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Early-onset generalized limb-onset dystonia(DYT1)

MedGen UID:
338823
Concept ID:
C1851945
Disease or Syndrome
Synonyms: Dystonia 1; Dystonia 1, modifier of; Dystonia 1, torsion, autosomal dominant; Dystonia musculorum deformans 1; Dystonia-1, torsion; DYT1 Early-Onset Primary Dystonia; Early onset torsion dystonia; Early-Onset Primary Dystonia (DYT1); Oppenheim's dystonia
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): TOR1A (9q34.11)
 
Monarch Initiative: MONDO:0007492
OMIM®: 128100
Orphanet: ORPHA256

Definition

DYT1 early-onset isolated dystonia typically presents in childhood or adolescence and only on occasion in adulthood. Dystonic muscle contractions causing posturing or irregular tremor of a leg or arm are the most common presenting findings. Dystonia is usually first apparent with specific actions such as writing or walking. Over time, the contractions frequently (but not invariably) become evident with less specific actions and spread to other body regions. No other neurologic abnormalities are present. Disease severity varies considerably even within the same family. Isolated writer's cramp may be the only sign. [from GeneReviews]

Additional descriptions

From OMIM
'Dystonia' describes a neurologic condition characterized by involuntary, sustained muscle contractions affecting one or more sites of the body; 'torsion' refers to the twisting nature of body movements observed in dystonia. Dystonia has been classified as primary (dystonia as the sole or major symptom) or secondary (a symptom of another disorder), and by age of onset, muscle groups affected, and mode of inheritance (Muller and Kupke, 1990; Nemeth, 2002).  http://www.omim.org/entry/128100
From MedlinePlus Genetics
Early-onset isolated dystonia is one of many forms of dystonia, which is a group of conditions characterized by involuntary tensing of the muscles (muscle contractions), twisting of specific body parts such as an arm or a leg, rhythmic shaking (tremors), and other uncontrolled movements. An isolated dystonia is one that occurs without other abnormal movements or other neurological symptoms, such as seizures, a loss of intellectual function, or developmental or intellectual delay. Early-onset isolated dystonia does not affect a person's intelligence.

The signs and symptoms of early-onset isolated dystonia tend to occur in mid-childhood or adolescence. Abnormal muscle spasms in an arm or a leg are usually the first sign. These unusual movements initially occur while a person is doing a specific action, such as writing or  walking. In some affected people, dystonia later spreads to other parts of the body and the movements may become persistent and present when at rest and not doing an activity. The abnormal movements persist throughout life, but they do not usually cause pain.

The signs and symptoms of early-onset isolated dystonia vary from person to person, even among affected members of the same family.  The mildest cases affect only a single part of the body, causing isolated problems such as abnormal posture and spasms of the hand while attempting to write (writer's cramp). Severe cases involve abnormal movements affecting many parts of the body.  https://medlineplus.gov/genetics/condition/early-onset-isolated-dystonia

Clinical features

From HPO
Absent Achilles reflex
MedGen UID:
108240
Concept ID:
C0558845
Finding
Absence of the Achilles reflex (also known as the ankle jerk reflex), which can normally be elicited by tapping the tendon is tapped while the foot is dorsiflexed.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Torsion dystonia
MedGen UID:
3941
Concept ID:
C0013423
Disease or Syndrome
Sustained involuntary muscle contractions that produce twisting and repetitive movements of the body.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Torticollis
MedGen UID:
11859
Concept ID:
C0040485
Sign or Symptom
Torticollis is a twisted neck as a result of shortening of sternocleidomastoid muscle. This short and fibrotic muscle pulls the head laterally and rotates the chin and face to the opposite end. Facial asymmetry may be a manifestation (summary by Engin et al., 1997).
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Writer cramp
MedGen UID:
57821
Concept ID:
C0154676
Disease or Syndrome
A focal dystonia of the fingers, hand, and/or forearm that appears when the affected person attempts to do a task that requires fine motor movements such as writing or playing a musical instrument.
Abnormal posturing
MedGen UID:
66660
Concept ID:
C0231471
Finding
Involuntary flexion or extension of the arms and legs.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Generalized dystonia
MedGen UID:
341342
Concept ID:
C1848954
Finding
A type of dystonia that affects all or most of the body.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Oromandibular dystonia
MedGen UID:
473560
Concept ID:
C2242577
Sign or Symptom
A kind of focal dystonia characterized by forceful contractions of the face, jaw, and/or tongue causing difficulty in opening and closing the mouth and often affecting chewing and speech.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Hyperlordosis
MedGen UID:
9805
Concept ID:
C0024003
Finding
Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Multiple joint contractures
MedGen UID:
57633
Concept ID:
C0158118
Acquired Abnormality
Facial palsy
MedGen UID:
87660
Concept ID:
C0376175
Disease or Syndrome
Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Blepharospasm
MedGen UID:
599
Concept ID:
C0005747
Disease or Syndrome
A focal dystonia that affects the muscles of the eyelids and brow, associated with involuntary recurrent spasm of both eyelids.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVEarly-onset generalized limb-onset dystonia

Professional guidelines

PubMed

Albanese A, Asmus F, Bhatia KP, Elia AE, Elibol B, Filippini G, Gasser T, Krauss JK, Nardocci N, Newton A, Valls-Solé J
Eur J Neurol 2011 Jan;18(1):5-18. doi: 10.1111/j.1468-1331.2010.03042.x. PMID: 20482602

Recent clinical studies

Etiology

Elia AE, Filippini G, Bentivoglio AR, Fasano A, Ialongo T, Albanese A
Eur J Neurol 2006 Oct;13(10):1083-8. doi: 10.1111/j.1468-1331.2006.01387.x. PMID: 16987160
Bentivoglio AR, Loi M, Valente EM, Ialongo T, Tonali P, Albanese A
Mov Disord 2002 Sep;17(5):1058-63. doi: 10.1002/mds.10236. PMID: 12360559

Diagnosis

Albanese A, Asmus F, Bhatia KP, Elia AE, Elibol B, Filippini G, Gasser T, Krauss JK, Nardocci N, Newton A, Valls-Solé J
Eur J Neurol 2011 Jan;18(1):5-18. doi: 10.1111/j.1468-1331.2010.03042.x. PMID: 20482602
Elia AE, Filippini G, Bentivoglio AR, Fasano A, Ialongo T, Albanese A
Eur J Neurol 2006 Oct;13(10):1083-8. doi: 10.1111/j.1468-1331.2006.01387.x. PMID: 16987160
Fasano A, Nardocci N, Elia AE, Zorzi G, Bentivoglio AR, Albanese A
Mov Disord 2006 Sep;21(9):1411-8. doi: 10.1002/mds.21000. PMID: 16773641
Bentivoglio AR, Loi M, Valente EM, Ialongo T, Tonali P, Albanese A
Mov Disord 2002 Sep;17(5):1058-63. doi: 10.1002/mds.10236. PMID: 12360559

Therapy

Albanese A, Asmus F, Bhatia KP, Elia AE, Elibol B, Filippini G, Gasser T, Krauss JK, Nardocci N, Newton A, Valls-Solé J
Eur J Neurol 2011 Jan;18(1):5-18. doi: 10.1111/j.1468-1331.2010.03042.x. PMID: 20482602

Prognosis

Zech M, Boesch S, Maier EM, Borggraefe I, Vill K, Laccone F, Pilshofer V, Ceballos-Baumann A, Alhaddad B, Berutti R, Poewe W, Haack TB, Haslinger B, Strom TM, Winkelmann J
Am J Hum Genet 2016 Dec 1;99(6):1377-1387. Epub 2016 Nov 10 doi: 10.1016/j.ajhg.2016.10.010. PMID: 27839873Free PMC Article
Elia AE, Filippini G, Bentivoglio AR, Fasano A, Ialongo T, Albanese A
Eur J Neurol 2006 Oct;13(10):1083-8. doi: 10.1111/j.1468-1331.2006.01387.x. PMID: 16987160
Fasano A, Nardocci N, Elia AE, Zorzi G, Bentivoglio AR, Albanese A
Mov Disord 2006 Sep;21(9):1411-8. doi: 10.1002/mds.21000. PMID: 16773641
Kamm C, Castelon-Konkiewitz E, Naumann M, Heinen F, Brack M, Nebe A, Ceballos-Baumann A, Gasser T
Mov Disord 1999 Jul;14(4):681-3. doi: 10.1002/1531-8257(199907)14:4<681::aid-mds1020>3.0.co;2-m. PMID: 10435508

Clinical prediction guides

Zech M, Boesch S, Maier EM, Borggraefe I, Vill K, Laccone F, Pilshofer V, Ceballos-Baumann A, Alhaddad B, Berutti R, Poewe W, Haack TB, Haslinger B, Strom TM, Winkelmann J
Am J Hum Genet 2016 Dec 1;99(6):1377-1387. Epub 2016 Nov 10 doi: 10.1016/j.ajhg.2016.10.010. PMID: 27839873Free PMC Article
Elia AE, Filippini G, Bentivoglio AR, Fasano A, Ialongo T, Albanese A
Eur J Neurol 2006 Oct;13(10):1083-8. doi: 10.1111/j.1468-1331.2006.01387.x. PMID: 16987160
Fasano A, Nardocci N, Elia AE, Zorzi G, Bentivoglio AR, Albanese A
Mov Disord 2006 Sep;21(9):1411-8. doi: 10.1002/mds.21000. PMID: 16773641

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