Spinocerebellar ataxia

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Spinocerebellar ataxia
Classification and external resources
Brain-cerebellum.png
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]

Classification[edit]

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[edit]

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[edit]

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.

Treatment[edit]

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[edit]

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[edit]

  1. ^ "spinocerebellar ataxia" at Dorland's Medical Dictionary
  2. ^ http://www.ninds.nih.gov/disorders/ataxia/ataxia.htm
  3. ^ www.ataxia.org
  4. ^ sca1 at NIH/UW GeneTests
  5. ^ sca2 at NIH/UW GeneTests
  6. ^ sca3 at NIH/UW GeneTests
  7. ^ machado_joseph at NINDS
  8. ^ sca6 at NIH/UW GeneTests
  9. ^ sca7 at NIH/UW GeneTests
  10. ^ sca8 at NIH/UW GeneTests
  11. ^ 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. 
  12. ^ sca10 at NIH/UW GeneTests
  13. ^ sca12 at NIH/UW GeneTests
  14. ^ sca14 at NIH/UW GeneTests
  15. ^ Online 'Mendelian Inheritance in Man' (OMIM) 609307
  16. ^ "Spinocerebellar ataxia". Genes and Disease [Internet]. Bethesda MD: National Center for Biotechnology Information. 1998–. NBK22234.  Check date values in: |date= (help) — Gives a concise description of SCA, along with a picture of shrunken degenerated cerebellum.
  17. ^ Marsden, J; Harris C. (2011). "Cerebellar ataxia: pathophysiology and rehabilitation". Clin. Rehabil 25 (3): 195–216. doi:10.1177/0269215510382495. PMID 21321055. 
  18. ^ "SCA2 information sheet from www.ataxia.org". 
  19. ^ 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. 
  20. ^ 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[edit]

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