Map of Ataxias
There are many types of ataxias, and different criteria can be used for their classification. On this page, we will try to organize the most relevant ataxias by mode of inheritance.
The following figure is a simplified classification without much scientific rigor, for educational purposes only.
Here, ataxias were initially classified into three major groups:
Then, hereditary ataxias were subdivided into four groups , depending on the form of inheritance of the disease :
1. Hereditary ataxias
1.1. Autosomal recessive ataxias
In autosomal recessive ataxias, both parents must carry a mutated gene and pass it on for the child to be affected and develop the disease. In these cases, the parents are carriers of the mutation and do not show symptoms, since the disease only manifests when there are two copies of the altered gene.
So far, the genes associated with various types of genetically based ataxias with autosomal recessive inheritance have been mapped.
Below are some examples.
Friedreich’s Ataxia – FXN gene
Location: Chromosome 9, band 9q21.11. The mutations (usually GAA repeat expansions in the first intron) affect the expression of the frataxin protein.
Ataxia with Vitamin E Deficiency (AVED) – TTPA gene
Location: Chromosome 8, band 8q13. This gene encodes the alpha-tocopherol transfer protein, essential for the transport of vitamin E.
Ataxia Telangiectasia – ATM gene
Location: Chromosome 11, band 11q22.3. The ATM gene plays a key role in the cellular response to DNA damage; its deficiency results in genomic instability and radiation sensitivity.
Location: Chromosome 4, band 4q34.3. A recently discovered intronic repeat expansion in the RFC1 gene has been associated with this clinical picture of ataxia, neuropathy, and vestibular areflexia.
Ataxia with Oculomotor Apraxia (AOA)
There are different types of AOA:
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AOA1: related to the APTX gene on Chromosome 9
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AOA2: related to the SETX gene on Chromosome 9
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AOA4: related to the PNKP gene on Chromosome 19
Autosomal Recessive Spinocerebellar Ataxia Type 8 (SCAR8) – SYNE1 gene
Location: Chromosome 6, band 6q25. The SYNE1 gene is one of the largest in the genome and encodes a protein important for nuclear structure; its mutations are associated with recessive forms of ataxia.
Autosomal Recessive Spinocerebellar Ataxia Type 9 (SCAR9) – Coenzyme Q10 Deficiency – ADCK3 gene
Location: Chromosome 1, band 1p36 (some sources specify 1p36.11). Alterations in ADCK3 impair the biosynthesis of coenzyme Q10, affecting mitochondrial function.
Charlevoix-Saguenay Ataxia (ARSACS) – SACS gene
Location: Chromosome 13, band 13q12.12. Mutations in the SACS gene, which encodes sacsin, are involved in the development of this childhood-onset neurodegenerative ataxia.
Ataxia Associated with Niemann-Pick Disease Type C (NPC)
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NPC1 gene – Location: Chromosome 18, region 18q11–q12
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NPC2 gene – Location: Chromosome 14, region 14q24.3
The following figure shows some examples of ataxias with autosomal recessive inheritance.
About ARSACS (Charlevoix-Saguenay Ataxia)
ARSACS ataxia, also known as Charlevoix-Saguenay spastic ataxia, is a genetic neurodegenerative condition characterized by progressive symptoms of ataxia (loss of motor coordination), spasticity (muscle stiffness), and peripheral neuropathy (peripheral nerve impairment). This ataxia was first identified in populations of the Charlevoix-Saguenay region of Quebec, Canada, and has a particularly high incidence in this region due to a founder effect, where the original mutation spread among descendants of a limited group of settlers.
ARSACS is inherited as an autosomal recessive disorder and is caused by mutations in the SACS gene, which provides instructions for producing a protein called sacsin . Sacsin plays an essential role in the function and maintenance of nerve cells, particularly in cytoskeletal organization and mitochondrial metabolism, which are crucial for neuronal health. A mutation in the SACS gene causes sacsin dysfunction, affecting the structural integrity and function of specific neurons, particularly those in the cerebellum (the region of the brain that coordinates voluntary movement) and central motor pathways. This impairment results in the progressive difficulty with motor coordination observed in patients.
Symptoms of ARSACS ataxia typically begin in infancy, around 12–18 months, with an uncoordinated gait and motor difficulties. As the disease progresses, other symptoms include:
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Progressive ataxia: Loss of balance and coordination of movements that gradually affects walking and control of the arms and legs.
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Spasticity: Muscle stiffness, especially in the lower limbs, which contributes to a characteristic, difficult gait.
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Peripheral neuropathy: Abnormal sensations, such as tingling and numbness, that can affect fine motor control and sensation.
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Ophthalmological changes: Such as nystagmus (involuntary eye movements) and optic atrophy, which can compromise vision over time.
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Retinal dysmorphism: Often detectable on imaging tests, it serves as an additional diagnostic sign, especially in cases where the mutation in the SACS gene is confirmed.
Symptoms progress over years, and patients often require assistance walking or even a wheelchair in later stages. While there is no cure for ARSACS, physical therapy, rehabilitation, and treatments to manage symptoms (such as spasticity and neuropathy) can help improve patients' quality of life.
Learn more about ARSACS
About Spinocerebellar Autosomal Recessive Ataxia Type 8 (SCAR8)
Ataxia related to the SYNE1 gene is known as Spinocerebellar Ataxia Autosomal Recessive Type 8 (SCAR8). The inheritance pattern is autosomal recessive (two mutated copies of the gene must be inherited, one from each parent). The SYNE1 mutation affects proteins essential for the structure and normal function of the nuclear membrane in cells, especially in motor neurons and cerebellar cells.
Main clinical features:
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Progressive cerebellar ataxia (difficulty with motor coordination)
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Dysarthria (slurred speech)
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Difficulties with walking and balance
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In some cases, extracerebellar signs may also occur (e.g., muscle weakness, peripheral neuropathy, mild cognitive impairment).
Age of onset: SCAR8 symptoms usually manifest in childhood, adolescence, or early adulthood, but there is variability.
SCAR8 can vary in severity: some patients have predominantly cerebellar symptoms, while others have mixed signs (cerebellar and pyramidal). Progression is usually slow, and many patients retain the ability to walk for years after the onset of symptoms.
Learn more about SCAR8
About Niemann-Pick Disease Type C
Niemann-Pick disease type C (NPC) is a rare and progressive genetic disorder with autosomal recessive inheritance, caused by mutations in the NPC1 gene (in the vast majority of cases) or NPC2. NPC progresses slowly and currently has no cure. In 2024, a drug was approved by the FDA for NPC—see the Note below.
The disease causes problems in cholesterol and fat processing. The NPC1 and NPC2 genes produce proteins involved in the transport of lipids (mainly cholesterol and sphingolipids) within cells. When these genes are mutated, the transport is impaired, leading to abnormal accumulation of lipids in lysosomes—cellular structures responsible for degrading substances.
Niemann-Pick disease includes types A, B, and C, but the term “Niemann-Pick” is now mainly used to refer to type C, since types A and B are more accurately named sphingomyelinase deficiency, as they result from mutations in the SMPD1 gene, which affects the sphingomyelinase enzyme.
Although the letter "C" in NPC does not refer to the cerebellum, the cerebellum is heavily affected in NPC, and many of the neurological manifestations are due to cerebellar degeneration, such as:
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Ataxia (difficulty with motor coordination)
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Balance problems
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Slurred or scanning speech
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Oculomotor abnormalities (also involving the cerebellum)
NPC can present at any stage of life, but symptoms are often detected in childhood due to school-related difficulties (e.g., cognitive delay, trouble with writing), as well as typical cerebellar ataxia symptoms (poor coordination, balance issues, dysarthria, dysphagia), and in some cases, epilepsy and dystonia. Progressive dementia or psychiatric symptoms may also occur in affected individuals. The compound β-cyclodextrin appears to have good potential for treatment.
Note: In September 2024, the FDA approved the drug Levacetylleucine (Aqneursa) by IntraBio for the treatment of Niemann-Pick Disease Type C (NPC) in both adults and children.
For more information, see: https://www.aqneursa.com/
This is the second drug approved for NPC—the first was Arimoclomol (Miplyffa) by Zevra Therapeutics.
For more information on NPC, see:
1.2. Autosomal dominant ataxias
In ataxias with autosomal dominant transmission, the presence of a mutation in just one copy of a gene is sufficient for the disease to manifest. In other words, typically one of the parents carries the mutation and passes it on to future generations. These diseases usually begin in adulthood, but they may also have an early onset (before age 20) when a genetic phenomenon known as “anticipation” occurs. In ataxias where this phenomenon is present, symptoms may appear earlier and more severely in successive generations of the same family.
1.2.1. Spinocerebellar Ataxias (SCAs)
An important group within the dominantly inherited hereditary ataxias is the SCAs, or spinocerebellar ataxias. As the name suggests, the main parts of the central nervous system (CNS) affected are the cerebellum and, in some cases, the spinal cord (although other areas of the CNS may also be involved in certain SCAs). Spinocerebellar Ataxia Type 3 (SCA3), also known as Machado-Joseph Disease (MJD), is the most common dominantly inherited ataxia worldwide. So far, the genes associated with various types of spinocerebellar ataxias with autosomal dominant inheritance have been mapped.
Some examples are listed below:
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SCA1 – gene ATXN1, Chromosome 6p22.3
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SCA2 – gene ATXN2, Chromosome 12q24.12
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SCA3 – gene ATXN3, Chromosome 14q21.1
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SCA4 – gene ZFHX3 (candidate), Chromosome 16q22.3
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SCA5 – gene SPTBN2, Chromosome 11q13.2
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SCA6 – gene CACNA1A, Chromosome 19p13.13
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SCA7 – gene ATXN7, Chromosome 3p21.1
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SCA8 – gene ATXN8, ATXN8OS, Chromosome 13q21.33
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SCA10 – ATXN10, Chromosome 22q13.31
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SCA11 – gene TTBK2, Chromosome 15q21.1
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SCA12 – gene PPP2R2B, Chromosome 5q32
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SCA13 – gene KCNC3, Chromosome 19q13.32
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SCA14 – gene PRKCG, Chromosome 19q13.42
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SCA15/16 – gene ITPR1, Chromosome 3p26.1
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SCA17 – gene TBP, Chromosome 6q27
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SCA18 – gene IFRD1, Chromosome 1q44
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SCA19/22 – gene KCND3, Chromosome 1p13.2
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SCA20 – gene SCA20, Chromosome 11p11.2
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SCA21 – gene TMEM240, Chromosome 1q41
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SCA23 – gene PDYN, Chromosome 20p13
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SCA25 – gene PNPT1, Chromosome 2p16.1
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SCA26 – gene EEF2, Chromosome 19q13.3
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SCA27A/27B – gene FGF14, Chromosome 13q33.1
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SCA28 – gene AFG3L2, Chromosome 18p11.32
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SCA29/30 – gene ITPR1, Chromosome 3p26.1
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SCA31 – gene BEAN1, Chromosome 16q21
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SCA32 – gene SCA32, locus not yet confirmed
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SCA34 – gene ELOVL4, Chromosome 6q14.1
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SCA35 – gene TGM6, Chromosome 20p13
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SCA36 – gene NOP56, Chromosome 20p13
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SCA37 – gene DAB1, Chromosome 1p32.2
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SCA38 – gene ELOVL5, Chromosome 6p12.1
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SCA40 – gene CCDC88C, probable Chromosome 2q32.1
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SCA41 – gene TRPC3, Chromosome 4q27
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SCA42 – gene CACNA1G, Chromosome 17q21.33
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SCA43 – gene MME, Chromosome 3q25.31
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SCA44 – gene GRM1, Chromosome 6q24
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SCA45 – gene FAT2, Chromosome 4q35.2
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SCA46 – gene PLD3, Chromosome 19q13.2
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SCA47 – gene PUM1, Chromosome 1p35.2
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SCA48 – gene STUB1, Chromosome 16p13.3
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SCA49 – gene SAMD9L, Chromosome 7q21.2
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SCA50 – gene NPTX1, Chromosome 17q25.3
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SCA51 – gene THAP11, Chromosome 16q22.1
See the figure below.
1.2.2. Other dominant ataxias
In addition to SCAs, there are other types of ataxias with autosomal dominant transmission, such as Episodic Ataxias (seven different types) and Dentato-Rubro-Pallido-Louisiana Ataxia (DRPLA).
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Dentato-Rubro-Pallido-Luisiana Ataxia (DRPLA) - ATN1 gene.
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Episodic Ataxia Type 1 (EA1) - KCNA1 gene, chromosome 12 (12p13.32)
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Episodic Ataxia Type 2 (EA2) - CACNA1A gene, chromosome 19 (19p13.13)
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Episodic Ataxia Type 3 (EA3) – gene not yet identified.
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Episodic Ataxia Type 4 (EA4) – gene not yet identified.
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Episodic Ataxia Type 5 (EA5) - probable CACNB4 gene, chromosome 2 (2q23.3)
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Episodic Ataxia Type 6 (EA6) - SLC1A3 gene, chromosome 5 (5p13.2)
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Episodic Ataxia Type 7 (EA7) – gene not yet identified.
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Episodic Ataxia Type 8 (EA8) - UBR4 and SPG2 genes (still provisional)
1.3. Ataxias due to mutation in mitochondrial DNA
Another form of ataxia inheritance is when a mutation occurs in mitochondrial DNA. This type of ataxia is transmitted only from mother to child, as illustrated in the figure, due to mitochondrial problems in the maternal eggs caused by mutations in the genes ( image credit: US, National Library of Medicine ).
Mitochondria are components of our cells that produce energy.
The POLG gene encodes the DNA polymerase in mitochondria, which is responsible for replicating the mitochondrial genome. Mutations in this gene are the main cause of several genetic diseases of mitochondrial origin, with varied phenotypes (symptoms) and onset ages ranging from childhood to adulthood.
Image source: AdobeStock_499267271
Mutations in the POLG gene
Mutations in the POLG gene are the most common cause of inherited mitochondrial disorders, and it is estimated that 2% of the population has some type of POLG mutation. The POLG gene encodes mitochondrial DNA polymerase (a protein involved in mitochondrial DNA replication and repair). Mutations in this gene can cause various neurological disorders . Some diseases caused by POLG mutations manifest in childhood, such as mitochondrial DNA depletion syndromes (mtDNA depletions), in which changes in DNA quantity occur, resulting in an inability to generate energy for the body adequately. There are also other syndromes with late-onset symptoms that arise from mitochondrial DNA deletions (mtDNA deletions). Thus, there are several phenotypic manifestations (different types of symptoms) associated with the POLG gene that can appear from childhood to adulthood, as illustrated in the following figure (reviewed by Jaqueline Garrido ) .
Some mutations in the POLG gene can also cause ataxias with recessive or dominant inheritance, such as progressive external ophthalmoplegia (which can have autosomal recessive or dominant transmission).
For more information on disorders associated with the POLG gene, see:
Other examples of mitochondrial ataxias:
Ataxia MERRF
NARP Ataxia
KSS Ataxia (Kearns-Sayre Syndrome)
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Kearns-Sayre syndrome (orphanet)
1.4. X-Linked Hereditary Ataxias
Another category of inherited ataxias is X- linked cerebellar ataxias (XLCA) , which, as the name suggests, are related to mutations in a gene on the X chromosome. X-linked inheritance patterns can have different effects on males and females. In general, these ataxias progress slowly and are more likely to be passed on to male offspring, as females have two copies of the X chromosome, while males only have one. The most common symptoms include hypotonia, intellectual disabilities, developmental delay, ataxia, and other cerebellar symptoms (tremors, dysmetria, etc.).
The X-linked inheritance pattern can be recessive or dominant.
1.4.1. X-linked recessive inheritance pattern
The X-linked recessive inheritance pattern is a specific form of genetic transmission associated with the X chromosome. In this pattern, the expression of a recessive genetic condition occurs when there is a mutation in a gene located on the X chromosome. Transmission follows the following characteristics:
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Males (XY): Males have only one X chromosome. If they inherit an X containing the gene mutation, they will express the associated recessive condition, since they do not have a second X chromosome to compensate for the mutation.
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Females (XX) : Females have two X chromosomes. To express the recessive condition, they must inherit the mutation on both X chromosomes. If they inherit the mutation on only one X chromosome, they are carriers of the condition but usually do not have significant symptoms.
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Transmission: If an affected male (X with mutation) has sons, all his male children will inherit the Y chromosome, making them unaffected. His daughters will inherit their father's X chromosome, making them carriers. If a carrier female has sons, there is a 50% chance that each son will inherit the X chromosome with the mutation and thus be affected.
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Both Parents Are Carriers: If both parents are carriers, there is a 25% chance that a male child will be affected, a 25% chance that a female child will be affected, a 25% chance that a female child will be a carrier, and a 25% chance that a male child will be neither affected nor a carrier.
This inheritance pattern shows a higher prevalence in males for the expression of X-linked recessive conditions, while females are often asymptomatic carriers.
Examples of ataxias with an X-linked recessive inheritance pattern
SCAX1 (X-linked spinocerebellar ataxia-1) is caused by a mutation in the ATP2B3 gene. Transmission is "X-linked autosomal recessive". Just as examples, another genetic disease (not ataxia) with X-linked recessive transmission is Duchenne muscular dystrophy (DMD) which causes progressive muscle weakness due to the absence or defective production of the protein dystrophin.
1.4.2. X-Linked Dominant Inheritance Pattern
The X-linked dominant inheritance pattern is a specific mode of genetic transmission associated with the X chromosome. In this pattern, a dominant genetic condition is expressed when a mutation occurs in a gene located on the X chromosome. Key features include:
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Males (XY): Males have only one X chromosome. If they inherit an X chromosome carrying the dominant mutation, they will express the associated condition.
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Females (XX): Females have two X chromosomes. If they inherit at least one X chromosome with the dominant mutation, they will express the associated condition.
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Transmission:
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An affected male (X with the dominant mutation) passes his Y chromosome—not his X—to all sons; therefore, his sons are unaffected. All his daughters inherit his X chromosome with the mutation and are affected.
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An affected female has a 50 % chance of passing the X chromosome with the mutation to each child, male or female, who will then be affected.
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Both Parents Affected: If both parents are affected, each child has a 50 % chance of inheriting the X chromosome with the dominant mutation and, consequently, being affected.
In summary, in X-linked dominant inheritance, a single mutated copy of the gene on the X chromosome is sufficient to cause the condition, and in females this effect is not compensated for by the second X chromosome.
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Examples of Ataxias with an X-Linked Dominant Inheritance Pattern
FXTAS (Fragile X-Associated Tremor/Ataxia Syndrome) and Fragile X Syndrome are both genetic conditions with X-linked dominant transmission, and both are related to the FMR1 (Fragile X Mental Retardation 1) gene, located on the X chromosome. However, the nature of the mutation differs between them, and thus these two syndromes have distinct clinical features and affect individuals in very different ways.
Fragile X Syndrome
This syndrome is caused by a full mutation (complete expansion) of the FMR1 gene, in which there are over 200 repeats of the CGG trinucleotide sequence. This leads to a deficiency or absence of the FMRP protein, which is essential for neurological development, resulting in intellectual disability, behavioral problems, and other manifestations. It primarily affects children and is the most common inherited cause of intellectual disability. Symptoms include:
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Cognitive impairment (mild to severe intellectual disability)
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Behavioral features such as autism, anxiety, and hyperactivity
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Physical traits such as a long face, large ears, and joint laxity
Fragile X Syndrome is more common in boys (who have only one X chromosome), although girls can also be affected, typically with milder symptoms due to compensation by the second X chromosome. Women may be carriers and present with mild or partial symptoms.
FXTAS
FXTAS (Fragile X-Associated Tremor/Ataxia Syndrome) is caused by a premutation in the FMR1 gene, with a CGG repeat count between 55 and 200—lower than that found in full Fragile X Syndrome. Individuals with a premutation still produce some FMRP protein, but there is an abnormal accumulation of RNA associated with the gene, which can lead to neurotoxicity with aging. FXTAS typically affects older adults, especially men over the age of 50 who are carriers of the premutation.
The main symptoms involve the motor system and include:
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Action tremors and ataxia (difficulty with motor coordination)
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Memory problems, cognitive processing issues, and other executive function impairments
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Neurological symptoms that may progress to parkinsonism or dementia-like features
FXTAS mainly affects male premutation carriers, although some female carriers may also develop symptoms—typically milder and less frequent.
Learn More About Fragile X and FXTAS
2. Acquired ataxias
In addition to hereditary ataxias, there are several ataxias that can be acquired for various reasons, as illustrated below.
Acquired Ataxias
There are several non-hereditary ataxias that can be acquired in different ways. For educational purposes, we will divide acquired ataxias into two categories, as shown in the previous image.
1. Immune-mediated Cerebellar Ataxias
Examples of acquired ataxias caused by autoimmune conditions:
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Post-infectious cerebellitis
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Gluten ataxia (ataxia due to gluten sensitivity)
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Miller-Fisher Syndrome
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Opsoclonus-Myoclonus Syndrome (ataxic form)
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Paraneoplastic Ataxias (Paraneoplastic Cerebellar Degeneration), usually associated with anti-Yo antibodies (mainly in breast and ovarian tumors), anti-Tr (Hodgkin lymphoma), and anti-Hu (lung cancer), as well as less common antibodies such as anti-CV2, anti-Ri, anti-Ma2, and anti-mGluR1 (see more details below).
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Cerebellar ataxia related to anti-GAD antibodies (Anti–Glutamic Acid Decarboxylase), often associated with insulin-dependent diabetes.
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Guillain-Barré Syndrome – may present with sensory ataxia.
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Multiple Sclerosis (MS) – an autoimmune disease in which the immune system attacks the myelin of neurons, may also cause ataxia symptoms.
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Etc.
About Post-Infectious Cerebellitis
Infectious cerebellitis, or cerebellar encephalitis, is an inflammation of the cerebellum usually caused by viral infections, but it can also result from bacterial, fungal, or parasitic infections. When viral in origin, several types of viruses may be responsible for the inflammation (e.g., Varicella-zoster, Epstein-Barr virus (EBV), Enteroviruses, and others). This cerebellar inflammation may cause typical ataxia symptoms such as imbalance, difficulty with fine motor coordination, abnormal eye movements (nystagmus), speech difficulties, tremors, etc. Diagnosis is made through imaging tests, such as MRI, and analysis of cerebrospinal fluid and blood tests to detect viral infections.
Treatment focuses on the underlying cause, using antivirals, antibiotics, or antifungals depending on the cause, along with supportive care to reduce symptoms. Each case is unique, but it is generally important for the patient to be monitored by a neurologist (or a pediatric neurologist, if the patient is a child), and to begin specialized neurological physiotherapy.
In many cases, the immune system is able to fight the virus on its own, and specific antivirals may also be prescribed if the physician considers it appropriate. The prognosis for infectious cerebellitis is generally good, especially in children, who tend to recover well—but it depends on the causative agent and the severity of inflammation.
About Paraneoplastic Ataxias
Paraneoplastic ataxia is a neurological disorder that occurs as an indirect complication of certain types of cancer, without the tumor directly invading the nervous system. This type of acquired ataxia is an example of a paraneoplastic syndrome, a condition in which the immune system mistakenly attacks parts of the nervous system, believing it is targeting the cancer.
In paraneoplastic ataxia, the immune attack affects the cerebellum, the brain region responsible for movement coordination, resulting in symptoms such as:
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Loss of coordination (ataxia)
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Difficulty walking
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Tremors
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Speech and swallowing problems
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Uncoordinated eye movements
Paraneoplastic ataxia is often found in patients with lung, ovarian, and breast cancers, as well as lymphomas.
Early detection of the underlying cancer and treatment of the paraneoplastic condition with immunosuppressants or other therapies may help control symptoms, although neurological damage is often permanent. The main antibodies associated with paraneoplastic ataxias (paraneoplastic cerebellar degeneration) are called onconeural antibodies, produced by the immune system in response to cancer and targeting the nervous system, particularly the cerebellum.
These antibodies serve as biomarkers useful in diagnosing paraneoplastic syndromes. The most common include:
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Anti-Hu (ANNA-1): Associated with lung cancers, especially small cell lung carcinoma, as well as other tumors. Commonly linked to paraneoplastic encephalomyelitis and cerebellar ataxia.
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Anti-Yo (PCA-1): One of the most common antibodies in paraneoplastic ataxias, often found in patients with ovarian or breast cancer. It primarily attacks Purkinje cells in the cerebellum, leading to cerebellar degeneration.
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Anti-Ri (ANNA-2): Associated with breast cancer and small cell lung carcinoma. May cause ataxia, though more commonly linked to encephalomyelitis and opsoclonus-myoclonus syndrome.
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Anti-Tr (DNER): Found in patients with Hodgkin lymphoma, associated with paraneoplastic cerebellar degeneration.
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Anti-CV2/CRMP5: Related to lung tumors (especially small cell carcinoma) and other cancers. May cause ataxia and additional neurological symptoms, such as peripheral neuropathies.
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Anti-mGluR1: Less common, associated with Hodgkin lymphoma and other neoplasms. Affects glutamate receptors in the cerebellum, resulting in cerebellar ataxia.
These antibodies can be detected in blood or cerebrospinal fluid, helping with early diagnosis of paraneoplastic ataxia and possibly revealing the presence of an underlying or hidden malignancy.
About Anti-GAD Ataxia
Anti-GAD (antibody against the enzyme glutamic acid decarboxylase) is associated with GAD, an enzyme involved in the production of GABA (gamma-aminobutyric acid), a key inhibitory neurotransmitter in the central nervous system.
The presence of anti-GAD antibodies is more commonly associated with autoimmune diseases unrelated to cancer, such as type 1 diabetes and Stiff-Person Syndrome, but it can also cause cerebellar ataxia.
When anti-GAD affects the cerebellum, symptoms may include:
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Progressive ataxia (difficulty with motor coordination)
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Tremors
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Gait instability
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Dysarthria (difficulty articulating words)
Although anti-GAD is primarily associated with autoimmune diseases that do not cause ataxia, it may also be found in some cases of paraneoplastic syndromes, especially in patients with diabetes or thymoma.
Treatment generally includes immunosuppressants, such as corticosteroids or intravenous immunoglobulin (IVIg), aiming to reduce the autoimmune response.
About Gluten Ataxia
In particular, ataxia acquired due to gluten intolerance is an autoimmune disease caused by the ingestion of gluten in individuals who are genetically unable to tolerate this substance. It should be considered as a differential diagnosis for all patients presenting with idiopathic sporadic ataxia symptoms.
Learn More About Gluten Ataxia
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All About Gluten Ataxia – NAF Webinar presented by Dr. Marios Hadjivassiliou on June 12th, 2025
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What You Should Know About Gluten-Induced Ataxia (in Portuguese)
References on Autoimmune Ataxias (NAF – National Ataxia Foundation)
2. Other examples of acquired ataxias
As illustrated in the figure above, there are many other ways to acquire ataxia symptoms. Here are some examples.
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Ataxias due to malformation of the cerebellum
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Ataxias caused by stroke (cerebrovascular accident).
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Ataxia caused by damage to the cerebellum due to accidents in general (e.g. car crash, etc.).
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Acquired ataxias due to alcohol abuse
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Acquired ataxias due to heavy metal poisoning.
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Acquired ataxias due to vitamin deficiency (E, B1, B12).
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Ataxias acquired by certain medications: “Long-term use of some barbiturates such as phenobarbital (an anticonvulsant), and sedatives such as benzodiazepines (“Benzos”) can cause ataxia, as can chronic use of anti-epilepsy drugs (such as phenytoin) and some types of chemotherapy. Source: Mayo Clinic .”
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Symptoms of ataxias can also have psychogenic or functional causes.
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etc.
Learn more about acquired ataxias
3. Idiopathic ataxias
The expression "idiopathic ataxia" is generally used in cases where doctors do not know the reason why a person is experiencing symptoms of ataxia (in other words, the cause is unknown).
MSA (Multiple System Atrophy)
An important example of ataxia classified as "idiopathic" is Multiple System Atrophy (MSA). MSA is a rare degenerative disease that can cause a wide variety of symptoms. There are two main types: MSA-P (the Parkinsonian type) and MSA-C (the Cerebellar type). The disease can cause autonomic dysfunctions, such as urinary incontinence and orthostatic hypotension (a significant drop in blood pressure upon standing). Other common symptoms include abnormal eye movements, sleep disorders, balance problems, speech difficulties (dysarthria), and motor coordination issues. Parkinsonism symptoms, such as tremors and rigidity, are more common in MSA-P, whereas gait ataxia and dysarthria are more frequent in MSA-C. The average age of symptom onset is estimated at 56 ± 10 years for MSA-P and 54.7 ± 8.5 years for MSA-C. The exact cause of MSA is still unknown, which is why it is classified, in the context of ataxias, as a sporadic condition (genetic or environmental factors causing the disease have not yet been identified).
Learn more about MSA:
ILOCA
ILOCA (Idiopathic Late-Onset Cerebellar Ataxia) is a form of ataxia that typically develops later in life and whose cause is not well understood. ILOCA is characterized by progressive damage to the cerebellum, the part of the brain responsible for coordination, balance, and fine motor skills. Symptoms of ILOCA include difficulty walking, balance issues, speech problems, and impaired motor function, and these symptoms tend to worsen over time. The progression of the disease can vary—some cases remain stable for a period, while others worsen progressively. Treatment usually focuses on symptom management through physical, occupational, and speech therapy. ILOCA, when no clear genetic or environmental cause is yet identified, is classified as idiopathic (of unknown origin). However, as new genetic mutations are discovered, some cases of ataxia previously considered idiopathic may be reclassified as hereditary (genetic-based). See the note below.
Note: Many idiopathic ataxias (i.e., ataxias of unknown cause) may in fact be hereditary, but the causative genes are not yet known. Over time, the tendency is for the causes of many idiopathic ataxias to be identified, allowing patients to be reclassified into one of the categories of ataxias with known origins. For example, repeat expansions in intronic regions (non-coding regions) of the RFC1 and FGF14 genes have recently emerged as common causes of late-onset ataxias (LOCAs).
Therefore, in terms of diagnostic strategy, it is recommended to prioritize genetic testing for the following:
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SCA27B (caused by mutations in the FGF14 gene)
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CANVAS (Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome, caused by mutations in the RFC1 gene)
These are currently considered the most common known genetic causes of LOCAs.
Learn more about ILOCA
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ILOCA (Idiopathic Late-Onset Cerebellar Atrophy) (in Portuguese)
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Idiopathic Late-Onset Cerebellar Ataxia (ILOCA) and Cerebellar Plus Syndrome
In some sources, certain ataxias with no known cause (and no evidence of being inherited) are also referred to as "sporadic ataxias", which may lead to some terminological confusion.