OMIM ID:
Spinocerebellar Ataxia 1
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Early manifestations include gaze-evoked nystagmus and saccadic hypermetria. Ophthalmoplegia develops later in the disease process. Some patients experience a decrease in acuity and dyschromatopsia. The ERG shows evidence of generalized rod and cone photoreceptor dysfunction in some patients. Optic atrophy, central scotomas, central RPE changes, retinal arteriolar attenuation, and blepharospasm have also been reported.
Time-domain OCT has revealed microscopic changes in the macula with thinning of the inner-outer segment junction and nuclear layer in areas with RPE hypopigmentation.
Systemic Features
This is a progressive cerebellar syndrome characterized by systems of ataxia, dysarthria, and bulbar palsy. Speech is often scanning and explosive. DTRs can be exaggerated, and dysmetria is common. The mean age of onset is about age 40. Some cognitive decline may occur. Muscle atrophy, and symptoms of peripheral neuropathy can be present. MRI shows atrophy in the cerebellum, spinal cord, and brainstem. There is considerable variation in clinical expression. Individuals with adult onset of symptoms can survive for 10-30 years whereas those with a juvenile-onset often do not live beyond the age of 16 years.
Genetics
Inheritance
This disorder is caused by an expanded CAG repeat in the ataxin-1 gene (ATXN1) at 6p23. It is an autosomal dominant disorder. Alleles with 39-44 or more CAG repeats are likely to be associated with symptoms.
A male bias and the phenomenon of anticipation have been demonstrated in this disorder as in spinocerebellar ataxia 7 (SCA7) (164500), in which affected offspring of males with SCA develop disease earlier and symptoms progress more rapidly than in offspring of females. This is often explained by the fact that males generally transmit a larger number of CAG repeats.
SCA7 (164500), also inherited in an autosomal dominant pattern and caused by expanded CAG repeats on chromosome 3, has many similar ocular and neurologic features.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission