974G>T (p.Asp1992Tyr) SNV Uncertain significance 1031294 GRCh37: 19:36223424-36223424
GRCh38: 19:35732523-35732523
28 KMT2B NM_014727.3(KMT2B):c.6919T>C (p.Ser2307Pro) SNV Uncertain significance 1031295 GRCh37: 19:36224369-36224369
GRCh38: 19:35733468-35733468
29 KMT2B NM_014727.3(KMT2B):c.1028G>A (p.Arg343Lys) SNV Uncertain significance 871234 GRCh37: 19:36211277-36211277
GRCh38: 19:35720375-35720375
30 KMT2B NM_014727.3(KMT2B):c.4762G>A (p.Gly1588Arg) SNV Uncertain significance 1031843 GRCh37: 19:36219960-36219960
GRCh38: 19:35729059-35729059
31 KMT2B NM_014727.3(KMT2B):c.5006C>T (p.Ala1669Val) SNV Uncertain significance 1031844 GRCh37: 19:36220956-36220956
GRCh38: 19:35730055-35730055
32 KMT2B NM_014727.2(KMT2B):c.7549C>T (p.Arg2517Trp) SNV Uncertain significance 374877 rs1057519285 GRCh37: 19:36228163-36228163
GRCh38: 19:35737262-35737262
33 KMT2B NM_014727.3(KMT2B):c.3953G>T (p.Trp1318Leu) SNV Uncertain significance 930711 GRCh37: 19:36217204-36217204
GRCh38: 19:35726303-35726303
34 KMT2B NM_014727.3(KMT2B):c.3429+9G>A SNV Uncertain significance 932009 GRCh37: 19:36215641-36215641
GRCh38: 19:35724740-35724740
35 KMT2B NM_014727.3(KMT2B):c.4154C>T (p.Ser1385Leu) SNV Uncertain significance 982755 GRCh37: 19:36218375-36218375
GRCh38: 19:35727474-35727474
36 KMT2B NM_014727.2(KMT2B):c.1337C>T (p.Pro446Leu) SNV Uncertain significance 548572 rs769921695 GRCh37: 19:36211586-36211586
GRCh38: 19:35720684-35720684
37 KMT2B NM_014727.2(KMT2B):c.4986C>A (p.Phe1662Leu) SNV Uncertain significance 549479 rs372432644 GRCh37: 19:36220936-36220936
GRCh38: 19:35730035-35730035
38 KMT2B NM_014727.2(KMT2B):c.5284C>T (p.Arg1762Cys) SNV Uncertain significance 549481 rs1489232377 GRCh37: 19:36221615-36221615
GRCh38: 19:35730714-35730714
39 KMT2B NM_014727.2(KMT2B):c.8021T>C (p.Ile2674Thr) SNV Uncertain significance 549485 rs1555735051 GRCh37: 19:36229331-36229331
GRCh38: 19:35738430-35738430
40 KMT2B NM_014727.2(KMT2B):c.5114G>A (p.Arg1705Gln) SNV Uncertain significance 549489 rs1555731980 GRCh37: 19:36221280-36221280
GRCh38: 19:35730379-35730379
41 KMT2B NM_014727.2(KMT2B):c.4955G>A (p.Gly1652Asp) SNV Uncertain significance 549493 rs1555731832 GRCh37: 19:36220905-36220905
GRCh38: 19:35730004-35730004
42 KMT2B NM_014727.2(KMT2B):c.5342T>C (p.Leu1781Pro) SNV Uncertain significance 549496 rs1555732094 GRCh37: 19:36221673-36221673
GRCh38: 19:35730772-35730772
43 KMT2B NM_014727.3(KMT2B):c.648_649insA (p.Arg217fs) Insertion not provided 817932 rs1599668553 GRCh37: 19:36210897-36210898
GRCh38: 19:35719995-35719996

Expression for Dystonia 28, Childhood-Onset

Search GEO for disease gene expression data for Dystonia 28, Childhood-Onset.

Pathways for Dystonia 28, Childhood-Onset

GO Terms for Dystonia 28, Childhood-Onset

Sources for Dystonia 28, Childhood-Onset

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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