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Dyskinesia with orofacial involvement, autosomal dominant(DSKOD)

MedGen UID:
1790407
Concept ID:
C5551343
Disease or Syndrome
Synonyms: DSKOD; Dyskinesia, familial, with facial myokymia; Familial dyskinesia and facial myokymia
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): ADCY5 (3q21.1)
 
Monarch Initiative: MONDO:0800028
OMIM®: 606703
Orphanet: ORPHA324588

Disease characteristics

Excerpted from the GeneReview: ADCY5 Dyskinesia
ADCY5 dyskinesia is a hyperkinetic movement disorder (more prominent in the face and arms than the legs) characterized by infantile to late-adolescent onset of chorea, athetosis, dystonia, myoclonus, or a combination of these. To date, affected individuals have had overlapping (but not identical) manifestations with wide-ranging severity. The facial movements are typically periorbital and perioral. The dyskinesia is prone to episodic or paroxysmal exacerbation lasting minutes to hours, and may occur during sleep. Precipitating factors in some persons have included emotional stress, intercurrent illness, sneezing, or caffeine; in others, no precipitating factors have been identified. In some children, severe infantile axial hypotonia results in gross motor delays accompanied by chorea, sometimes with language delays. The overall tendency is for the abnormal movements to stabilize in early middle age, at which point they may improve in some individuals; less commonly, the abnormal movements are slowly progressive, increasing in severity and frequency. [from GeneReviews]
Authors:
Fuki M Hisama  |  Jennifer Friedman  |  Wendy H Raskind, et. al.   view full author information

Additional descriptions

From OMIM
Autosomal dominant dyskinesia with orofacial involvement (DSKOD) is a complex neurologic disorder characterized by onset of involuntary choreiform, myoclonic, and dystonic movements involving the neck, limb, and facial muscles in the first decade of life. The manifestations and severity are variable; the disorder can also include episodic weakness and spasticity, resulting in difficulty walking and talking. It is generally nonprogressive, especially in adulthood, and dementia is not observed, although some individuals may have difficulties in school or behavioral abnormalities, such as social isolation (summary by Chen et al., 2014; Carapito et al., 2015; Dean et al., 2019; Vijiaratnam et al., 2019). Vijiaratnam et al. (2019) provided a review of ADCY5-related dyskinesia, noting that the phenotypic features, manifestations, and severity are broad and variable. There are also variable molecular findings, including de novo mutations and mosaicism, the latter of which can influence expressivity.  http://www.omim.org/entry/606703
From MedlinePlus Genetics
ADCY5-related dyskinesia is a movement disorder; the term "dyskinesia" refers to abnormal involuntary movements. The abnormal movements that occur in ADCY5-related dyskinesia typically appear as sudden (paroxysmal) jerks, twitches, tremors, muscle tensing (dystonia), or writhing (choreiform) movements, and can affect the limbs, neck, and face.

The abnormal movements associated with ADCY5-related dyskinesia usually begin between infancy and late adolescence. They can occur continually during waking hours, and frequently also disturb sleep. The involuntary movements often occur when changing position, such as from sitting to standing, or when deliberately making other movements.

Severely affected infants may experience weak muscle tone (hypotonia) and delay in development of motor skills such as crawling and walking; later, these individuals may have difficulties with activities of daily living and may eventually require a wheelchair. In more mildly affected individuals, the condition has little impact on walking and other motor skills, although the abnormal movements can lead to clumsiness or difficulty with social acceptance in school or other situations.

In some people with ADCY5-related dyskinesia, the disorder is generally stable throughout their lifetime. In others, it slowly gets worse (progresses) in both frequency and severity before stabilizing or even improving in middle age. Anxiety, fatigue, and other stress can temporarily increase the severity of the signs and symptoms of ADCY5-related dyskinesia, while some affected individuals may experience remission periods of days or weeks without abnormal movements. Life expectancy is not usually affected by ADCY5-related dyskinesia, and most people with this condition have normal intelligence.  https://medlineplus.gov/genetics/condition/adcy5-related-dyskinesia

Clinical features

From HPO
Limb hypertonia
MedGen UID:
333083
Concept ID:
C1838391
Finding
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.\n\nIt usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Chorea
MedGen UID:
3420
Concept ID:
C0008489
Disease or Syndrome
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities.
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.
Dyskinesia
MedGen UID:
8514
Concept ID:
C0013384
Disease or Syndrome
A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Choreoathetosis
MedGen UID:
39313
Concept ID:
C0085583
Disease or Syndrome
Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Resting tremor
MedGen UID:
66697
Concept ID:
C0234379
Sign or Symptom
A resting tremor occurs when muscles are at rest and becomes less noticeable or disappears when the affected muscles are moved. Resting tremors are often slow and coarse.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Facial myokymia
MedGen UID:
78741
Concept ID:
C0270871
Disease or Syndrome
Facial myokymia is a fine fibrillary activity of one or more muscles innervated by the facial nerve (the seventh cranial nerve).
Involuntary movements
MedGen UID:
140884
Concept ID:
C0427086
Sign or Symptom
Involuntary contractions of muscle leading to involuntary movements of extremities, neck, trunk, or face.
Paroxysmal dyskinesia
MedGen UID:
156242
Concept ID:
C0752210
Disease or Syndrome
Episodic bouts of involuntary movements with dystonic, choreic, ballistic movements, or a combination thereof. There is no loss of consciousness during the attacks.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Delayed ability to sit
MedGen UID:
1368737
Concept ID:
C4476710
Finding
A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age.
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.
Neck muscle weakness
MedGen UID:
66808
Concept ID:
C0240479
Finding
Decreased strength of the neck musculature.
Idiopathic camptocormia
MedGen UID:
120496
Concept ID:
C0264162
Finding
An abnormal forward-flexed posture e.g. forward flexion of the spine, which is noticeable when standing or walking but disappears when lying down. It is becoming an increasingly recognized feature of Parkinson's disease and dystonic disorders.
Generalized muscle weakness
MedGen UID:
155433
Concept ID:
C0746674
Sign or Symptom
Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDyskinesia with orofacial involvement, autosomal dominant

Recent clinical studies

Diagnosis

Rangel YA, Espinosa E
Biomedica 2022 Sep 2;42(3):429-434. doi: 10.7705/biomedica.6296. PMID: 36122281Free PMC Article

Prognosis

Rangel YA, Espinosa E
Biomedica 2022 Sep 2;42(3):429-434. doi: 10.7705/biomedica.6296. PMID: 36122281Free PMC Article

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