Ataxia with Oculomotor Apraxia Type 2

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Disease Profile

US Estimated

Europe Estimated

Age of onset

Adolescent

ICD-10

G60.2

Inheritance

Spinocerebellar ataxia with axonal neuropathy type 2 is inherited in an autosomal recessive manner.^[2] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

25% (1 in 4) chance to be affected
50% (1 in 2) chance to be an unaffected carrier like each parent
25% chance to be unaffected and not be a carrier

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

AOA2; SCAN 2; SCAR1;

Summary

Ataxia with oculomotor apraxia type 2 (AOA2) is a rare condition that affects muscle control and coordination. Ataxia (difficulty coordinating movements) is generally the earliest sign of the condition and is often diagnosed between age seven and 25 years. Other signs and symptoms may include sensorimotor neuropathy, mild cognitive impairment and less commonly, movement disorders. Approximately half of affected people also experience, oculomotor apraxia which makes it difficult to move the eyes from side-to side in the desired direction. AOA2 is caused by changes (mutations) in the SETX gene and is inherited in an autosomal recessive manner.^[1]^[2]^[3] Treatment is based on the signs and symptoms present in each person.^[2]

Symptoms

The signs and symptoms of ataxia with oculomotor apraxia type 2 (AOA2) generally become apparent between age 7 and twenty five years. Ataxia is often the first symptom and is a major cause of disability in the early stages of the condition. Most people with AOA2 also experience sensorimotor neuropathy which is associated with a decreased ability to move or feel (sensation) in certain parts of the body, especially the lower limbs. Other symptoms can include oculomotor apraxia, movement disorders, and mild cognitive impairment.^[2]^[3]^[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Areflexia	Absent tendon reflexes	0001284
Ataxia		0001251
Cerebellar vermis atrophy		0006855
Sensorimotor neuropathy	Nerve damage causing decreased feeling and movement	0007141
30%-79% of people have these symptoms
Elevated alpha-fetoprotein		0006254
Gait imbalance	Abnormality of balance Abnormality of equilibrium Imbalanced walk [ more ]	0002141
Gaze-evoked nystagmus		0000640
Oculomotor apraxia		0000657
Saccadic smooth pursuit		0001152
Sensory impairment		0003474
5%-29% of people have these symptoms
Babinski sign		0003487
Choreoathetosis		0001266
Conjunctival telangiectasia	Small dilated blood vessels near membrane covering front of eye and eyelids	0000524
Dysphagia	Poor swallowing Swallowing difficulty Swallowing difficulties [ more ]	0002015
Dystonia		0001332
Elevated serum creatine kinase	Elevated blood creatine phosphokinase Elevated circulating creatine phosphokinase Elevated creatine kinase Elevated serum CPK Elevated serum creatine phosphokinase High serum creatine kinase Increased CPK Increased creatine kinase Increased creatine phosphokinase Increased serum CK Increased serum creatine kinase Increased serum creatine phosphokinase [ more ]	0003236
Head tremor		0002346
Hypercholesterolemia	Elevated serum cholesterol Elevated total cholesterol Increased total cholesterol [ more ]	0003124
Hypoalbuminemia	Low blood albumin	0003073
Postural tremor		0002174
Strabismus	Squint eyes Squint Cross-eyed [ more ]	0000486
Urinary bladder sphincter dysfunction		0002839
1%-4% of people have these symptoms
Cerebellar atrophy	Degeneration of cerebellum	0001272
Chorea		0002072
Distal amyotrophy	Distal muscle wasting	0003693
Distal muscle weakness	Weakness of outermost muscles	0002460
Dysarthria	Difficulty articulating speech	0001260
Gait ataxia	Inability to coordinate movements when walking	0002066
Hyporeflexia	Decreased reflex response Decreased reflexes [ more ]	0001265
Impaired distal tactile sensation	Decreased touch sensation in extremities	0006937
Impaired proprioception		0010831
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Peripheral axonal neuropathy		0003477
Pes cavus	High-arched foot	0001761
Scoliosis		0002650
Tremor		0001337
Percent of people who have these symptoms is not available through HPO
Abnormal pyramidal sign		0007256
Autosomal recessive inheritance		0000007
Chronic axonal neuropathy		0007267
Decreased motor nerve conduction velocity		0003431
Impaired distal vibration sensation		0006886
Increased circulating antibody level		0010702
Limb ataxia		0002070
Polyneuropathy	Peripheral nerve disease	0001271
Pontocerebellar atrophy		0006879
Progressive	Worsens with time	0003676
Progressive gait ataxia		0007240
Variable expressivity		0003828

Do you have updated information on this disease? We want to hear from you.

Cause

Spinocerebellar ataxia with axonal neuropathy type 2 (SCAN2) is caused by changes (mutations) in the SETX gene, which provides instructions for making a protein that is involved in DNA repair. People with a mutation in SETX make a reduced amount of this important protein. This leads to an accumulation of damaged DNA which can cause cells to become unstable and die. Certain cells in the brain, such as those involved in coordinating movements (the cerebellum), appear to be most affected by cell death because these cells do not copy themselves to replace cells that have been lost. Scientists suspect that the loss of brain cells in the cerebellum causes the many signs and symptoms associated with SCAN2.^[4]

Diagnosis

A diagnosis of spinocerebellar ataxia with axonal neuropathy type 2 is often suspected based on the presence of characteristic signs and symptoms. Additional testing may then be ordered to confirm the diagnosis and to rule out other conditions that are associated with similar features. This testing may include:^[5]^[2]

Imaging studies, such as magnetic resonance imaging (MRI)
Electromyography
Special blood tests
Nerve biopsy
Genetic testing

Treatment

Although there is no cure for spinocerebellar ataxia with axonal neuropathy type 2 (SCAN2), treatments are available to help manage the signs and symptoms of the condition. For example, affected people may benefit from physical therapy and speech therapy. A wheelchair or other devices may be necessary to help maintain mobility. Children with SCAN2 may also need additional help in school since they may have difficulties with reading, writing and other activities. In some cases, a low-cholesterol diet may be recommended.^[2]^[6]

Related diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes Friedreich ataxia, ataxia with vitamin E deficiency, AOA1, ataxia-telangiectasia, ataxia-telangiectasia-like disorder, autosomal recessive spastic ataxia of Charlevoix-Saguenay. Visit the Orphanet disease page for more information.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

National Ataxia Foundation
600 Highway 169 South
Suite 1725
Minneapolis, MN 55426
Telephone: +1-763-553-0020
Fax: +1-763-553-0167
E-mail: [email protected]
Website: https://ataxia.org/

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Ataxia with Oculomotor Apraxia Type 2. This website is maintained by the National Library of Medicine.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

References

Pera J, Lechner S, Biskup S, Strach M, Grodzicki T, Slowik A. Two novel mutations of the SETX gene and ataxia with oculomotor apraxia type 2. Clin Neurol Neurosurg. January 2015; 128:44-46.
Moreira MC & Koenig M. Ataxia with Oculomotor Apraxia Type 2. GeneReviews. 2018; https://www.ncbi.nlm.nih.gov/books/NBK1154.
SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 1. OMIM. August 2016; https://www.omim.org/entry/606002.
ataxia with oculomotor apraxia. Genetics Home Reference. April 2015; https://ghr.nlm.nih.gov/condition/ataxia-with-oculomotor-apraxia.
Mignarri A, Tessa A, Federico A, Santorelli FM, Dotti MT. Ataxia with oculomotor apraxia type 2: not always an easy diagnosis. Neurol Sci. August 2015; 36(8):1505-1507. https://www.ncbi.nlm.nih.gov/pubmed/25787807.
Spinocerebellar ataxia with axonal neuropathy type 2. Orphanet. May 2015; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=64753.

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Adolescent

G60.2

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Treatment

Related diseases

Organizations

Organizations Supporting this Disease

Learn more

Where to Start

In-Depth Information

References

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.