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Spinocerebellar Ataxia Type 3
- Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is the most common subtype of type 1 autosomal dominant cerebellar ataxia (ADCA type 1; see this term), a neurodegenerative disorder, and is characterized by ataxia, external progressive ophthalmoplegia, and other neurological manifestations.
Synonyms
- Azorean disease of the nervous system
- MJD
- Machado disease
- Machado-Joseph disease
- Nigro-spino-dentatal degeneration with nuclear ophthalmoplegia
- SCA3
Incidence
How common is Spinocerebellar Ataxia Type 3?
- 1-9/100000
- Prevalence is estimated to be 1-2 in 100,000 with significant geographical and ethnic variations.
Inheritance
Autosomal dominant
Age of Onset
- Childhood
- Adult
What causes SCA3?
- The disease is associated with a CAG repeat expansion mutation in the ATXN3 gene (14q21) with anticipation phenomenon. The normal repeat length is 13-41 whereas repeat lengths causing SCA3 are greater than 56.
What are the symptoms of Spinocerebellar Ataxia Type 3?
- SCA3 is divided into 3 forms. SCA3 type 1 (MJD Type 1, see this term) is associated with ataxia, ophthalmoparesis, pyramidal signs such as spasticity and hyperreflexia, and extrapyramidal signs including dystonia and other movement disorders presenting in adolescence.
- SCA3 type 2 (MJD Type 2, see this term) presents in middle adulthood with ataxia, spasticity, and dystonia. SCA3 type 3 (MJD Type 3, see this term) occurs after the age of 40 and includes ophthalmoparesis and anterior horn cell disease, i.e. fasciculations, atrophy, and weakness.
- Parkinsonism can also be a feature of SCA3.
- A likely overlooked but common feature is impairment of temperature sensation involving the entire body.
Very Common Symptoms
- Abnormal pyramidal sign
- Abnormality of extrapyramidal motor function
- Clumsiness
- Delayed speech and language development
- Diplopia
- Dysarthria
- Dystonia
- Hyperreflexia
- Nystagmus
- Progressive cerebellar ataxia
- Progressive external ophthalmoplegia
- Proptosis
- Skeletal muscle atrophy
Occasional Symptoms
- Abnormality of temperature regulation
- Vestibular dysfunction
- Vocal cord paralysis
What is the prognosis?
- Prognosis is poor but patients have been reported to survive for decades after onset of symptoms.
How is this condition diagnosed?
Diagnosis is based on the clinical picture, familial history and ultimately on genetic testing.
What is the Differential diagnosis?
Differential diagnosis is broad and includes other types of SCA which may have similar features.
Antenatal diagnosis
Prenatal diagnosis and pre-manifestation diagnosis in patients with a family history of SCA can be offered.
Genetic counseling
SCA3 follows an autosomal dominant pattern of inheritance with full penetrance and anticipation phenomenon. Genetic counseling is recommended in symptomatic patients or those with a family history of the disorder due to known SCA mutation, and pre-symptomatic testing should be discussed in adults.
What is the Management or treatment?
- In the absence of specific treatments to slow or stop disease progression, care is supportive. For example, parkinsonism, restless legs syndrome, spasticity, sleep disorders and depression can be treated pharmacologically. Dystonia and spasticity can be managed with local botulinum toxin injections. Occupational and physical therapy are essential. Speech therapy may also be of benefit for managing dysarthria.