Rare Neurology News

Disease Profile

Giant axonal neuropathy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

G60.8

Inheritance

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

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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

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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.

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

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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.

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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.

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Not applicable

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Other names (AKA)

GAN1; Giant axonal neuropathy 1; Neuropathy, giant axonal;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Giant axonal neuropathy (GAN) is a neurodegenerative disorder characterized by abnormally large and dysfunctional axons (the specialized extensions of nerve cells that are required for the transmission of nerve impulses). The condition typically appears in infancy or early childhood with severe peripheral motor and sensory neuropathy (affecting movement and sensation in the arms and legs). Early signs include difficulty walking, lack of coordination, and loss of strength. Over time, the central nervous system (brain and spinal cord) becomes involved, causing a gradual decline in mental function, loss of control of body movements, and seizures. Giant axonal neuropathy is caused by mutations in the GAN gene. It follows and autosomal dominant pattern of inheritance.[1][2] Management is directed by a multidisciplinary team with the goal of optimizing intellectual and physical development.[2]

Symptoms

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
Abnormality of the Achilles tendon
0005109
Areflexia
Absent tendon reflexes
0001284
CNS hypomyelination
0003429
Difficulty walking
Difficulty in walking
0002355
Diffuse axonal swelling
0003405
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Joint hypermobility
Double-Jointed
Flexible joints
Increased mobility of joints

[ more ]

0001382
Pili canaliculi
0002235
Proximal muscle weakness
Weakness in muscles of upper arms and upper legs
0003701
30%-79% of people have these symptoms
Abnormal cerebellum morphology
Abnormality of the cerebellum
Cerebellar abnormalities
Cerebellar abnormality
Cerebellar anomaly

[ more ]

0001317
Abnormal hand morphology
Abnormal shape of hand
0005922
Distal muscle weakness
Weakness of outermost muscles
0002460
Distal sensory impairment
Decreased sensation in extremities
0002936
Facial palsy
Bell's palsy
0010628
Intellectual disability
Mental-retardation
Mental retardation, nonspecific
Mental retardation
Mental deficiency

[ more ]

0001249
Pes cavus
High-arched foot
0001761
Scoliosis
0002650
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot

[ more ]

0001762
Unsteady gait
Unsteady walk
0002317
Woolly hair
Kinked hair
0002224
5%-29% of people have these symptoms
Abnormality of the pituitary gland
0012503
Babinski sign
0003487
Falls
0002527
Genu valgum
Knock knees
0002857
Limb muscle weakness
Limb weakness
0003690
Percent of people who have these symptoms is not available through HPO
Abnormal pyramidal sign
0007256
Abnormality of the hand
Abnormal hands
Hand anomalies
Hand deformities

[ more ]

0001155
Areflexia of lower limbs
0002522
Autosomal recessive inheritance
0000007
Curly hair
0002212
Decreased number of peripheral myelinated nerve fibers
0003380
Distal amyotrophy
Distal muscle wasting
0003693
Dysarthria
Difficulty articulating speech
0001260
Hyperreflexia
Increased reflexes
0001347
Hyporeflexia of lower limbs
0002600
Juvenile onset
Signs and symptoms begin before 15 years of age
0003621
Morphological abnormality of the pyramidal tract
0002062
Motor axonal neuropathy
0007002
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Pes planus
Flat feet
Flat foot

[ more ]

0001763
Sensory axonal neuropathy
0003390
Slow progression
Signs and symptoms worsen slowly with time
0003677
Spastic paraplegia
0001258
Steppage gait
High stepping
0003376

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    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

      Organizations Providing General Support

        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

          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.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Giant axonal neuropathy. Click on the link to view a sample search on this topic.

            References

            1. Giant axonal neuropathy. Genetics Home Reference (GHR). October 2007; https://ghr.nlm.nih.gov/condition/giant-axonal-neuropathy. Accessed 6/18/2015.
            2. Kuhlenbäumer G, Timmerman V, Bomont P. Giant Axonal Neuropathy. GeneReviews. October 9, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1136/. Accessed 6/18/2015.