Ataxia Flashcards
What are the clinical features of Friedrichs Ataxia?
Slowly progressive ataxia with onset before 25 years
Dysarthria
Cardiomyopathy (2/3)
Diabetes (1/3)
What is the genetic cause of Friedrichs Ataxia?
FXN gene
Autosomal Recessive
GAA repeats
What are the GAA repeat lengths in Friedrichs Ataxia?
Typical <33
Premutation: 34-65
Pathogenic >66
Reduced penetrance: 44-66
What should you do if you cannot find a second repeat expansion in Friedrichs Ataxia?
Gene sequencing / del / dup analysis (4%)
What are the features of FXTAS
Late-adult–onset neurodegenerative disorder
Affecting primarily male (and occasionally female) carriers of a premutation expansion (55-200 CGG repeats) of the fragile X mental retardation 1 gene (FMR1)
Movement disorder with progressive intention tremor and gait ataxia, with more variable associated features of parkinsonism, dysautonomia, peripheral neuropathy, and dementia
What is the repeat expansion in FXTAS?
CGG
Premutation: 55-200
What is the testing strategy in triplet repeat disorders?
PCR with reflex to southern blot (can tell how much protein in there)
What is the most common cause of type 1 spinocerebellar ataxia?
CAG trinucleotide repeats in ATXN1 and ATXN7
What is ataxia?
Incoordination of Muscle movement
-Gait/ imbalance
-Limbs
-Speech
-Eye movements
What are some of the recessive ataxia?
-Friedreich ataxia (FA)
-Ataxia telangiectasia
-Abetalipoproteinemia
-Ataxia with isolated vitamin E deficiency (AVED)
What is the most common feature of spinocerebellar ataxia?
Cerebellar atrophy
What is the cause of SCA1, 2, 3, 6, 7, 17 and DRPLA?
CAG/polyQ trinucleotide expansion
What is the most common mutation in Friedreich ataxia?
96% of individuals with FRDA, is an abnormally expanded GAA repeat in intron 1 of FXN
Which type of spinocerebellar ataxia has visual impairment?
SCA7
What causes genetic stability in SCA2?
CAA interruptions
