Spinocerebellar ataxia

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Spinocerebellar ataxia
Classification and external resources
Cerebellum (in blue) of the human brain
ICD-10	G11.
ICD-9	334
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.

Contents 1 Symptoms 2 Treatment and prognosis 3 Inheritance 4 Notable cases 5 References 6 External links

[edit] Symptoms

Spinocerebellar ataxia (SCA) is one of 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, and different ataxias are known to affect different regions within the cerebellum. ^[2]

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. Generally, a person with ataxia retains full mental capacity but may progressively lose physical control.

[edit] Treatment and prognosis

There is no known cure for spinocerebellar ataxia, which is a progressive disease (it gets worse with time), although not all types cause equally severe disability.

Treatments are generally limited to softening symptoms, not the disease itself. The condition can be irreversible. A person with this disease will usually end up needing to use a wheelchair, and eventually they may need assistance to perform daily tasks.

The treatment of incoordination or ataxia, then mostly involves the use of adaptive devices to allow the ataxic individual to maintain as much independence as possible. Such devices may include a cane, crutches, walker, or wheelchair for those with impaired gait; devices to assist with writing, feeding, and self care if hand and arm coordination are impaired; and communication devices for those with impaired speech.

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 can be subject to variation. 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.

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). Subsequently, 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 which have been found (not all listed).

Many SCAs below fall under the category of polyglutamine diseases, which are caused when a disease-associated protein (ie. 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 which 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[3] (ATXN1)	4th decade (<10 to >60)	15 years (10-28)	Hypermetric saccades, slow saccades, upper motor neuron (note: saccades relates to eye movement)		CAG repeat, 6p (Ataxin 1)
SCA2[4] (ATXN2)	3rd - 4th decade (<10 to >60)	10 years (1-30)	Diminished velocity saccades areflexia (absence of neurologic reflexes)	Cuba	CAG repeat, 12q
SCA3[5] (MJD) (ATXN3)	4th decade (10-70)	10 years (1-20)	Also called Machado-Joseph disease (MJD)[6] 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[7] (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[8] (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[9] (IOSCA)	39 yrs (18-65)	Normal lifespan	Horizontal nystagmus (a rapid, involuntary, oscillatory motion of the eyeball)		CTG repeat, 13q
SCA10[10] (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[11] (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[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
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

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).

[edit] Inheritance

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 are now known for which specific genetic information is available. 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

[edit] Notable cases

Sufferers from the disease include:

• Aya Kitō (19 July 1962 - 23 May 1988), a Japanese girl who wrote a diary about her experience with the disease. Her diary, titled '1 Litre of Tears' was published shortly before her death and later adopted into a television drama of the 1 Litre no Namida and the film A Litre of Tears.

[edit] References

[edit] 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
• Ichi Rittoru no Namida (One Litre of Tears) - A Japanese drama based on the true story of a girl who suffered from Spinocerebellar ataxia.
• CureAtaxia.org - One Chicago family's fight against SCA Type 1 Ataxia

• OMIM: 183090 Spinocerebellar ataxia 1 at NIH's Office of Rare Diseases
• OMIM: 164400 Spinocerebellar ataxia 2 at NIH's Office of Rare Diseases
  • ataxia at NINDS
  • msa at NINDS
  • opca_doc at NINDS
  • MedlinePlus Encyclopedia Olivopontocerebellar atrophy

• OMIM: 607317 Spinocerebellar ataxia, autosomal recessive 4 at NIH's Office of Rare Diseases
• OMIM: 600224 Spinocerebellar ataxia 5 at NIH's Office of Rare Diseases
• OMIM: 605259 Spinocerebellar ataxia 13 at NIH's Office of Rare Diseases
• OMIM: 117360 Spinocerebellar ataxia 30 at NIH's Office of Rare Diseases
• OMIM: 608703 Spinocerebellar ataxia 25 at NIH's Office of Rare Diseases
• OMIM: 600223 Spinocerebellar ataxia 4 at NIH's Office of Rare Diseases
• OMIM: 606002 Spinocerebellar ataxia, autosomal recessive 1 at NIH's Office of Rare Diseases
• OMIM: 271250 Spinocerebellar ataxia, autosomal recessive 3 at NIH's Office of Rare Diseases
• OMIM: 609306 Spinocerebellar ataxia 26 at NIH's Office of Rare Diseases
• OMIM: 608029 Spinocerebellar ataxia, autosomal recessive 6 at NIH's Office of Rare Diseases
• OMIM: 607346 Spinocerebellar ataxia 19 at NIH's Office of Rare Diseases
• OMIM: 608687 Spinocerebellar ataxia 20 at NIH's Office of Rare Diseases
• OMIM: 302600 Spinocerebellar ataxia, X-linked, 2 at NIH's Office of Rare Diseases
• OMIM: 606937 Spinocerebellar ataxia, autosomal recessive 5 at NIH's Office of Rare Diseases
• OMIM: 301840 Spinocerebellar ataxia, X-linked, 4 at NIH's Office of Rare Diseases
• OMIM: 301790 Spinocerebellar ataxia, X-linked, 3 at NIH's Office of Rare Diseases
• OMIM: 109150 Spinocerebellar ataxia 3; Machado Joseph disease at NIH's Office of Rare Diseases
  • machado_joseph/detail_machado_joseph.htm at NINDS
• OMIM: 607458 Spinocerebellar ataxia 18 at NIH's Office of Rare Diseases
• Spinocerebellar ataxia 27 at NIH's Office of Rare Diseases
• OMIM: 164500 Spinocerebellar ataxia 7 at NIH's Office of Rare Diseases
• OMIM: 607454 Spinocerebellar ataxia 99 at NIH's Office of Rare Diseases
• OMIM: 610245 Spinocerebellar ataxia 23 at NIH's Office of Rare Diseases
• OMIM: 610246 Spinocerebellar ataxia 28 at NIH's Office of Rare Diseases
• OMIM: 603680 Spinocerebellar ataxia 8 at NIH's Office of Rare Diseases
• OMIM: 607250 Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy at NIH's Office of Rare Diseases
• OMIM: 605361 Infantile onset Spinocerebellar ataxia at NIH's Office of Rare Diseases
• OMIM: 271245 Spinocerebellar ataxia amyotrophy deafness at NIH's Office of Rare Diseases
• Spinocerebellar ataxia dysmorphism at NIH's Office of Rare Diseases
• OMIM: 301310 Anemia, sideroblastic spinocerebellar ataxia; Pagon Bird Detter syndrome at NIH's Office of Rare Diseases
• OMIM: 229300 Friedreich's ataxia; Spinocerebellar ataxia, Friedreich at NIH's Office of Rare Diseases

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v • d • e Non-Mendelian inheritance: anticipation Trinucleotide repeat disorders Polyglutamine (PolyQ) Dentatorubral-pallidoluysian atrophy · Huntington's disease  · Kennedy disease · Spinocerebellar ataxia 1, 2, 3, 6, 7, 17 (Machado-Joseph disease) Non-Polyglutamine Fragile X syndrome · Friedreich's ataxia · Myotonic dystrophy type 1 · Spinocerebellar ataxia 8, 12 Four nucleotides Myotonic dystrophy type 2