DYT16
MCID: DYS059
MIFTS: 43

Dystonia 16 (DYT16)

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

Aliases & Classifications for Dystonia 16

MalaCards integrated aliases for Dystonia 16:

Name: Dystonia 16 56 12 25 58 73 29 13 6 15 71
Dyt16 56 52 25 58 73
Young-Onset Dystonia- 52 25
Dystonia-16 52 73
Dyt-Prkra 52 25
Early-Onset Dystonia Parkinsonism 58
Dystonia, Type 16 39

Characteristics:

Orphanet epidemiological data:

58
dystonia 16
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
some patients become wheelchair-bound
onset between 7 and 18 years
four unrelated families have been reported (last curated february 2015)


HPO:

31
dystonia 16:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Dystonia 16

Genetics Home Reference : 25 Dystonia 16 is one of many forms of dystonia, which is a group of conditions characterized by involuntary movements, twisting (torsion) and tensing of various muscles, and unusual positioning of affected body parts. Dystonia 16 can appear at any age from infancy through adulthood, although it most often begins in childhood. The signs and symptoms of dystonia 16 vary among people with the condition. In many affected individuals, the disorder first affects muscles in one or both arms or legs. Tensing (contraction) of the muscles often sets the affected limb in an abnormal position, which may be painful and can lead to difficulty performing tasks, such as walking. In others, muscles in the neck are affected first, causing the head to be pulled backward and positioned with the chin in the air (retrocollis). In dystonia 16, muscles of the jaw, lips, and tongue are also commonly affected (oromandibular dystonia), causing difficulty opening and closing the mouth and problems with swallowing and speech. Speech can also be affected by involuntary tensing of the muscles that control the vocal cords (laryngeal dystonia), resulting in a quiet, breathy voice or an inability to speak clearly. Dystonia 16 gradually gets worse, eventually involving muscles in most parts of the body. Some people with dystonia 16 develop a pattern of movement abnormalities known as parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, tremors, and an inability to hold the body upright and balanced (postural instability). In dystonia 16, parkinsonism is relatively mild if it develops at all. The signs and symptoms of dystonia 16 usually do not get better when treated with drugs that are typically used for movement disorders.

MalaCards based summary : Dystonia 16, also known as dyt16, is related to dystonia and slc39a14 deficiency, and has symptoms including involuntary movements, torticollis and bradykinesia. An important gene associated with Dystonia 16 is PRKRA (Protein Activator Of Interferon Induced Protein Kinase EIF2AK2), and among its related pathways/superpathways are Translational Control and Cellular Transformation by HTLV1. Affiliated tissues include tongue and brain, and related phenotypes are limb dystonia and abnormal pyramidal sign

Disease Ontology : 12 A multifocal dystonia that is characterized by early-onset progressive limb dystonia, laryngeal and oromandibular dystonia, and parkinsonism, and that has material basis in autosomal recessive inheritance of homozygous mutation in the protein activator of interferon induced protein kinase EIF2AK2 (PRKRA) gene on chromosome 2q31.

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 210571 Definition Dystonia 16 (DYT16) is a very rare and newly discovered movement disorder which is characterized by early-onset progressive limb dystonia, laryngeal and oromandibular dystonia, and parkinsonism. Epidemiology It has been described in 8 patients from three Brazilian families and one German family to date. Clinical description Disease presents in infancy to late childhood with one of two possible phenotypes : either generalized dystonia or dystonia-parkinsonism not responsive to L-Dopa. Dystonia usually starts in one limb, becomes generalized and mainly affects the trunk, neck and oromandibular muscles. Motor and speech developmental delays were also reported. The phenotypic spectrum of this disease is still being determined. Pharmacological therapy is ineffective. Etiology DYT16 is caused by mutations in the protein kinase, interferon -inducible double stranded RNA dependent activator (PRKRA ) gene , located on chromosome 2q31.2. Genetic counseling DYT16 is inherited in an autosomal recessive manner, and genetic counseling is possible and recommended. Visit the Orphanet disease page for more resources.

UniProtKB/Swiss-Prot : 73 Dystonia 16: An early-onset dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT16 patients have progressive, generalized dystonia with axial muscle involvement, oro-mandibular (sardonic smile) and laryngeal dystonia and, in some cases, parkinsonian features.

More information from OMIM: 612067 PS128100

Related Diseases for Dystonia 16

Graphical network of the top 20 diseases related to Dystonia 16:



Diseases related to Dystonia 16

Symptoms & Phenotypes for Dystonia 16

Human phenotypes related to Dystonia 16:

58 31 (show all 24)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 limb dystonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002451
2 abnormal pyramidal sign 58 31 frequent (33%) Frequent (79-30%) HP:0007256
3 dysphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002015
4 hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001347
5 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
6 dysphonia 58 31 frequent (33%) Frequent (79-30%) HP:0001618
7 torticollis 58 31 frequent (33%) Frequent (79-30%) HP:0000473
8 unsteady gait 58 31 frequent (33%) Frequent (79-30%) HP:0002317
9 parkinsonism 58 31 frequent (33%) Frequent (79-30%) HP:0001300
10 orofacial dyskinesia 58 31 frequent (33%) Frequent (79-30%) HP:0002310
11 bradykinesia 58 31 frequent (33%) Frequent (79-30%) HP:0002067
12 postural tremor 58 31 frequent (33%) Frequent (79-30%) HP:0002174
13 lower limb pain 58 31 frequent (33%) Frequent (79-30%) HP:0012514
14 motor delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001270
15 cognitive impairment 31 occasional (7.5%) HP:0100543
16 intellectual disability 58 31 very rare (1%) Very rare (<4-1%) HP:0001249
17 delayed speech and language development 31 HP:0000750
18 dyskinesia 31 HP:0100660
19 gait disturbance 31 HP:0001288
20 involuntary movements 31 HP:0004305
21 limb pain 31 HP:0009763
22 laryngeal dystonia 31 HP:0012049
23 morphological abnormality of the pyramidal tract 31 HP:0002062
24 retrocollis 31 HP:0002544

Symptoms via clinical synopsis from OMIM:

56
Abdomen Gastrointestinal:
dysphagia

Head And Neck Neck:
torticollis
retrocollis

Voice:
spasmodic dysphonia

Neurologic Central Nervous System:
hyperreflexia
dysarthria
involuntary movements
dystonia
parkinsonism
more
Head And Neck Face:
grimacing
oromandibular dyskinesia

Clinical features from OMIM:

612067

UMLS symptoms related to Dystonia 16:


involuntary movements, torticollis, bradykinesia, pain in lower limb, abnormal pyramidal signs, grimacing, static tremor

MGI Mouse Phenotypes related to Dystonia 16:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.35 ALX4 BMP5 EIF2S1 PJVK PRKRA
2 hearing/vestibular/ear MP:0005377 8.8 BMP5 PJVK PRKRA

Drugs & Therapeutics for Dystonia 16

Search Clinical Trials , NIH Clinical Center for Dystonia 16

Genetic Tests for Dystonia 16

Genetic tests related to Dystonia 16:

# Genetic test Affiliating Genes
1 Dystonia 16 29 PRKRA

Anatomical Context for Dystonia 16

MalaCards organs/tissues related to Dystonia 16:

40
Tongue, Brain

Publications for Dystonia 16

Articles related to Dystonia 16:

(show all 33)
# Title Authors PMID Year
1
DYT16 revisited: exome sequencing identifies PRKRA mutations in a European dystonia family. 56 6 61
25142429 2014
2
A heterozygous frameshift mutation in PRKRA (DYT16) associated with generalised dystonia in a German patient. 6 56 61
18420150 2008
3
DYT16, a novel young-onset dystonia-parkinsonism disorder: identification of a segregating mutation in the stress-response protein PRKRA. 61 56 6
18243799 2008
4
Hereditary Dystonia Overview 6
20301334 2003
5
A truncated PACT protein resulting from a frameshift mutation reported in movement disorder DYT16 triggers caspase activation and apoptosis. 61
31246344 2019
6
[A rare early-onset dystonia (DYT16) in a Portuguese girl]. 61
29897611 2018
7
The prevalence of PRKRA mutations in idiopathic dystonia. 61
29279192 2018
8
Functional Genomic Analyses of Mendelian and Sporadic Disease Identify Impaired eIF2α Signaling as a Generalizable Mechanism for Dystonia. 61
27939583 2016
9
Thiamine and dystonia 16. 61
27448549 2016
10
PRKRA Mutation Causing Early-Onset Generalized Dystonia-Parkinsonism (DYT16) in an Italian Family. 61
26990861 2016
11
Altered activation of protein kinase PKR and enhanced apoptosis in dystonia cells carrying a mutation in PKR activator protein PACT. 61
26231208 2015
12
Rare inborn errors of metabolism with movement disorders: a case study to evaluate the impact upon quality of life and adaptive functioning. 61
25425461 2014
13
dsRNA binding protein PACT/RAX in gene silencing, development and diseases. 61
25554729 2014
14
Novel DYT11 gene mutation in patients without dopaminergic deficit (SWEDD) screened for dystonia. 61
25150291 2014
15
Dystonia. 61
24092288 2013
16
Genetics of dystonia: what's known? What's new? What's next? 61
23893446 2013
17
DYT16: the original cases. 61
22842711 2012
18
[New medications for dystonia]. 61
23196520 2012
19
Whispering dysphonia in an Australian family (DYT4): a clinical and genetic reappraisal. 61
21956287 2011
20
Molecular pathways in dystonia. 61
21134457 2011
21
Rare causes of dystonia parkinsonism. 61
20694531 2010
22
Dystonia-plus syndromes. 61
20590807 2010
23
Genetics of primary torsion dystonia. 61
20425035 2010
24
Systematic mutation analysis of seven dystonia genes in complex regional pain syndrome with fixed dystonia. 61
20066431 2010
25
Early onset primary dystonia. 61
19157930 2009
26
[Genetics of dystonia]. 61
19685389 2009
27
The monogenic primary dystonias. 61
19578124 2009
28
Screening for dystonia genes DYT1, 11 and 16 in patients with writer's cramp. 61
19441135 2009
29
High-throughput mutational analysis of TOR1A in primary dystonia. 61
19284587 2009
30
Clinical and genetic characterization of a large Dutch family with primary focal dystonia. 61
18823044 2008
31
DYT16: a new twist to familial dystonia. 61
18243800 2008
32
A survey of Italian cases of dystonia treated by deep brain stimulation. 61
18176524 2007
33
Intracortical excitability in the hand motor representation in hand dystonia and blepharospasm. 61
12360552 2002

Variations for Dystonia 16

ClinVar genetic disease variations for Dystonia 16:

6 (show top 50) (show all 60) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PRKRA NM_003690.5(PRKRA):c.665C>T (p.Pro222Leu)SNV Pathogenic 6346 rs121434410 2:179300991-179300991 2:178436264-178436264
2 PRKRA NM_003690.5(PRKRA):c.267_268del (p.His89fs)deletion Pathogenic 6347 rs730880307 2:179312281-179312282 2:178447554-178447555
3 PRKRA NM_003690.5(PRKRA):c.784+6A>TSNV Conflicting interpretations of pathogenicity 425237 rs188208530 2:179300866-179300866 2:178436139-178436139
4 PRKRA NM_003690.5(PRKRA):c.256C>G (p.Leu86Val)SNV Uncertain significance 469611 rs1311237497 2:179312293-179312293 2:178447566-178447566
5 PRKRA NM_003690.5(PRKRA):c.785-2_785-1insATATTTGGATATinsertion Uncertain significance 225447 rs751875722 2:179296982-179296983 2:178432255-178432256
6 PRKRA NM_003690.5(PRKRA):c.*265A>CSNV Uncertain significance 332614 rs886055201 2:179296559-179296559 2:178431832-178431832
7 PRKRA NM_003690.5(PRKRA):c.*79G>ASNV Uncertain significance 894433 2:179296745-179296745 2:178432018-178432018
8 PRKRA NM_003690.5(PRKRA):c.*158A>GSNV Uncertain significance 332618 rs3997877 2:179296666-179296666 2:178431939-178431939
9 PRKRA NM_003690.5(PRKRA):c.*151A>TSNV Uncertain significance 332619 rs886055203 2:179296673-179296673 2:178431946-178431946
10 PRKRA NM_003690.5(PRKRA):c.851G>T (p.Cys284Phe)SNV Uncertain significance 537332 rs199725025 2:179296915-179296915 2:178432188-178432188
11 PRKRA NM_003690.5(PRKRA):c.611C>G (p.Thr204Arg)SNV Uncertain significance 537333 rs1351253817 2:179301045-179301045 2:178436318-178436318
12 PRKRA NM_003690.5(PRKRA):c.377A>G (p.Asn126Ser)SNV Uncertain significance 537334 rs1553597653 2:179309168-179309168 2:178444441-178444441
13 PRKRA NM_003690.5(PRKRA):c.131T>C (p.Met44Thr)SNV Uncertain significance 537330 rs1553599437 2:179315073-179315073 2:178450346-178450346
14 PRKRA NM_003690.5(PRKRA):c.766A>G (p.Ile256Val)SNV Uncertain significance 537331 rs769913085 2:179300890-179300890 2:178436163-178436163
15 PRKRA NC_000002.11:g.(?_179296804)_(179456251_?)dupduplication Uncertain significance 583796 2:179296804-179456251 2:178432077-178591524
16 PRKRA NM_003690.5(PRKRA):c.335C>G (p.Pro112Arg)SNV Uncertain significance 653965 2:179309210-179309210 2:178444483-178444483
17 PRKRA NM_003690.5(PRKRA):c.32C>G (p.Pro11Arg)SNV Uncertain significance 654323 2:179315726-179315726 2:178450999-178450999
18 PRKRA NM_003690.5(PRKRA):c.637T>C (p.Cys213Arg)SNV Uncertain significance 689778 2:179301019-179301019 2:178436292-178436292
19 PRKRA NM_003690.5(PRKRA):c.233C>A (p.Thr78Lys)SNV Uncertain significance 836776 2:179314971-179314971 2:178450244-178450244
20 PRKRA NM_003690.5(PRKRA):c.*655T>CSNV Uncertain significance 894031 2:179296169-179296169 2:178431442-178431442
21 PRKRA NM_003690.5(PRKRA):c.*576G>ASNV Uncertain significance 894032 2:179296248-179296248 2:178431521-178431521
22 PRKRA NM_003690.5(PRKRA):c.*553A>GSNV Uncertain significance 894033 2:179296271-179296271 2:178431544-178431544
23 PRKRA NM_003690.5(PRKRA):c.796G>A (p.Ala266Thr)SNV Uncertain significance 893004 2:179296970-179296970 2:178432243-178432243
24 PRKRA NM_003690.5(PRKRA):c.654G>A (p.Leu218=)SNV Uncertain significance 893005 2:179301002-179301002 2:178436275-178436275
25 PRKRA NM_003690.5(PRKRA):c.80T>C (p.Ile27Thr)SNV Uncertain significance 893226 2:179315124-179315124 2:178450397-178450397
26 PRKRA NM_003690.5(PRKRA):c.54T>C (p.Ser18=)SNV Uncertain significance 893227 2:179315704-179315704 2:178450977-178450977
27 PRKRA NM_003690.5(PRKRA):c.-14C>TSNV Uncertain significance 894076 2:179315771-179315771 2:178451044-178451044
28 PRKRA NM_003690.5(PRKRA):c.-64C>GSNV Uncertain significance 894077 2:179315821-179315821 2:178451094-178451094
29 PRKRA NM_003690.5(PRKRA):c.-124C>ASNV Uncertain significance 894078 2:179315881-179315881 2:178451154-178451154
30 PRKRA NM_003690.5(PRKRA):c.-125G>ASNV Uncertain significance 894468 2:179315882-179315882 2:178451155-178451155
31 PRKRA NM_003690.5(PRKRA):c.-141C>ASNV Uncertain significance 894469 2:179315898-179315898 2:178451171-178451171
32 PRKRA NM_003690.5(PRKRA):c.-104G>ASNV Uncertain significance 332639 rs545506202 2:179315861-179315861 2:178451134-178451134
33 PRKRA NM_003690.5(PRKRA):c.*313G>ASNV Uncertain significance 332613 rs3997879 2:179296511-179296511 2:178431784-178431784
34 PRKRA NM_003690.5(PRKRA):c.870C>T (p.Ser290=)SNV Uncertain significance 332621 rs537898766 2:179296896-179296896 2:178432169-178432169
35 PRKRA NM_003690.5(PRKRA):c.784+15T>CSNV Uncertain significance 332622 rs367606024 2:179300857-179300857 2:178436130-178436130
36 PRKRA NM_003690.5(PRKRA):c.-11C>TSNV Uncertain significance 332636 rs767401214 2:179315768-179315768 2:178451041-178451041
37 PRKRA NM_003690.5(PRKRA):c.-117C>TSNV Uncertain significance 332640 rs886055204 2:179315874-179315874 2:178451147-178451147
38 PRKRA NM_003690.5(PRKRA):c.-133C>GSNV Uncertain significance 332641 rs80197731 2:179315890-179315890 2:178451163-178451163
39 PRKRA NM_003690.5(PRKRA):c.*180C>TSNV Uncertain significance 332616 rs886055202 2:179296644-179296644 2:178431917-178431917
40 PRKRA NM_003690.5(PRKRA):c.-65C>GSNV Uncertain significance 332638 rs557426364 2:179315822-179315822 2:178451095-178451095
41 PRKRA NM_003690.5(PRKRA):c.65+10C>TSNV Likely benign 332632 rs535076601 2:179315683-179315683 2:178450956-178450956
42 PRKRA NM_003690.5(PRKRA):c.*31G>ASNV Likely benign 894434 2:179296793-179296793 2:178432066-178432066
43 PRKRA NM_003690.5(PRKRA):c.861C>T (p.Ser287=)SNV Likely benign 518334 rs116833881 2:179296905-179296905 2:178432178-178432178
44 PJVK , PRKRA NM_003690.5(PRKRA):c.32C>T (p.Pro11Leu)SNV Benign/Likely benign 332633 rs62176112 2:179315726-179315726 2:178450999-178450999
45 PJVK , PRKRA NM_003690.5(PRKRA):c.1A>C (p.Met1Leu)SNV Benign/Likely benign 332635 rs9406386 2:179315757-179315757 2:178451030-178451030
46 PJVK , PRKRA NM_003690.5(PRKRA):c.-24G>ASNV Benign/Likely benign 332637 rs62176113 2:179315781-179315781 2:178451054-178451054
47 PRKRA NM_003690.5(PRKRA):c.610-11_610-10delshort repeat Benign/Likely benign 332625 rs138320145 2:179301056-179301057 2:178436329-178436330
48 PRKRA NM_003690.5(PRKRA):c.173A>G (p.Asp58Gly)SNV Benign/Likely benign 332631 rs61999302 2:179315031-179315031 2:178450304-178450304
49 PJVK , PRKRA NM_003690.5(PRKRA):c.20_21GC[1] (p.Ala8fs)short repeat Benign/Likely benign 332634 rs141354030 2:179315735-179315736 2:178451008-178451009
50 PRKRA NM_003690.5(PRKRA):c.*198C>TSNV Benign 332615 rs3997878 2:179296626-179296626 2:178431899-178431899

UniProtKB/Swiss-Prot genetic disease variations for Dystonia 16:

73
# Symbol AA change Variation ID SNP ID
1 PRKRA p.Pro222Leu VAR_046213 rs121434410

Expression for Dystonia 16

Search GEO for disease gene expression data for Dystonia 16.

Pathways for Dystonia 16

Pathways related to Dystonia 16 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.24 PRKRA EIF2S1
2
Show member pathways
10.33 PRKRA EIF2S1

GO Terms for Dystonia 16

Biological processes related to Dystonia 16 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 skeletal system development GO:0001501 9.32 BMP5 ALX4
2 cellular response to oxidative stress GO:0034599 9.26 PRKRA EIF2S1
3 pattern specification process GO:0007389 9.16 BMP5 ALX4
4 skeletal system morphogenesis GO:0048705 8.96 PRKRA ALX4
5 ear development GO:0043583 8.62 PRKRA BMP5

Sources for Dystonia 16

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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