The Spinocerebellar ataxia Belongs to a group of genetic disorders that stands out for a lack of coordination of the march that progressively worsens through the years.
He also frequently presents poor coordination of hands, speech and eye movements, probably due to atrophy of the cerebellum; Although sometimes the spinal cord Is also affected.
More specifically, it includes the dorsal column and spinocerebellar extensions, cells of the anterior horn, bridge nuclei, lower olive, basal ganglia, and even part of the cerebral cortex.
In this disease it has been difficult to reliably differentiate their entities, since there are different clinical manifestations within the same family, even between individual subjects.
This disorder is highly dependent on Type of ataxia That is, so that some types can progress faster than others. This is observed through brain scanners, the subject presenting an atrophy of the cerebellum increasingly visible as the disease progresses.
This type of ataxia is inherited, both with a pattern Autosomal dominant like one Autosomal recessive ; And several chromosomes with different mechanisms may be involved depending on the subtype. Although it can also occur in families with no previous history of spinocerebellar ataxia.
It usually appears in early adulthood, after age 18.
Types of spinocerebellar ataxia
Hereditary ataxias are classified by inheritance type and the causative gene or chromosomal locus.
Harding in 1981 was devoted to evaluating several families who presented Cerebellar ataxia Autosomal dominant. However, hereditary ataxia had already been described without penetrating the genetic aspects by Sanger Brown in 1892 and Pierre Marie in 1893.
The first gene related to this ataxia was discovered in 1993, called ATXN1; The disease being classified as"spinocerebellar ataxia type 1"or"SCA1". As other additional dominant genes were later found, they were defined as SCA2, SCA3, etc. It should be noted that the number of the spinocerebellar ataxia type was consistent with the order in which new genes were discovered.
In fact, there are currently about 40 recognized types of spinocerebellar ataxia due to different genetic mutations. In addition, the number continues to increase as there are other occurrences of this disease where the exact genes involved have not yet been found.
Normally the most frequent and defined subtypes are SCA1, SCA2 and SCA3:
SCA type 1 : Inherited by an autosomal dominant pattern. The affected gene is located on chromosome 6. This subtype is characterized because the cerebellum goes through a process of degeneration, and is more common in patients 30 years or more; Dividing equally between both sexes.
First it will be observed that the coordination of the hands is affected, as well as difficulties to maintain the balance when walking. Difficulties in speaking and swallowing also appear.
- SCA type 2 : According to Sullivan Smith et al. (2004) the mutated gene is on chromosome 12, and differs from the others in that its appearance is later, being between the 40 or 50 years.
On the other hand, it is characterized by the slow movements of the eyes and diminution of the reflexes; Being able to study in parallel with another disease as Parkinson's or dementia .
- SCA type 3 or Machado-Joseph disease Appears to be the most common type (21%). It is distinguished by dystonia (alterations in muscle tone, impairing movements), appearance of bulging eyes, double vision, symptoms typical of Parkinson's disease (but not present) and fatigue during the day from having trouble sleeping. It appears that the affected gene is located on chromosome 14.
The most common types are SCA6, 7 and 8; Being the rest very rare.
On the other hand, Harding's 1981 classification focused on clinical manifestations of autosomal dominant cerebellar ataxia (ACAD), and included:
- ACAD I : Manifested by several randomly distributed features such as optic atrophy, dementia, muscular atrophy, Ophthalmoplegia , etc.
- ACAD II : Accompanied by retinitis pigmentosa (loss of visual acuity of the genetic type), as well as extrapyramidal (motor) characteristics, dementia and ophthalmoplegia.
- ACAD III : Would be the so-called"pure cerebellar syndrome".
Four types linked to the X chromosome have also been discovered: 302500, 302600, 301790, and 301840.
It is distinctive of this disorder how, in the same family, there are many different manifestations and genes involved. In addition, because of the evident overlap of symptoms, the only way to know what subtype a patient is in would be testing DNA (And this is only identified in 60% of the patients, in the rest it is not known where the affected part is).
What are its causes?
The causes of spinocerebellar ataxia are linked to hereditary familial transmission. Being able to have an autosomal dominant pattern of inheritance, in which the affected person inherits a healthy gene from one parent and another defective from another parent; Or an autosomal recessive pattern in which the two parents transmit the mutated gene.
Most cases present the first pattern, while less frequent is the second type; Which encompasses the Friedreich's ataxia .
In the spinocerebellar ataxia are present faults in the genetic code or DNA of the person. More specifically, they appear to fall into a type of disease called"polyglutamine diseases"or polyQ, which arise when polyglutamine, which is a repetition of the amino acid glutamine, is repeated more times than normal.
The Glutamine Is a substance that is part of proteins called ataxins, which appear to be very important in spinocerebellar ataxia.
This type of disease can also be called"repetitive CAG triplet disorders"since CAG is the nucleotide triplet, responsible for the encoding of glutamine.
Families with autosomal dominant cerebellar ataxia (ACAD) would constitute 60% to 80%. In turn, 12% do not have a family history of the disease, although they are carriers of mutated genes that could transmit to their offspring.
Studies are still ongoing to determine further genetic mutations associated with spinocerebellar ataxia.
What are your symptoms?
It is important to note that the symptoms of the disease vary according to the type of spinocerebellar ataxia of which we speak and also according to each patient.
In a study by Rossi et al. (2014) a review of a large number of bibliographies was performed to collect the common clinical signs and symptoms of spinocerebellar ataxia. They found:
- That the mean age of onset was 35 years
- That gait ataxia was the most common sign in 68% of cases
- That other symptoms not associated with ataxia were given by 50%.
At the beginning of the disease, some types of spinocerebellar ataxia were: visual impairment, parkinsonism or myoclonus (non-voluntary and sudden shaking of some part of the body). During the illness the most frequent symptoms are dysarthria (90% of the affected ones) and alterations in the movement of the eyes (69%).
Let's delineate in more detail the symptoms of this condition:
- The affected one walks with the legs open, presenting / displaying stagger and instability. It is typical for the body to swing back and forth and trip.
- Clumsy, spasmodic and hesitant movements of the body due to problems in the fine motor of the muscles.
- Problems in the articulation of the language , Which cause speech slowed down and sometimes difficulties in swallowing.
- Ocultomotor dysfunctions
- Pigmentary retinopathy (loss of progressive visual acuity in darker sites and peripheral visual field).
- Nystagmus or short, non-voluntary eye movements
- Motor deterioration that goes in progression, increasing slowly as time passes.
- Practically on most occasions, the family history of hereditary Phenotype Varies within the same family.
- Despite the progressive loss of movement, intellectual capacity is not affected.
- Peripheral neuropathy .
In conclusion, these ataxies cover a wide range of manifestations; Curiously with very frequent related non-ataxic symptoms.
How is it diagnosed?
It should be checked that the patient presents / displays a great part of the symptoms listed above observing how his postural control is, if he can direct his muscles correctly, how he walks, if he presents problems for the speech, the movements of the eyes, etc.
- Neurological examination .
- Images obtained by brain scanner : As pictures by magnetic resonance (RM) or Computed tomography (CT), will manifest a significant atrophy or reduction of the cerebellum that grows as the disease progresses. It is usually (but not always) an olivopontocerebellar atrophy (OPCA).
- Genetic testing : As we have seen, this disease can have a great variability of the symptoms according to the type that is or the degree of advance. Therefore, the best way to know what type it is is doing DNA analysis.
However, these tests will not be useful in all cases, since, as we mentioned, only about 60% of the patients are genetically mutated. Therefore, a person with this disease may not get anything out of the ordinary in a genetic test, because the affected genes are not yet fully known.
However, this type of test is not enough for someone who has had a family history of spinocerebellar ataxia and has children (or wants to have them) to know if they are carriers of affected genes.
According to Sun, Lu & Wu, (2016) it is very useful to establish a relationship between the genes involved and the associated signs and symptoms (what they call a relationship between genotype and phenotype) because this makes diagnosis simple, prediction Course of the disease and monitoring of possible symptoms.
What is your forecast?
The course of the disease depends on several factors such as its causes, types or the age of onset. If it appears early is more negative because there will be degeneration for more years, but if it is later will not be so severe.
Usually, patients with spinocerebellar ataxia will progress to some degree of reliance on other people to perform their daily activities. In the most severe case they may end up in wheelchairs.
Both at the onset of symptoms and the duration of the disease may be subject to variation. If the disease is caused by a polyglutamine it will produce an earlier onset and a more radical progression of clinical symptoms.
What treatment do you have?
There is currently no treatment to cure spinocerebellar ataxia. In fact, this condition is irreversible and is progressing more and more. Therefore, the interventions are focused on alleviating the symptoms caused by the disease and prevent as much as possible that it continues to develop. There are several methods to help those affected:
- Physiotherapy : Where the patient can carry out a series of exercises with the aim of strengthening his muscles.
- Occupational Therapy : To work doing day-to-day activities.
- Special devices and devices So that the person reaches the desired level of independence, being able to fend for itself.
Here we will use a multitude of instruments such as wheelchairs, walking sticks, crutches, walkers, etc. To facilitate the movement; Appliances for writing, personal care or food if there is poor eye-hand coordination; Or even some that facilitate in speech for those who have difficulties in that aspect.
Now with the development of new technologies, there are numerous mobile devices and applications that can be very useful for these people.
- They are also used Drugs , Mainly for non-ataxic symptoms associated with this disease such as tremors, muscle stiffness, depression , sleep disorders , etc.
- Stem Cell Treatment : Is under investigation and is not widespread, but it seems to be a breakthrough in the treatment of spinocerebellar ataxia. The procedure is to transplant mother cells Through lumbar puncture, resulting in a significant improvement in the quality of life of the patients. With this, the tremors are significantly reduced and the walking capacity is considerably increased.
References
- Ataxias and Cerebellar or Spinocerebellar Degeneration Information Page . (February 19, 2016). Retrieved from National Institute of Neurological Disorders and Stroke
- Brown's ataxia (Sanger Brown) . (S.f.). Retrieved on July 5, 2016, from Whonamedit
- Harding, A.E. (1981). Early onset cerebellar ataxia with retained tendon reflexes: a clinical and genetic study of a distinct disorder from Friedreich's ataxia. Journal of Neurology, Neurosurgery, and Psychiatry; 44 (6): 503-508.
- Rossi, M., Perez-Lloret, S., Doldan, L., Cerquetti, D., Balej, J., Millar Vernetti, P., &... Merello, M. (2014). Autosomal dominant cerebellar ataxias: a systematic review of clinical features. European Journal Of Neurology, 21 (4), 607-615.
- Schmitz-Hübsch, T. (May 27, 2006). Clinical assessment of a patient with spinocerebellar ataxia, the challenge of clinical research. Retrieved from University Clinic Bonn, Germany, Department of Neurology.
- Spinocerebellar Ataxia . (S.f.). Retrieved on July 5, 2016.
- Spinocerebellar Ataxia (SCA). (November 2010). Obtained from Muscular Dystrophy.
- Sullivan Smith, C., Michelson, S., & Bennett, R. & (November 2004). Spinocerebellar Ataxia: Making an Informed Choice About Genetic Testing. Retrieved from Medical Genetics and Neurology, University of Washington.
- Sun, Y., Lu, C., & Wu, Z. (2016). Spinocerebellar ataxia: relationship between phenotype and genotype-A Review. Clinical Genetics .