Hereditary Neurodegenerative Ataxias Flashcards
Of the heritable ataxias, the autosomal dominant ones tend to ___ while the recessive ones tend to ___.
Of the heritable ataxias, the autosomal dominant ones tend to be isolated neurologic issues while the recessive ones tend to have systemic involvement.
Substances that may induce a chronic ataxia
Ethanol
Phenytoin
Paraneoplastic cerebellar degeneration
Relatively frequent cause of late-onset ataxia
Characterized by subacute progressive course and requires prompt diagnosis and treatment of the underlying neoplasm.
Vitamin deficiencies and ataxia
B12 deficiency and E deficiency can both cause ataxia
Spinocerebellar ataxias
A group of auotosomal dominant cerebellar ataxias characterized by their genetic loci. Most are due to trinucleotide repeats and some are inherited with anticipation. All of them onset between ages 20-30 (with the notable exception of SCA-6, which is ages 40-50).
There are more than 40 disorders included under this umbrella term.
Definitive diagnosis is made by DNA testing. Clinical phenotype and ethnic/geographi origin are helpful in propritizing genetic testing.
Most common spinocerebellar ataxias (table)
Most trinucleotide repeat disorders involve repetition of the sequence:
CAG
SCA-1
- Autosomal dominant inheritance with anticipation
- Ataxin-1 mutation
- Hyperreflexia, peripheral neuropathy, cognitive impairment
- Occulomotor features:
- Slow, hypermetric saccades
- Sometimes ophthalmoparesis
SCA-2
- Autosomal dominant inheritance with anticipation
- Ataxin-2 mutation
- Differentiated by the development of dementia and slow eye movements
- Hyperreflexia, peripheral neuropathy, cognitive impairment progressing to dementia
- Occulomotor features:
- Slow saccades
- Ophthalmoplegia
SCA-3
- Also known as Machado-Joseph Disease
- Autosomal dominant inheritance with anticipation and variable expression
- Ataxin-3 mutation
- The single most common SCA subtype in most populations
- Features:
- Pure spinocerebellar ataxia
- Familial parkinsonism
- Hereditary spastic paraplegia
- Hereditray neuropathy
- Restless leg syndrome
- Physial exam signs:
- Commonly have impaired temperature recognition in all extremities and the face, which is rather specific for SCA-3.
- Pseudoexophthalmos (blging eyes caused by lid retraction)
- Square wave jerks
- Dystonia
SCA-6
- Autosomal dominant inheritance WITHOUT anticipation
- CACNA1A mutation
- Later age of onset than most SCAs (onset ~40-50)
- Often no family history
- More mild disease course than other SCAs
- Occulomotor features:
- Downward-beating nystagmus
- Saccadic pursuit
SCA-7
- Autosomal dominant inheritance with anticipation
- Ataxin-7 mutation
- Gradually develop blindness
- May present with infantile symptoms
- Occulomotor features:
- Saccadic pursuit
- Slow saccades
SCA-8
- Autosomal dominant inheritance WITHOUT anticipation
- No protein product – located in a 3’UTR
- Hyperreflexia
- Normal life span
- Occulomotor features:
- Nystagmus
- Saccadic pursuit
Diagnostic workup of a spinocerebellar ataxia
- MRI or CT to detect atrophy of the cerebellum (and possibly other subcortical structures)
- Genetic testing guided by clinical features, age of onset, eye movement disorder pattern, and imaging features
MRI showing spinocerebellar ataxia-induced cerebellar degeneration
