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Azorean disease(MJD)

MedGen UID:
9841
Concept ID:
C0024408
Disease or Syndrome
Synonyms: Azorean neurologic disease; Machado-Joseph Disease; MJD; Nigrospinodentatal degeneration; Spinocerebellar Ataxia Type 3; SPINOCEREBELLAR ATROPHY III; Spinocerebellar atrophy type 3; Spinopontine atrophy
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, 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.
Genetic anticipation
MedGen UID:
109454
Concept ID:
C0600498
Organism Attribute
Source: HPO
A mode of inheritance in which the severity of a disorder increases or the age of onset decreases as the disorder is passed from one generation to the next.
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: MJD - Machado-Joseph disease (91952008); Azorean disease (91952008); Portuguese-Azorean disease (91952008); Machado-Joseph disease (91952008); Machado Joseph disease (91952008); Spinocerebellar ataxia type 3 (91952008)
 
Gene (location): ATXN3 (14q32.12)
OMIM®: 109150
Orphanet: ORPHA98757

Definition

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is characterized by progressive cerebellar ataxia and variable findings including a dystonic-rigid syndrome, a parkinsonian syndrome, or a combined syndrome of dystonia and peripheral neuropathy. Neurologic findings tend to evolve as the disease progresses. [from GeneReviews]

Additional descriptions

From GeneReviews Overview
The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. In this GeneReview the hereditary ataxias are categorized by mode of inheritance and gene (or chromosome locus) in which pathogenic variants occur.  https://www.ncbi.nlm.nih.gov/books/NBK1138
From OMIM
Machado-Joseph disease, named for affected families of Azorean extraction, is an autosomal dominant progressive neurologic disorder characterized principally by ataxia, spasticity, and ocular movement abnormalities. Although independently described as a seemingly separate disorder, spinocerebellar ataxia-3 is now known to be the same as Machado-Joseph disease. Three classic clinical subtypes of MJD are recognized: type 1 with early onset and marked pyramidal and dystonic signs; type 2, or pure, with predominant cerebellar ataxia; and type 3 with later-onset and peripheral neuropathy (Franca et al., 2008).  http://www.omim.org/entry/109150
From GHR
Spinocerebellar ataxia type 3 (SCA3) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other early signs and symptoms of SCA3 include speech difficulties, uncontrolled muscle tensing (dystonia), muscle stiffness (spasticity), rigidity, tremors, bulging eyes, and double vision. People with this condition may experience sleep disorders such as restless leg syndrome or REM sleep behavior disorder. Restless leg syndrome is a condition characterized by numbness or tingling in the legs accompanied by an urge to move the legs to stop the sensations. REM sleep behavior disorder is a condition in which the muscles are active during the dream (REM) stage of sleep, so an affected person often acts out his or her dreams. These sleep disorders tend to leave affected individuals feeling tired during the day.Over time, individuals with SCA3 may develop loss of sensation and weakness in the limbs (peripheral neuropathy), muscle cramps, muscle twitches (fasciculations), and swallowing difficulties. Individuals with SCA3 may have problems with memory, planning, and problem solving.Signs and symptoms of the disorder typically begin in mid-adulthood but can appear anytime from childhood to late adulthood. People with SCA3 eventually require wheelchair assistance. They usually survive 10 to 20 years after symptoms first appear.  https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-3

Clinical features

Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
Drooping of the upper lid due to deficient development or paralysis of the levator palpebrae muscle.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
A symptom referring to difficulty in swallowing. It may be observed in patients with stroke, motor neuron disorders, cancer of the throat or mouth, head and neck injuries, Parkinson disease, and multiple sclerosis.
Diplopia
MedGen UID:
41600
Concept ID:
C0012569
Finding
A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include REFRACTIVE ERRORS; STRABISMUS; OCULOMOTOR NERVE DISEASES; TROCHLEAR NERVE DISEASES; ABDUCENS NERVE DISEASES; and diseases of the BRAIN STEM and OCCIPITAL LOBE.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.
Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
Gliosis is the focal proliferation of glial cells in the central nervous system.
Muscle cramps
MedGen UID:
7749
Concept ID:
C0026821
Sign or Symptom
A sustained and usually painful contraction of muscle fibers. This may occur as an isolated phenomenon or as a manifestation of an underlying disease process (e.g., UREMIA; HYPOTHYROIDISM; MOTOR NEURON DISEASE; etc.). (From Adams et al., Principles of Neurology, 6th ed, p1398)
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
An involuntary, persistent state of firm, tense muscles with marked resistance to passive movement.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
A reflex characterized by upward movement of the great toe and an outward movement of the rest of the toes, when the sole of the foot is stroked. It is a normal reflex up to the age of two. Its presence beyond that age indicates neurological damage.
Chronic pain
MedGen UID:
57452
Concept ID:
C0150055
Finding
A longstanding unpleasant sensation associated with real or perceived physical or mental trauma.
Abnormal electrooculogram
MedGen UID:
510708
Concept ID:
C0159104
Finding
The clinical electro-oculogram (EOG) is an electrophysiological test of function of the outer retina and retinal pigment epithelium (RPE) in which changes in electrical potential across the RPE are recorded during successive periods of dark and light adaptation.
Bradykinesia
MedGen UID:
115925
Concept ID:
C0233565
Sign or Symptom
Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement).
Progressive cerebellar ataxia
MedGen UID:
140727
Concept ID:
C0393525
Disease or Syndrome
Truncal ataxia
MedGen UID:
96535
Concept ID:
C0427190
Sign or Symptom
Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
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.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Atrophy (wasting) of the cerebellum.
Limb ataxia
MedGen UID:
196692
Concept ID:
C0750937
Finding
A kind of ataxia that affects movements of the extremities.
Decreased vibratory sensation
MedGen UID:
220959
Concept ID:
C1295585
Finding
A decrease in the ability to perceive vibration. Clinically, this is usually tested with a tuning fork which vibrates at 128 Hz and is applied to bony prominences such as the malleoli at the ankles or the metacarpal-phalangeal joints. There is a slow decay of vibration from the tuning fork. The degree of vibratory sense loss can be crudely estimated by counting the number of seconds that the examiner can perceive the vibration longer than the patient.
Supranuclear ophthalmoplegia
MedGen UID:
235616
Concept ID:
C1408507
Disease or Syndrome
A vertical gaze palsy with inability to direct the gaze of the eyes downwards.
Dysmetric saccades
MedGen UID:
322908
Concept ID:
C1836392
Finding
The controller signal for saccadic eye movements has two components: the pulse that moves the eye rapidly from one point to the next, and the step that holds the eye in the new position. When both the pulse and the step are not the correct size, a dysmetric refixation eye movement results.
Urinary bladder sphincter dysfunction
MedGen UID:
334804
Concept ID:
C1843663
Finding
Abnormal function of a sphincter of the urinary bladder.
Postural instability
MedGen UID:
334529
Concept ID:
C1843921
Finding
A tendency to fall or the inability to keep oneself from falling; imbalance. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, Use of the retropulsion test includes a rapid balance perturbation in the backward direction, and the number of balance correcting steps (or total absence thereof) is used to rate the degree of postural instability. Healthy subjects correct such perturbations with either one or two large steps, or without taking any steps, hinging rapidly at the hips while swinging the arms forward as a counterweight. In patients with balance impairment, balance correcting steps are often too small, forcing patients to take more than two steps. Taking three or more steps is generally considered to be abnormal, and taking more than five steps is regarded as being clearly abnormal. Markedly affected patients continue to step backward without ever regaining their balance and must be caught by the examiner (this would be called true retropulsion). Even more severely affected patients fail to correct entirely, and fall backward like a pushed toy soldier, without taking any corrective steps.
Dilated fourth ventricle
MedGen UID:
376050
Concept ID:
C1847117
Finding
An abnormal dilatation of the fourth cerebral ventricle.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Facial-lingual fasciculations
MedGen UID:
354727
Concept ID:
C1862359
Finding
Fasciculations affecting the tongue muscle and the musculature of the face.
Spinocerebellar tract degeneration
MedGen UID:
401075
Concept ID:
C1866751
Disease or Syndrome
Impaired horizontal smooth pursuit
MedGen UID:
355793
Concept ID:
C1866753
Finding
An abnormality of ocular smooth pursuit characterized by an impairment of the ability to track horizontally moving objects.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAzorean disease
Follow this link to review classifications for Azorean disease in Orphanet.

Professional guidelines

PubMed

van de Warrenburg BP, van Gaalen J, Boesch S, Burgunder JM, Dürr A, Giunti P, Klockgether T, Mariotti C, Pandolfo M, Riess O
Eur J Neurol 2014 Apr;21(4):552-62. Epub 2014 Jan 13 doi: 10.1111/ene.12341. PMID: 24418350
Gasser T, Finsterer J, Baets J, Van Broeckhoven C, Di Donato S, Fontaine B, De Jonghe P, Lossos A, Lynch T, Mariotti C, Schöls L, Spinazzola A, Szolnoki Z, Tabrizi SJ, Tallaksen CM, Zeviani M, Burgunder JM, Harbo HF; EFNS.
Eur J Neurol 2010 Feb;17(2):179-88. Epub 2009 Dec 28 doi: 10.1111/j.1468-1331.2009.02873.x. PMID: 20050888

Recent clinical studies

Etiology

Eto K, Sumi SM, Bird TD, McEvoy-Bush T, Boehnke M, Schellenberg G
Arch Neurol 1990 Sep;47(9):968-74. PMID: 2396938
Romanul FC, Fowler HL, Radvany J, Feldman RG, Feingold M
N Engl J Med 1977 Jun 30;296(26):1505-8. doi: 10.1056/NEJM197706302962606. PMID: 865531

Diagnosis

Goldberg-Stern H, D'jaldetti R, Melamed E, Gadoth N
Neurology 1994 Jul;44(7):1298-301. PMID: 8035934
Takahashi N, Odano I, Nishihara M, Yuasa T, Sakai K
Eur J Nucl Med 1994 Jul;21(7):615-20. PMID: 7957347
Bharucha NE, Bharucha EP, Bhabha SK
Arch Neurol 1986 Feb;43(2):142-4. PMID: 3947253
Fowler HL
Arch Neurol 1984 Sep;41(9):921-5. PMID: 6477227

Therapy

Takahashi N, Odano I, Nishihara M, Yuasa T, Sakai K
Eur J Nucl Med 1994 Jul;21(7):615-20. PMID: 7957347

Prognosis

Romanul FC, Fowler HL, Radvany J, Feldman RG, Feingold M
N Engl J Med 1977 Jun 30;296(26):1505-8. doi: 10.1056/NEJM197706302962606. PMID: 865531

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