DYT16
MCID: DYS059
MIFTS: 41

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 slc39a14 deficiency and dystonia 12, and has symptoms including involuntary movements, bradykinesia and torticollis. An important gene associated with Dystonia 16 is PRKRA (Protein Activator Of Interferon Induced Protein Kinase EIF2AK2). Affiliated tissues include tongue, brain and eye, and related phenotypes are limb dystonia and hyperreflexia

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 hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001347
3 abnormal pyramidal sign 58 31 frequent (33%) Frequent (79-30%) HP:0007256
4 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
5 dysphonia 58 31 frequent (33%) Frequent (79-30%) HP:0001618
6 dysphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002015
7 postural tremor 58 31 frequent (33%) Frequent (79-30%) HP:0002174
8 bradykinesia 58 31 frequent (33%) Frequent (79-30%) HP:0002067
9 torticollis 58 31 frequent (33%) Frequent (79-30%) HP:0000473
10 lower limb pain 58 31 frequent (33%) Frequent (79-30%) HP:0012514
11 parkinsonism 58 31 frequent (33%) Frequent (79-30%) HP:0001300
12 unsteady gait 58 31 frequent (33%) Frequent (79-30%) HP:0002317
13 orofacial dyskinesia 58 31 frequent (33%) Frequent (79-30%) HP:0002310
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 gait disturbance 31 HP:0001288
18 delayed speech and language development 31 HP:0000750
19 dyskinesia 31 HP:0100660
20 involuntary movements 31 HP:0004305
21 laryngeal dystonia 31 HP:0012049
22 limb pain 31 HP:0009763
23 morphological abnormality of the pyramidal tract 31 HP:0002062
24 retrocollis 31 HP:0002544

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
hyperreflexia
dysarthria
dystonia
involuntary movements
postural tremor
more
Head And Neck Neck:
torticollis
retrocollis

Voice:
spasmodic dysphonia

Abdomen Gastrointestinal:
dysphagia

Head And Neck Face:
grimacing
oromandibular dyskinesia

Clinical features from OMIM:

612067

UMLS symptoms related to Dystonia 16:


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

GenomeRNAi Phenotypes related to Dystonia 16 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased Aire reporter expression GR00304-A 8.62 ALX4 PRKRA

MGI Mouse Phenotypes related to Dystonia 16:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.33 ALX4 BMP5 PRKRA
2 hearing/vestibular/ear MP:0005377 9.13 BMP5 PJVK PRKRA
3 limbs/digits/tail MP:0005371 8.8 ALX4 BMP5 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, Eye

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. 61 56 6
25142429 2014
2
A heterozygous frameshift mutation in PRKRA (DYT16) associated with generalised dystonia in a German patient. 61 56 6
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 all 17) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# 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.256C>G (p.Leu86Val)SNV Uncertain significance 469611 rs1311237497 2:179312293-179312293 2:178447566-178447566
4 PRKRA NM_003690.5(PRKRA):c.785-2_785-1insATATTTGGATATinsertion Uncertain significance 225447 rs751875722 2:179296982-179296983 2:178432255-178432256
5 PRKRA NM_003690.5(PRKRA):c.851G>T (p.Cys284Phe)SNV Uncertain significance 537332 rs199725025 2:179296915-179296915 2:178432188-178432188
6 PRKRA NM_003690.5(PRKRA):c.611C>G (p.Thr204Arg)SNV Uncertain significance 537333 rs1351253817 2:179301045-179301045 2:178436318-178436318
7 PRKRA NM_003690.5(PRKRA):c.377A>G (p.Asn126Ser)SNV Uncertain significance 537334 rs1553597653 2:179309168-179309168 2:178444441-178444441
8 PRKRA NM_003690.5(PRKRA):c.131T>C (p.Met44Thr)SNV Uncertain significance 537330 rs1553599437 2:179315073-179315073 2:178450346-178450346
9 PRKRA NM_003690.5(PRKRA):c.766A>G (p.Ile256Val)SNV Uncertain significance 537331 rs769913085 2:179300890-179300890 2:178436163-178436163
10 PRKRA NC_000002.11:g.(?_179296804)_(179456251_?)dupduplication Uncertain significance 583796 2:179296804-179456251 2:178432077-178591524
11 PRKRA NM_003690.5(PRKRA):c.335C>G (p.Pro112Arg)SNV Uncertain significance 653965 2:179309210-179309210 2:178444483-178444483
12 PRKRA NM_003690.5(PRKRA):c.32C>G (p.Pro11Arg)SNV Uncertain significance 654323 2:179315726-179315726 2:178450999-178450999
13 PRKRA NM_003690.5(PRKRA):c.637T>C (p.Cys213Arg)SNV Uncertain significance 689778 2:179301019-179301019 2:178436292-178436292
14 PRKRA NM_003690.5(PRKRA):c.861C>T (p.Ser287=)SNV Likely benign 518334 rs116833881 2:179296905-179296905 2:178432178-178432178
15 PJVK , PRKRA NM_003690.5(PRKRA):c.1A>C (p.Met1Leu)SNV Benign/Likely benign 332635 rs9406386 2:179315757-179315757 2:178451030-178451030
16 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
17 PRKRA NM_001139517.1(PRKRA):c.27_28ins57 (p.?)insertion Benign 522281 2:179315143-179315144 2:178450416-178450417

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

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 regulation of apoptotic process GO:0042981 9.32 BMP5 ALX4
2 skeletal system development GO:0001501 9.26 BMP5 ALX4
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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