Rare Neurology News

Disease Profile

Autosomal dominant cerebellar ataxia, deafness, and narcolepsy

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.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Adult

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ICD-10

G11.2

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.

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)

ADCADN; ADCA-DN; Autosomal dominant cerebellar ataxia, deafness and narcolepsy;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Nervous System Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 314404

Definition
A rare polymorphic disorder, subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1), characterized by ataxia, sensorineural deafness and narcolepsy with cataplexy and dementia.

Epidemiology
ADCA-DN has been reported in 24 patients to date from Sweden, the United States, Italy and Brazil.

Clinical description
Disease onset occurs in adulthood (from the ages of 30-40) with the onset of cerebellar ataxia, narcolepsy with cataplexy, sensorineural deafness and dementia. Optic atrophy, cataracts, psychosis, depression, sensory neuropathy, pseudobulbar signs, incontinence and limb lymphedema have also been reported but present later in the disease course. Mild brain atrophy with cerebellum involvement is visible with magnetic resonance imaging (MRI).

Etiology
ADCA-DN is caused by a mutation in the DNA methyltransferase (DNMT1) gene located on chromosome 19p13.2. It encodes an enzyme essential for the repression of transcriptional activity in numerous postmitotic cells.

Genetic counseling
ADCA-DN is inherited autosomal dominantly and genetic counseling is possible. Sporadic cases have also been reported.

Visit the Orphanet disease page for more resources.

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
Narcolepsy
0030050
Sensorineural hearing impairment
0000407
30%-79% of people have these symptoms
Abnormality of mitochondrial metabolism
0003287
Optic atrophy
0000648
5%-29% of people have these symptoms
Abnormality of the cerebral white matter
0002500
Abnormality of the cerebrospinal fluid
0002921
Ataxia
0001251
Atrophy/Degeneration affecting the brainstem
0007366
Babinski sign
0003487
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebral atrophy
Degeneration of cerebrum
0002059
Depressivity
Depression
0000716
Dilated third ventricle
0007082
Head tremor
0002346
Hyperreflexia
Increased reflexes
0001347
Memory impairment
Forgetfulness
Memory loss
Memory problems
Poor memory

[ more ]

0002354
Mental deterioration
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline

[ more ]

0001268
Neuronal loss in central nervous system
Loss of brain cells
0002529
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Predominantly lower limb lymphedema
0003550
Primitive reflex
0002476
Pseudobulbar signs
0002200
Psychosis
0000709
Resting tremor
Tremor at rest
0002322
Sensory neuropathy
Damage to nerves that sense feeling
0000763
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Urinary incontinence
Loss of bladder control
0000020
Percent of people who have these symptoms is not available through HPO
Adult onset
Symptoms begin in adulthood
0003581
Autosomal dominant inheritance
0000006
Cataplexy
0002524
Dementia
Dementia, progressive
Progressive dementia

[ more ]

0000726
Excessive daytime somnolence
Excessive daytime sleepiness
More than typical sleepiness during day

[ more ]

0001262
Progressive
Worsens with time
0003676

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

      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.

      In-Depth Information

      • 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 Autosomal dominant cerebellar ataxia, deafness, and narcolepsy. Click on the link to view a sample search on this topic.