| Spinocerebellar ataxia |
| Classification and external resources |
|
Cerebellum (in blue) of the human brain
|
| ICD-10 |
G11.1 |
| ICD-9 |
334 |
| OMIM |
164400 |
| DiseasesDB |
12339 |
| MeSH |
D020754 |
Spinocerebellar ataxia (SCA) is a progressive, degenerative,[1] genetic disease with multiple types, each of which could be considered a disease in its own right. An estimated 150,000 people in the United States are diagnosed with Ataxia. SCA's are the largest group of this hereditary, progressive, degenerative and often fatal neurodegenerative disorder. There is no known effective treatment or cure. Ataxia can affect anyone of any age. It is caused by either a recessive or dominant gene. Many times people are not aware that they carry the ataxia gene until they have children who begin to show signs of having the disorder.[2]
Contents
- 1 Classification
- 2 Signs and symptoms
- 3 Cause
- 4 Treatment
- 5 Rehabilitation
- 6 References
- 7 External links
Classification
There have been up to 60 different types of SCA identified (most are found on autopsy) as there is no test that can tell if an individual has SCA or what type it is. Many are misdiagnosed or go years without knowing the exact type. In 2008 there was an ataxia genetic blood test developed to test for 12 of these many types. This test for the most common hereditary types of Ataxia, which include Friedreich's ataxia, SCA 1,3,8, and a few more. However, in the SCA group, with so many different types most go with a diagnosis of SCA unidentified or unknown. Usually the diagnosis comes after examination by a neurologist, which includes a physical exam, family history, MRI scanning of the brain and spine, and spinal tap.[3]
The following is a list of some, not all, types of Spinocerebellar ataxia. The first ataxia gene was identified in 1993 for a dominantly inherited type. It was called “Spinocerebellar ataxia type 1" (SCA1). Subsequent to this, as additional dominant genes were found they were called SCA2, SCA3, etc. Usually, the "type" number of "SCA" refers to the order in which the gene was found. At this time, there are at least 29 different gene mutations that have been found (not all listed).
Many SCAs below fall under the category of polyglutamine diseases, which are caused when a disease-associated protein (i.e., ataxin-1, ataxin-3, etc.) contains a glutamine repeat beyond a certain threshold. In most dominant polyglutamine diseases, the glutamine repeat threshold is approximately 35, except for SCA3, which is beyond 50. Polyglutamine diseases are also known as "CAG Triplet Repeat Disorders" because CAG is the codon that codes for the amino acid glutamine. Many prefer to refer to these also as polyQ diseases, since "Q" is the one-letter reference for glutamine.
| SCA Type |
Average Onset
(Range in Years) |
Average Duration
(Range in Years) |
What the patient experiences |
Common origin |
Problems
with DNA |
| SCA1[4] (ATXN1) |
4th decade
(<10 to >60) |
15 years
(10–35) |
Hypermetric saccades, slow saccades, upper motor neuron
(note: saccades relates to eye movement) |
|
CAG repeat, 6p (Ataxin 1) |
| SCA2[5] (ATXN2) |
3rd–4th decade
(<10 to >60) |
10 years
(1–30) |
Diminished velocity saccades
areflexia (absence of neurologic reflexes) |
Cuba |
CAG repeat, 12q |
| SCA3[6] (MJD) (ATXN3) |
4th decade
(10–70) |
10 years
(1–20) |
Also called Machado-Joseph disease (MJD)[7]
Gaze-evoked nystagmus (a rapid, involuntary, oscillatory motion of the eyeball)
upper motor neuron
slow saccades |
Azores
(Portugal) |
CAG repeat, 14q |
| SCA4 (PLEKHG4) |
4th–7th decade
(19–72) |
Decades |
areflexia (absence of neurologic reflexes) |
|
Chromosome 16q |
| SCA5 (SPTBN2) |
3rd–4th decade
(10–68) |
>25 years |
Pure cerebellar |
|
Chromosome 11 |
| SCA6[8] (CACNA1A) |
5th–6th decade
(19–71) |
>25 years |
Downbeating nystagmus, positional vertigo
Symptoms can appear for the first time as late as 65 years old. |
|
CAG repeat, 19p
Calcium channel gene |
| SCA7[9] (ATXN7) |
3rd–4th decade
(0.5–60) |
20 years
(1–45; early onset correlates with shorter duration) |
Macular degeneration, upper motor neuron, slow saccades |
|
CAG repeat, 3p (Ataxin 7) |
| SCA8[10] (IOSCA) |
39 yrs
(18–65) |
Normal lifespan |
Horizontal nystagmus (a rapid, involuntary, oscillatory motion of the eyeball), instability, lack of coordination |
|
CTG repeat,[11] 13q |
| SCA10[12] (ATXN10) |
36 years |
9 years |
ataxia, seizures |
Mexico |
Chromosome 22q linked
pentanucleotide repeat |
| SCA11 |
30 yrs
(15–70) |
Normal lifespan |
Mild, remain ambulatory (able to walk about on one's own) |
|
15q |
| SCA12[13] (PPP2R2B) |
33 yrs
(8–55) |
|
Head and hand tremor,
akinesia (loss of normal motor function, resulting in impaired muscle movement) |
|
CAG repeat, 5q |
| SCA13 |
Childhood or adulthood depending on mutation |
Depending on KCNC3 (a kind of gene) |
Mental retardation |
|
19q |
| SCA14[14] (PRKCG) |
28 yrs
(12–42) |
Decades
(1–30) |
Myoclonus (a sudden twitching of muscles or parts of muscles, without any rhythm or pattern, occurring in various brain disorders) |
|
19q |
| SCA16 |
39 yrs
(20–66) |
1–40 years |
Head and hand tremor |
|
8q |
| SCA17 (TBP) |
|
CAG repeat, 6q (TATA-binding protein) |
| SCA19, SCA22 |
|
|
Mild cerebellar syndrome, dysarthria |
|
|
| SCA25 |
1.5–39 yrs |
Unknown |
ataxia with sensory neuropathy, vomiting and gastrointestinal pain. |
|
2p |
| SCA27[15] |
15–20 yrs |
Unknown |
ataxia with low cognition, dyskinesias and tremor. |
|
FGF14 13q34 |
Others include SCA18, SCA20, SCA21, SCA23, SCA26, SCA28, and SCA29.
Four X-linked types have been described (302500, 302600, 301790, 301840), but only the first of these has so far been tied to a gene (SCAX1).
Signs and symptoms
Spinocerebellar ataxia (SCA) is one of a group of genetic disorders characterized by slowly progressive incoordination of gait and is often associated with poor coordination of hands, speech, and eye movements. This frequent hand movements cause intentional tremor in these patients. Frequently, atrophy of the cerebellum occurs, and different ataxias are known to affect different regions within the cerebellum.[16] As with other forms of ataxia, SCA results in unsteady and clumsy motion of the body due to a failure of the fine coordination of muscle movements, along with other symptoms.
The symptoms of an ataxia vary with the specific type and with the individual patient. In general, a person with ataxia retains full mental capacity but may progressively lose physical control.
Cause
The hereditary ataxias are categorized by mode of inheritance and causative gene or chromosomal locus. The hereditary ataxias can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner.
- Many types of autosomal dominant cerebellar ataxias for which specific genetic information is available are now known. Synonyms for autosomal-dominant cerebellar ataxias (ADCA) used prior to the current understanding of the molecular genetics were Marie's ataxia, inherited olivopontocerebellar atrophy, cerebello-olivary atrophy, or the more generic term "spinocerebellar degeneration." (Spinocerebellar degeneration is a rare inherited neurological disorder of the central nervous system characterized by the slow degeneration of certain areas of the brain. There are three forms of spinocerebellar degeneration: Types 1, 2, 3. Symptoms begin during adulthood.)
- There are five typical autosomal-recessive disorders in which ataxia is a prominent feature: Friedreich ataxia, ataxia-telangiectasia, ataxia with vitamin E deficiency, ataxia with oculomotor apraxia (AOA), spastic ataxia. Disorder subdivisions: Friedreich's ataxia, Spinocerebellar ataxia, Ataxia telangiectasia, Vasomotor ataxia, Vestibulocerebellar, Ataxiadynamia, Ataxiophemia, Olivopontocerebellar atrophy, and Charcot-Marie-Tooth disease.
- There have been reported cases where a polyglutamine expansion may lengthen when passed down, which often can result in an earlier age-of-onset and a more severe disease phenotype for individuals who inherit the disease allele. This falls under the category of genetic anticipation.
-
There are numerous types of autosomal-dominant cerebellar ataxias
-
There are five typical autosomal recessive disorders in which ataxia is a prominent feature
Treatment
There is no known cure for spinocerebellar ataxia, which is considered to be a progressive and irreversible disease, although not all types cause equally severe disability. In general, treatments are directed towards alleviating symptoms, not the disease itself. Many patients with hereditary or idiopathic forms of ataxia have other symptoms in addition to ataxia. Medications or other therapies might be appropriate for some of these symptoms, which could include tremor, stiffness, depression, spasticity, and sleep disorders, among others. Both onset of initial symptoms and duration of disease are variable. If the disease is caused by a polyglutamine trinucleotide repeat CAG expansion, a longer expansion may lead to an earlier onset and a more radical progression of clinical symptoms. Typically, a person afflicted with this disease will eventually be unable to perform daily tasks (ADLs). However, rehabilitation therapists can help patients to maximize their ability of self-care and delay deterioration to certain extent. Stem cell research has been sought for a future treatment.
Rehabilitation
Physical therapists can assist patients in maintaining their level of independence through therapeutic exercise programs. In general, physical therapy emphasizes postural balance and gait training for ataxia patients.[17] General conditioning such as range-of-motion exercises and muscle strengthening would also be included in therapeutic exercise programs. Research showed that spinocerebellar ataxia 2 (SCA2) patients [18] with a mild stage of the disease gained significant improvement in static balance and neurological indices after six months of a physical therapy exercise training program.[19] Occupational therapists may assist patients with incoordination or ataxia issues through the use of adaptive devices. Such devices may include a cane, crutches, walker, or wheelchair for those with impaired gait. Other devices are available to assist with writing, feeding, and self care if hand and arm coordination are impaired. A randomized clinical trial revealed that an intensive rehabilitation program with physical and occupational therapies for patients with degenerative cerebellar diseases can significantly improve functional gains in ataxia, gait, and activities of daily living. Some level of improvement was shown to be maintained 24 weeks post-treatment.[20] Speech language pathologists may use augmentative and alternative communication devices to help patients with impaired speech.
References
- ^ "spinocerebellar ataxia" at Dorland's Medical Dictionary
- ^ http://www.ninds.nih.gov/disorders/ataxia/ataxia.htm
- ^ www.ataxia.org
- ^ sca1 at NIH/UW GeneTests
- ^ sca2 at NIH/UW GeneTests
- ^ sca3 at NIH/UW GeneTests
- ^ machado_joseph at NINDS
- ^ sca6 at NIH/UW GeneTests
- ^ sca7 at NIH/UW GeneTests
- ^ sca8 at NIH/UW GeneTests
- ^ Mosemiller AK, Dalton JC, Day JW, Ranum LP (2003). "Molecular genetics of spinocerebellar ataxia type 8 (SCA8)". Cytogenet. Genome Res. 100 (1–4): 175–83. doi:10.1159/000072852. PMID 14526178.
- ^ sca10 at NIH/UW GeneTests
- ^ sca12 at NIH/UW GeneTests
- ^ sca14 at NIH/UW GeneTests
- ^ Online 'Mendelian Inheritance in Man' (OMIM) 609307
- ^ "Spinocerebellar ataxia". Genes and Disease [Internet]. Bethesda MD: National Center for Biotechnology Information. 1998–. NBK22234. — Gives a concise description of SCA, along with a picture of shrunken degenerated cerebellum.
- ^ Marsden, J; Harris C. (2011). "Cerebellar ataxia: pathophysiology and rehabilitation". Clin. Rehabil 25 (3): 195–216. doi:10.1177/0269215510382495. PMID 21321055.
- ^ "SCA2 information sheet from www.ataxia.org".
- ^ Trujillo-Martín, MM; Serrano-Aguilar P; Monton-Alvarez F; Carrillo-Fumero R. (2009). "Effectiveness and safety of treatments for degenerative ataxias: a systematic review". Mov Disord. 24 (8): 1111–24. doi:10.1002/mds.22564. PMID 19412936.
- ^ Miyai, I; Ito M; Hattori N; Mihara M; Hatakenaka M; Yagura H; Sobue G; Nishizawa M. (December 2011). "Cerebellar Ataxia Rehabilitation Trial in Degenerative Cerebellar Diseases". Neurorehabil Neural Repair. 26 (5): 515–522. doi:10.1177/1545968311425918. PMID 22140200.
External links
- http://www.ataxia.org - National Ataxia Foundation is dedicated to helping families with ataxia through research, education, and support.
- Cerebellar Degenerations at tchain.com
- http://leedsdna.info/tests/DRPLA.htm
- http://www.ataxiaforums.co.uk
- Bird, Thomas D (23 January 2014). Hereditary Ataxia Overview. PMID 20301317. NBK1138. In Pagon RA, Bird TD, Dolan CR, et al., ed. (1993–). GeneReviews™ [Internet]. Seattle WA: University of Washington, Seattle.
- Moreira, Maria-Ceu; Koenig, Michel (December 8, 2011). Ataxia with Oculomotor Apraxia Type 2. PMID 20301333. NBK1154. In GeneReviews
- Pulst, Stefan-M (1 March 2012). Spinocerebellar Ataxia Type 13. PMID 20301404. NBK1225. In GeneReviews
- Brussino, Alessandro; Brusco, Alfredo; Dürr, Alexandra (7 February 2013). Spinocerebellar Ataxia Type 28. PMID 21595125. NBK54582. In GeneReviews
- Online 'Mendelian Inheritance in Man' (OMIM) Spinocerebellar Ataxia, Autosomal Recessive 1; SCAR1 -606002
- Online 'Mendelian Inheritance in Man' (OMIM) Senataxin; SETX -608465
- ataxia at NINDS
- msa at NINDS
- opca_doc at NINDS
- MedlinePlus Encyclopedia Olivopontocerebellar atrophy
- Spinocerebellar ataxia 27 at NIH's Office of Rare Diseases
- Spinocerebellar ataxia dysmorphism at NIH's Office of Rare Diseases
| Name |
OMIM |
RareDiseases |
Other |
| Anemia, sideroblastic spinocerebellar ataxia; Pagon Bird Detter syndrome |
301310 |
Disease ID 668 at NIH's Office of Rare Diseases |
|
| Friedreich's ataxia; Spinocerebellar ataxia, Friedreich |
229300 |
Disease ID 6468 at NIH's Office of Rare Diseases |
|
| Infantile onset Spinocerebellar ataxia |
605361 |
Disease ID 4062 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 1 |
164400 |
Disease ID 4071 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 2 |
183090 |
Disease ID 4072 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 3; Machado Joseph disease |
109150 |
Disease ID 6801 at NIH's Office of Rare Diseases |
machado_joseph/detail_machado_joseph.htm at NINDS |
| Spinocerebellar ataxia 4 |
600223 |
Disease ID 9970 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 5 |
600224 |
Disease ID 4953 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 7 |
164500 |
Disease ID 4955 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 8 |
603680 |
Disease ID 4956 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 13 |
605259 |
Disease ID 9611 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 18 |
607458 |
Disease ID 9976 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 19 |
607346 |
Disease ID 9969 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 20 |
608687 |
Disease ID 9997 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 21 |
607454 |
Disease ID 9999 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 23 |
610245 |
Disease ID 9950 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 25 |
608703 |
Disease ID 9996 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 26 |
609306 |
Disease ID 9995 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 28 |
610246 |
Disease ID 9951 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia 30 |
117360 |
Disease ID 9975 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia amyotrophy deafness |
271245 |
Disease ID 4957 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia, autosomal recessive 1 |
606002 |
Disease ID 4949 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia, autosomal recessive 3 |
271250 |
Disease ID 9971 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia, autosomal recessive 4 |
607317 |
Disease ID 4952 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia, autosomal recessive 5 |
606937 |
Disease ID 9977 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia, autosomal recessive 6 |
608029 |
Disease ID 4954 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy |
607250 |
Disease ID 10000 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia, X-linked, 2 |
302600 |
Disease ID 9978 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia, X-linked, 3 |
301790 |
Disease ID 9981 at NIH's Office of Rare Diseases |
|
| Spinocerebellar ataxia, X-linked, 4 |
301840 |
Disease ID 9980 at NIH's Office of Rare Diseases |
|
|
Non-Mendelian inheritance: anticipation
|
|
| Trinucleotide |
|
Polyglutamine (PolyQ), CAG
|
- Dentatorubral-pallidoluysian atrophy
- Huntington's disease
- Kennedy disease
- Spinocerebellar ataxia 1, 2, 3, 6, 7, 17 (Machado-Joseph disease)
|
|
|
Non-polyglutamine
|
- CGG (Fragile X syndrome)
- GAA (Friedreich's ataxia)
- CTG (Myotonic dystrophy type 1)
- CTG (Spinocerebellar ataxia 8)
- CAG (Spinocerebellar ataxia 12)
|
|
|
| Tetranucleotide |
- CCTG (Myotonic dystrophy type 2)
|
|
| Pentanucleotide |
- ATTCT (Spinocerebellar ataxia 10)
|
|
|
Inherited disorders of trafficking / vesicular transport proteins
|
|
| Vesicle formation |
| Lysosome/Melanosome: |
- HPS1-HPS7
- Hermansky–Pudlak syndrome
- LYST
|
|
| COPII: |
- SEC23A
- Cranio–lenticulo–sutural dysplasia
|
|
|
|
|
| APC: |
- AP1S2
- X-linked intellectual disability
- AP3B1
- Hermansky–Pudlak syndrome 2
- AP4M1
|
|
|
| Rab |
|
|
| Cytoskeleton |
| Myosin: |
|
|
| Microtubule: |
- SPG4
- Hereditary spastic paraplegia 4
|
|
| Kinesin: |
- KIF5A
- Hereditary spastic paraplegia 10
|
|
| Spectrin: |
|
|
|
| Vesicle fusion |
| Synaptic vesicle: |
- SNAP29
- STX11
- Hemophagocytic lymphohistiocytosis 4
|
|
| Caveolae: |
- CAV1
- Congenital generalized lipodystrophy 3
- CAV3
- Limb-girdle muscular dystrophy 2B, Long QT syndrome 9
|
|
| Vacuolar protein sorting: |
|
|
- DYSF
- Distal muscular dystrophy
|
|
|
See also vesicular transport proteins
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
|
