Jielle Anne Dote August 10, 2010

BIO 139

CASE DISCUSSION:
Spinocerebellar Ataxia Type 6

Proposed Mode of Inheritance

SCA 6, as is common to all SCA diseases, is inherited in an autosomal dominant fashion
and due to CAG repeat expansion in the CACNA1A gene located at the short arm of
chromosome 19 specifically in region one, band three (19p13).

Review of Literature
As confirmed by not only a few researchers, Spinocerebellar Ataxia (SCA) belongs to a
group of diseases called “polyglutamine diseases” in which the disease-associated protein
contains multiple repeats of glutamine beyond a certain boundary. Polyglutamine diseases are
also known as “CAG Triplet Repeat Disorders” because CAG is the codon for Glutamine, an
amino acid. In the case of SCA, the CAG triplet is replicated for around 35, to as much as 50
times, such as in SCA 3.
In the presented case study, the proband has a Spinocerebellar Ataxia Type 6 (SCA 6).
Zhuchenko, et al reported that there were 21 to 27 units of the CAG repeats contained in the
CACNA1A gene, which they also pointed out to be responsible for SCA 6. Zhuchenko further
characterized SCA 6 as “a permanent and progressive cerebellar functional deficit and atrophy
preceded by momentary imbalance and ‘wooziness’.”
Just like Zhucenko, Jodice, et al also proved that small CAG expansions in the
CACNA1A gene can “cause both an intermittent and a progressive permanent cerebellar deficit
in the absence of other mutations” and that it “can exhibit inter-generational changes of allele
size suggesting that they might be prone to a low level of instability.”
Due to cerebellar damages, the affected individual then experiences impairment in the
sensorimotor, thus the association of SCA diseases with poor coordination of hands, speech,
and eye movements.
On the other hand, Planells, et al have also proven in a study that presymptomatic
diagnosis is possible given a pedigree that is large enough. Since SCA diseases’ age of onset is
usually around 40 and above, presymptomatic diagnosis is important to prepare the family that
certain members of the family are most likely to have the disease upon reaching that age.
Laboratory Tests
Ataxia is considered severe when the patient showed noticeable difficulty or inability to
stand or walk without support. Response to acetazolamide is also one of the laboratory tests to
assess the patient’s condition. However, in some cases, acetazolamide response test is skipped
if the patient experiences uncomfortable side effects.
The proband was reported to have begun having episodes of dizziness and ataxia at the
age of 42. The age of the proband at the conduct of the study was not indicated in the paper.
She also complained of positional vertigo requiring her to sleep with several pillows. After a
year, she noticed mild interictal imbalance. It was also found out later that tandem walking was
impaired, although limb coordination was normal. She has also taken 250 mg acetazolamide
twice daily for three years with continued good response. Members of the pedigree also
exhibited interictal hyperreflexia and spasticity, extracerebellar signs commonly seen with other
SCA syndromes. It was noted that the affected family members exhibited slowly progressive
ataxia. Finally, brain MRI scan was not done on the proband and to the other affected family
members. Brain MRI will help in determining frequency of cerebellar atrophy.

Conclusion
Based on the pedigree and the data gathered, SCA 6, just like all the other SCA
diseases, is a hereditary disease. Specifically, the disease is due to 21 to 27 units of repeats of
CAG in the CACNA1A gene located in chromosome 19p13.

References:
Jen, JC., et. al. Spinocerebellar ataxia type 6 with positional vertigo and acetazolamide
responsive episodic ataxia. J Neurol Neurosurg Psychiatry 1998;65:565–568
Jodice, C. et al. Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6)
due to CAG repeat expansion in the CACNA1A gene on chromosome 19p. Human Molecular
Genetics, 1997, Vol. 6, No. 11 1973–1978.
Planells, JG. et al. Genetics of the SCA6 gene in a large family segregating an
autosomal dominant “pure’’ cerebellar ataxia. J Med. Genet. 1999;36:148–151
Zhuchenko O. et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small
polyglutamine expansions in the á1A-voltage-dependent calcium channel. Nat. Genet.
1997;15:62–9.