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Spinocerebellar Ataxia

A Group of Genetic Disorders Causing Clumsiness

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Updated November 14, 2012

Written or reviewed by a board-certified physician. See About.com's Medical Review Board.

When people discuss spinal cerebellar ataxia (SCA), they are actually referring to a group of neurodegenerative disorders that cause progressive clumsiness. There are more than 35 different types of spinal cerebellar ataxias, each caused by a different genetic mutation. Furthermore, new forms continue to be discovered.

Despite there being so many different variations, SCA is actually pretty rare. Even so, it is one of the most common causes of genetic ataxia. Even among people with no family history who develop ataxia for no other clear reason, a new SCA mutation can be found about 20 percent of the time.

What Causes SCA?

SCA is due to a genetic mutation. Many types are due to so-called expansion mutations, in which several nucleotides (usually cytosine, adenosine, and guanine) repeat more than is found in healthy people. In the common form involving three nucleotides repeating, this is called a trinucleotide repeat. The result of that repetition is that a mutated form of protein is expressed, leading to disease symptoms.

Spinocerebellar ataxia is usually inherited in an autosomal dominant fashion, meaning that if one of the parents has the disorder, there is about a 50 percent chance that a child will have the disease as well.

As the name spinocerebellar ataxia suggests, the disease afflicts the cerebellum and more. The brainstem can also waste away (atrophy), especially in SCA types 1, 2, and 7. The regions of the atrophy often control eye movements, leading to abnormal findings when a neurologist performs their physical exam.

What Is the Prognosis in Spinal Cerebellar Atrophy?

Spinocerebellar ataxias due to repeat expansion mutations usually become sick in middle age. In addition to ataxia, other neurological findings are often present depending on the variant of SCA. In general, the longer the repeat is, the younger the patient will be when the symptoms come on, and the more rapid the disease progression.

In general, SCA type 1 is more aggressive than types 2 or 3, and type 6 is the least aggressive SCA due to a trinucleotide repeat. We don’t have much information on other types of spinocerebellar ataxias, but most people will require a wheelchair 10 to 15 years after the symptoms come on. While most forms of SCA shorten the lifespan, this is not always the case.

How Is Spinocerebellar Atrophy Treated?

There is no cure for SCA. Medications such as zolpidem or varenicline have been suggested to help ataxia in SCA type 2 and 3 respectively.

SCA1

SCA1 causes about 3 to 16 percent of autosomal dominant cerebellar ataxias. In addition to ataxia, SCA1 is associated with difficulty speaking and swallowing. Increased reflexes are also common. Some patients also develop muscle wasting.

The mutation of SCA1 is a trinucleotide repeat in a region called ataxin 1. The mutated form of ataxin 1 clumps together in cells, and may change how nerve cells translate their own genetic codes. This is especially true in cells of the cerebellum.

SCA2

About 6 to 18 percent of people with spinocerebellar ataxia have SCA2. SCA 2 also causes coordination problems, but also causes slow eye movements. In severe cases, SCA 2 can cause developmental delay, seizures, and difficulty swallowing even in infancy.

SCA2 is caused by another trinucleotide repeat, this time encoding a protein called ataxin 2. Wheras SCA1 affects the nucleus of the cell and DNA, SCA2 seems to affect RNA and collects outside the nucleus.

SCA2 demonstrates how different people can suffer different symptoms even if they have the same mutation. An Italian family with SCA2 has suffered mental deterioration, and families from Tunesia have suffered chorea and dystonia.

SCA3

SCA3, better known as Machado-Joseph disease, is the most common autosomal dominant SCA, making up between 21 to 23 percent of SCA in the United States. In addition to ataxia, patients with Machado-Joseph have slow eye movements and difficulty swallowing. Cognitive impairments may also occur, as can dysautonomia. On the neurologists exam, patients with SCA3 may have a mixture of upper and lower motor neuron findings suggestive of amyotrophic lateral sclerosis.

SCA 4 and 5

These forms are less common, and are not due to trinucleotide repeats. SCA4 can have a peripheral neuropathy, but that’s true of most spinocerebellar ataxias. SCA5 has almost no other symptoms than ataxia. SCA5 tends to be mild and progress slowly. Interestingly, the original mutation seems to have descended from the paternal grandparents of Abraham Lincoln.

SCA6

SCA6 accounts for 15 to 17 percent of SCA. The mutation is in a gene also associated with episodic ataxia and some forms of migraine. In addition to ataxia, an abnormal eye movement known as nystagmus may appear on the neurological examination.

SCA7

SCA7 only comprises 2 to 5 percent of autosomal dominant spinocerbellar ataxias. The symptoms depend on the age of the patient and the size of the repeat. Vision loss is sometimes associated with SCA7. In adults, this vision loss may come on before the ataxia. If the trinucleotide repeat is long, vision loss can actually come on first In childhood, seizures and heart disease come on with ataxia and vision loss.

Because the rest of the spinocerebellar ataxias are so rare, I’m not going to discuss them in any detail. Most of the time, the symptoms are difficult to distinguish from other SCAs that we’ve already covered, but the genetic mutations are different.

For example, SCA8 is looks very much like other SCA, but is unusual in that rather than things getting worse with larger trinucleotide repeats, it’s only problem when there are 80 to 250 repeats. More or less doesn’t seem to create a problem. SCA10 is a pentanucleotide repeat rather than a trinucleotide repeat. Some of these disorders, such as SCA25, have only been described in one family.

Other Spinocerebellar Ataxias

Although spinocerebellar ataxia is uncommon, it important for neurologists and patients to consider this diagnosis if there is a family history of clumsiness. A diagnosis of SCA may have important implications not just for the person immediately affected, but for their entire family as well.

Sources:

Geschwind DH, Perlman S, Figueroa CP, et al. The prevalence and wide clinical spectrum of the spinocerebellar ataxia type 2 trinucleotide repeat in patients with autosomal dominant cerebellar ataxia. Am J Hum Genet 1997; 60:842.

Moseley ML, Benzow KA, Schut LJ, et al. Incidence of dominant spinocerebellar and Friedreich triplet repeats among 361 ataxia families. Neurology 1998; 51:1666.

Ranum LP, Lundgren JK, Schut LJ, et al. Spinocerebellar ataxia type 1 and Machado-Joseph disease: incidence of CAG expansions among adult-onset ataxia patients from 311 families with dominant, recessive, or sporadic ataxia. Am J Hum Genet 1995; 57:603.

Storey E, du Sart D, Shaw JH, et al. Frequency of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Australian patients with spinocerebellar ataxia. Am J Med Genet 2000; 95:351.

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