U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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
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)
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): ATXN3 (14q32.12)
 
Monarch Initiative: MONDO:0007182
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 pyramidal signs, a dystonic-rigid extrapyramidal syndrome, significant peripheral amyotrophy and generalized areflexia, progressive external ophthalmoplegia, action-induced facial and lingual fasciculations, and bulging eyes. Neurologic findings tend to evolve as the disorder progresses. [from GeneReviews]

Additional descriptions

From OMIM
Machado-Joseph disease (MJD), 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 (SCA3) 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 MedlinePlus Genetics
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://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-3

Clinical features

From HPO
Chronic pain
MedGen UID:
57452
Concept ID:
C0150055
Finding
Persistent pain, usually defined as pain that has lasted longer than 3 to 6 months.
Urinary bladder sphincter dysfunction
MedGen UID:
334804
Concept ID:
C1843663
Finding
Abnormal function of a sphincter of the urinary bladder.
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.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
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.
Abnormal autonomic nervous system physiology
MedGen UID:
8511
Concept ID:
C0013363
Disease or Syndrome
A functional abnormality of the autonomic nervous system.
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.
Fasciculations
MedGen UID:
5124
Concept ID:
C0015644
Sign or Symptom
Fasciculations are observed as small, local, involuntary muscle contractions (twitching) visible under the skin. Fasciculations result from increased irritability of an axon (which in turn is often a manifestation of disease of a motor neuron). This leads to sporadic discharges of all the muscle fibers controlled by the axon in isolation from other motor units.
Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
Gliosis is the focal proliferation of glial cells in the central nervous system.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
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.
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).
Abnormality of extrapyramidal motor function
MedGen UID:
115941
Concept ID:
C0234133
Sign or Symptom
A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless).
Parkinsonian disorder
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
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.
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.
Limb ataxia
MedGen UID:
196692
Concept ID:
C0750937
Finding
A kind of ataxia that affects movements of the extremities.
Impaired 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.
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.
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
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Muscle spasm
MedGen UID:
52431
Concept ID:
C0037763
Sign or Symptom
Sudden and involuntary contractions of one or more muscles.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Diplopia
MedGen UID:
41600
Concept ID:
C0012569
Disease or Syndrome
Diplopia is a condition in which a single object is perceived as two images, it is also known as double vision.
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.
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.
External ophthalmoplegia
MedGen UID:
57662
Concept ID:
C0162292
Disease or Syndrome
Paralysis of the external ocular muscles.
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
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.
Gaze-evoked nystagmus
MedGen UID:
1808161
Concept ID:
C5574666
Disease or Syndrome
Nystagmus made apparent by looking to the right or to the left.

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

Garcia I, Valente D, Carolino N, Dinis H, Sousa R, Duarte SC, Silva LJG, Pereira AMPT, Pena A
Toxicon 2023 Mar 15;225:107051. Epub 2023 Feb 18 doi: 10.1016/j.toxicon.2023.107051. PMID: 36804606
Oliveira JBL, Martinez ARM, França MC Jr
Expert Opin Pharmacother 2022 Oct;23(15):1687-1694. Epub 2022 Oct 19 doi: 10.1080/14656566.2022.2135432. PMID: 36254604
Correia M, Branco CC, Bruffaerts N, Balagué A, Mota-Vieira L
Gene 2013 Dec 10;532(1):132-9. Epub 2013 Sep 13 doi: 10.1016/j.gene.2013.08.099. PMID: 24042129

Recent clinical studies

Etiology

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. doi: 10.1212/wnl.44.7.1298. PMID: 8035934
Takahashi N, Odano I, Nishihara M, Yuasa T, Sakai K
Eur J Nucl Med 1994 Jul;21(7):615-20. doi: 10.1007/BF00285583. PMID: 7957347
Bharucha NE, Bharucha EP, Bhabha SK
Arch Neurol 1986 Feb;43(2):142-4. doi: 10.1001/archneur.1986.00520020036014. PMID: 3947253
Fowler HL
Arch Neurol 1984 Sep;41(9):921-5. doi: 10.1001/archneur.1984.04050200027013. PMID: 6477227

Therapy

Takahashi N, Odano I, Nishihara M, Yuasa T, Sakai K
Eur J Nucl Med 1994 Jul;21(7):615-20. doi: 10.1007/BF00285583. 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

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...