Spinocerebellar ataxia

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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 a 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.[1]

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 TypeAverage Onset
(Range in Years)
Average Duration
(Range in Years)
What the patient experiencesCommon originProblems
with DNA
SCA1[2] (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[3] (ATXN2)3rd–4th decade
(<10 to >60)
10 years
(1–30)
Diminished velocity saccades
areflexia (absence of neurologic reflexes)
CubaCAG repeat, 12q
SCA3[4] (MJD) (ATXN3)4th decade
(10–70)
10 years
(1–20)
Also called Machado-Joseph disease (MJD)[5]
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)
Decadesareflexia (absence of neurologic reflexes) Chromosome 16q
SCA5 (SPTBN2)3rd–4th decade
(10–68)
>25 yearsPure cerebellar Chromosome 11
SCA6[6] (CACNA1A)5th–6th decade
(19–71)
>25 yearsDownbeating nystagmus, positional vertigo
Symptoms can appear for the first time as late as 65 years old.
 CAG repeat, 19p
Calcium channel gene
SCA7[7] (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[8] (IOSCA)39 yrs
(18–65)
Normal lifespanHorizontal nystagmus (a rapid, involuntary, oscillatory motion of the eyeball), instability, lack of coordination CTG repeat,[9] 13q
SCA10[10] (ATXN10)36 years9 yearsataxia, seizuresMexicoChromosome 22q linked
pentanucleotide repeat
SCA1130 yrs
(15–70)
Normal lifespanMild, remain ambulatory (able to walk about on one's own) 15q
SCA12[11] (PPP2R2B)33 yrs
(8–55)
 Head and hand tremor,
akinesia (loss of normal motor function, resulting in impaired muscle movement)
 CAG repeat, 5q
SCA13Childhood or adulthood depending on mutationDepending on KCNC3 (a kind of gene)Mental retardation 19q
SCA14[12] (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
SCA1639 yrs
(20–66)
1–40 yearsHead and hand tremor 8q
SCA17 (TBP) CAG repeat, 6q (TATA-binding protein)
SCA19, SCA22  Mild cerebellar syndrome, dysarthria  
SCA251.5–39 yrsUnknownataxia with sensory neuropathy, vomiting and gastrointestinal pain. 2p
SCA27[13]15–20 yrsUnknownataxia 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.[14] 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.

Treatment[edit]

There is no currently 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.[15] 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 [16] 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.[17] 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.[18] Speech language pathologists may use augmentative and alternative communication devices to help patients with impaired speech.

References[edit]

  1. ^ www.ataxia.org
  2. ^ sca1 at NIH/UW GeneTests
  3. ^ sca2 at NIH/UW GeneTests
  4. ^ sca3 at NIH/UW GeneTests
  5. ^ machado_joseph at NINDS
  6. ^ sca6 at NIH/UW GeneTests
  7. ^ sca7 at NIH/UW GeneTests
  8. ^ sca8 at NIH/UW GeneTests
  9. ^ 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. 
  10. ^ sca10 at NIH/UW GeneTests
  11. ^ sca12 at NIH/UW GeneTests
  12. ^ sca14 at NIH/UW GeneTests
  13. ^ Online 'Mendelian Inheritance in Man' (OMIM) 609307
  14. ^ "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.
  15. ^ Marsden, J; Harris C. (2011). "Cerebellar ataxia: pathophysiology and rehabilitation". Clin. Rehabil 25 (3): 195–216. doi:10.1177/0269215510382495. PMID 21321055. 
  16. ^ "SCA2 information sheet from www.ataxia.org". 
  17. ^ 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. 
  18. ^ 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]

NameOMIMRareDiseasesOther
Anemia, sideroblastic spinocerebellar ataxia; Pagon Bird Detter syndrome301310Disease ID 668 at NIH's Office of Rare Diseases
Friedreich's ataxia; Spinocerebellar ataxia, Friedreich229300Disease ID 6468 at NIH's Office of Rare Diseases
Infantile onset Spinocerebellar ataxia605361Disease ID 4062 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 1164400Disease ID 4071 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 2183090Disease ID 4072 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 3; Machado Joseph disease109150Disease ID 6801 at NIH's Office of Rare Diseasesmachado_joseph/detail_machado_joseph.htm at NINDS
Spinocerebellar ataxia 4600223Disease ID 9970 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 5600224Disease ID 4953 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 7164500Disease ID 4955 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 8603680Disease ID 4956 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 13605259Disease ID 9611 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 18607458Disease ID 9976 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 19607346Disease ID 9969 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 20608687Disease ID 9997 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 21607454Disease ID 9999 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 23610245Disease ID 9950 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 25608703Disease ID 9996 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 26609306Disease ID 9995 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 28610246Disease ID 9951 at NIH's Office of Rare Diseases
Spinocerebellar ataxia 30117360Disease ID 9975 at NIH's Office of Rare Diseases
Spinocerebellar ataxia amyotrophy deafness271245Disease ID 4957 at NIH's Office of Rare Diseases
Spinocerebellar ataxia, autosomal recessive 1606002Disease ID 4949 at NIH's Office of Rare Diseases
Spinocerebellar ataxia, autosomal recessive 3271250Disease ID 9971 at NIH's Office of Rare Diseases
Spinocerebellar ataxia, autosomal recessive 4607317Disease ID 4952 at NIH's Office of Rare Diseases
Spinocerebellar ataxia, autosomal recessive 5606937Disease ID 9977 at NIH's Office of Rare Diseases
Spinocerebellar ataxia, autosomal recessive 6608029Disease ID 4954 at NIH's Office of Rare Diseases
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy607250Disease ID 10000 at NIH's Office of Rare Diseases
Spinocerebellar ataxia, X-linked, 2302600Disease ID 9978 at NIH's Office of Rare Diseases
Spinocerebellar ataxia, X-linked, 3301790Disease ID 9981 at NIH's Office of Rare Diseases
Spinocerebellar ataxia, X-linked, 4301840Disease ID 9980 at NIH's Office of Rare Diseases