Friedreich Ataxia and Spinocerebellar Ataxias
On this page
Direct answer
Friedreich ataxia is an autosomal recessive degenerative ataxia caused by a GAA trinucleotide repeat expansion in the FXN gene, which reduces frataxin and damages the spinal cord, cerebellum and heart. It usually begins before age 25 with gait ataxia, leg areflexia, extensor plantar responses and dysarthria, often complicated by hypertrophic cardiomyopathy. Spinocerebellar ataxias are mostly autosomal dominant CAG-repeat disorders.
What you must remember
- Genetics: autosomal recessive GAA expansion in intron 1 of FXN on chromosome 9q, with the expanded alleles reducing frataxin production.
- Onset: usually before age 25, with gait and limb ataxia that progress over years.
- Reflex and sensory signs: leg areflexia with extensor plantar responses, plus loss of proprioception and vibration sense.
- Associated features: pes cavus, scoliosis, dysarthria, optic atrophy and sensorineural hearing loss.
- Cardiac disease: hypertrophic cardiomyopathy is common and a leading cause of death, so ECG and echocardiography are essential.
- Diabetes: a minority develop diabetes mellitus, and glucose screening forms part of routine care.
- Spinocerebellar ataxias: mostly autosomal dominant CAG polyglutamine expansions, including SCA1, SCA2, SCA3 and SCA6.
- Anticipation: CAG repeats lengthen across generations, bringing earlier onset and greater severity.
A diagnostic pathway for young-onset ataxia
A 17-year-old boy has had an unsteady gait for two years, with slurred speech and high-arched feet. Examination shows absent ankle reflexes and extensor plantar responses. The pattern suggests a hereditary ataxia, and the steps below narrow the diagnosis.
- Establish the onset and pattern: Onset before age 25 and a recessive pattern direct attention to Friedreich ataxia rather than late-onset disease.
- Examine for pyramidal and sensory signs: Leg areflexia, extensor plantars and proprioceptive loss point to Friedreich ataxia rather than pure cerebellar disease.
- Check the heart: ECG and echocardiography look for hypertrophic cardiomyopathy and arrhythmia, which are common and dangerous.
- Screen for associated features: Check glucose and look for optic atrophy, hearing loss, scoliosis and pes cavus, which accompany the disorder.
- Confirm the genetics: GAA repeat testing of FXN confirms Friedreich ataxia, while CAG repeat testing of the relevant genes (ATXN genes, or CACNA1A for SCA6) is used for dominant SCAs.
- Counsel the family: Recessive inheritance carries a risk to siblings, so carrier testing and counselling are offered to relatives.
Where the exam tries to catch you
Most errors come from matching the family pattern to the wrong gene or ignoring the heart.
- Trap: labelling every young-onset ataxia as Friedreich Correct: Friedreich ataxia has leg areflexia and cardiomyopathy, whereas many SCAs are cerebellar-predominant without these features.
- Trap: ignoring the heart because the picture looks neurological Correct: hypertrophic cardiomyopathy is a leading cause of death, so an ECG and echocardiogram are mandatory.
- Trap: assuming a dominant family history means Friedreich ataxia Correct: Friedreich ataxia is recessive with GAA repeats, while dominant ataxias are usually CAG-repeat disorders, so the right gene must be tested.
Frequently asked questions
What gene and repeat cause Friedreich ataxia?
Friedreich ataxia is caused by a GAA trinucleotide repeat expansion in intron 1 of the FXN gene, which lowers frataxin production. Most affected people carry the expansion on both alleles. Repeat length broadly correlates with age of onset and severity.
Which cardiac finding is most common in Friedreich ataxia?
Hypertrophic cardiomyopathy is the most common cardiac finding in Friedreich ataxia and a leading cause of death. Arrhythmias and conduction abnormalities also occur. Regular ECG and echocardiography are therefore part of routine follow-up.
How does anticipation work in spinocerebellar ataxias?
Anticipation in spinocerebellar ataxias means the CAG repeat tends to lengthen in successive generations, leading to earlier onset and greater severity. The effect is often more marked with paternal transmission in several of these disorders. Repeat expansion is the molecular basis of this phenomenon.
Which features distinguish Friedreich ataxia from cerebellar spinocerebellar ataxias?
Friedreich ataxia typically shows leg areflexia, extensor plantar responses, proprioceptive loss and early cardiomyopathy. Many cerebellar spinocerebellar ataxias present with a more purely cerebellar picture, although clinical overlap exists. Genetic testing resolves cases where the bedside pattern is unclear.
Which spinocerebellar ataxia is the most common dominant ataxia worldwide?
Spinocerebellar ataxia type 3, also called Machado-Joseph disease, is the most common dominant ataxia worldwide. It is caused by a CAG expansion in the ATXN3 gene and produces ataxia with pyramidal and extrapyramidal features. Its diagnosis rests on the family history and repeat testing.