MCID: CRB142
MIFTS: 36

Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Ear diseases, Fetal diseases

Aliases & Classifications for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

MalaCards integrated aliases for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant:

Name: Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant 57 25 75 29 6 73
Adcadn 57 53 25 75
Autosomal Dominant Cerebellar Ataxia-Deafness-Narcolepsy Syndrome 53 25 59
Autosomal Dominant Cerebellar Ataxia, Deafness and Narcolepsy 12 53 15
Adca-Dn Syndrome 53 25 59
Autosomal Dominant Cerebellar Ataxia, Deafness, and Narcolepsy 53 25
Adca-Dn 53

Characteristics:

Orphanet epidemiological data:

59
autosomal dominant cerebellar ataxia-deafness-narcolepsy syndrome
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
adult onset (thirties to forties)
narcolepsy and deafness are the first symptoms


HPO:

32
cerebellar ataxia, deafness, and narcolepsy, autosomal dominant:
Onset and clinical course adult onset progressive
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 314404Disease definitionAutosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is a polymorphic disorder and a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1; see this term) characterized by ataxia, sensorineural deafness and narcolepsy with cataplexy and dementia.EpidemiologyADCA-DN has been reported in 24 patients to date from Sweden, the United States, Italy and Brazil.Clinical descriptionDisease 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).EtiologyADCA-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 counselingADCA-DN is inherited autosomal dominantly and genetic counseling is possible. Sporadic cases have also been reported.Visit the Orphanet disease page for more resources.

MalaCards based summary : Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant, also known as adcadn, is related to narcolepsy and aceruloplasminemia, and has symptoms including cerebellar ataxia, muscle spasticity and excessive daytime somnolence. An important gene associated with Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant is DNMT1 (DNA Methyltransferase 1), and among its related pathways/superpathways is Macrophage Differentiation and Growth Inhibition by METS. Affiliated tissues include brain and cerebellum, and related phenotypes are nystagmus and depressivity

Genetics Home Reference : 25 Autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCADN) is a nervous system disorder with signs and symptoms that usually begin in mid-adulthood and gradually get worse.

OMIM : 57 ADCADN is an autosomal dominant neurologic disorder characterized by adult onset of progressive cerebellar ataxia, narcolepsy/cataplexy, sensorineural deafness, and dementia. More variable features include optic atrophy, sensory neuropathy, psychosis, and depression (summary by Winkelmann et al., 2012). (604121)

UniProtKB/Swiss-Prot : 75 Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant: An autosomal dominant neurologic disorder characterized by adult onset of progressive cerebellar ataxia, narcolepsy, cataplexy, sensorineural deafness, and dementia. More variable features include optic atrophy, sensory neuropathy, psychosis, and depression.

Related Diseases for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

Diseases related to Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 narcolepsy 30.1 DNMT1 HCRT
2 aceruloplasminemia 10.5
3 ataxia-oculomotor apraxia 3 10.5
4 autosomal dominant cerebellar ataxia 10.2
5 neuropathy, hereditary sensory, type ie 10.0 DNMT1 SPTLC1
6 tabes dorsalis 9.8 NAA50 SPTLC1
7 hereditary sensory neuropathy 9.8 DNMT1 SPTLC1
8 tertiary neurosyphilis 9.8 NAA50 SPTLC1
9 neuropathy 9.4 DNMT1 SPTLC1

Graphical network of the top 20 diseases related to Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant:



Diseases related to Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

Symptoms & Phenotypes for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
spasticity
hyperreflexia
dementia
cerebellar atrophy
excessive daytime sleepiness
more
Head And Neck Ears:
sensorineural deafness

Muscle Soft Tissue:
limb lymphedema (in some patients)

Laboratory Abnormalities:
decreased csf hypocretin

Head And Neck Eyes:
optic atrophy (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
depression (in some patients)
psychosis (in some patients)

Neurologic Peripheral Nervous System:
sensorimotor polyneuropathy


Clinical features from OMIM:

604121

Human phenotypes related to Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant:

59 32 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000639
2 depressivity 59 32 occasional (7.5%) Occasional (29-5%) HP:0000716
3 ataxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001251
4 spasticity 59 32 occasional (7.5%) Occasional (29-5%) HP:0001257
5 hyperreflexia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001347
6 cataract 59 32 occasional (7.5%) Occasional (29-5%) HP:0000518
7 sensorineural hearing impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0000407
8 optic atrophy 59 32 occasional (7.5%) Frequent (79-30%) HP:0000648
9 sensory neuropathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0000763
10 babinski sign 59 32 occasional (7.5%) Occasional (29-5%) HP:0003487
11 memory impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0002354
12 abnormality of mitochondrial metabolism 59 32 frequent (33%) Frequent (79-30%) HP:0003287
13 mental deterioration 59 32 occasional (7.5%) Occasional (29-5%) HP:0001268
14 cerebellar atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0001272
15 urinary incontinence 59 32 occasional (7.5%) Occasional (29-5%) HP:0000020
16 abnormality of the cerebrospinal fluid 59 32 occasional (7.5%) Occasional (29-5%) HP:0002921
17 atrophy/degeneration affecting the brainstem 59 32 occasional (7.5%) Occasional (29-5%) HP:0007366
18 head tremor 59 32 occasional (7.5%) Occasional (29-5%) HP:0002346
19 cerebral atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0002059
20 neuronal loss in central nervous system 59 32 occasional (7.5%) Occasional (29-5%) HP:0002529
21 pseudobulbar signs 59 32 occasional (7.5%) Occasional (29-5%) HP:0002200
22 abnormality of the cerebral white matter 59 32 occasional (7.5%) Occasional (29-5%) HP:0002500
23 resting tremor 59 32 occasional (7.5%) Occasional (29-5%) HP:0002322
24 predominantly lower limb lymphedema 59 32 occasional (7.5%) Occasional (29-5%) HP:0003550
25 narcolepsy 59 32 hallmark (90%) Very frequent (99-80%) HP:0030050
26 primitive reflex 59 32 occasional (7.5%) Occasional (29-5%) HP:0002476
27 dilated third ventricle 59 32 occasional (7.5%) Occasional (29-5%) HP:0007082
28 peripheral neuropathy 59 Occasional (29-5%)
29 psychosis 32 occasional (7.5%) HP:0000709
30 dementia 32 HP:0000726
31 excessive daytime sleepiness 32 HP:0002189
32 cataplexy 32 HP:0002524

UMLS symptoms related to Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant:


cerebellar ataxia, muscle spasticity, excessive daytime somnolence, memory loss

Drugs & Therapeutics for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

Search Clinical Trials , NIH Clinical Center for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

Genetic Tests for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

Genetic tests related to Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant:

# Genetic test Affiliating Genes
1 Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant 29 DNMT1

Anatomical Context for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

MalaCards organs/tissues related to Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant:

41
Brain, Cerebellum

Publications for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

Articles related to Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant:

# Title Authors Year
1
Autosomal Dominant Cerebellar Ataxia, Deafness, and Narcolepsy (ADCA-DN) Associated With Progressive Cognitive and Behavioral Deterioration. ( 27869457 )
2016
2
Identification of a methylation profile for DNMT1-associated autosomal dominant cerebellar ataxia, deafness, and narcolepsy. ( 27602171 )
2016
3
Polysomnographic and neurometabolic features may mark preclinical autosomal dominant cerebellar ataxia, deafness, and narcolepsy due to a mutation in the DNA (cytosine-5-)-methyltransferase gene, DNMT1. ( 24709307 )
2014
4
Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. ( 22328086 )
2012
5
Neuroimaging study in autosomal dominant cerebellar ataxia, deafness, and narcolepsy. ( 10599806 )
1999

Variations for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

UniProtKB/Swiss-Prot genetic disease variations for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant:

75
# Symbol AA change Variation ID SNP ID
1 DNMT1 p.Ala554Val VAR_070055 rs397509392
2 DNMT1 p.Gly589Ala VAR_070056 rs397509393
3 DNMT1 p.Val590Phe VAR_070057 rs397509391

ClinVar genetic disease variations for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 DNMT1 NM_001130823.2(DNMT1): c.1816G> T (p.Val606Phe) single nucleotide variant Pathogenic rs397509391 GRCh37 Chromosome 19, 10265278: 10265278
2 DNMT1 NM_001130823.2(DNMT1): c.1816G> T (p.Val606Phe) single nucleotide variant Pathogenic rs397509391 GRCh38 Chromosome 19, 10154602: 10154602
3 DNMT1 NM_001130823.2(DNMT1): c.1709C> T (p.Ala570Val) single nucleotide variant Pathogenic rs397509392 GRCh37 Chromosome 19, 10265385: 10265385
4 DNMT1 NM_001130823.2(DNMT1): c.1709C> T (p.Ala570Val) single nucleotide variant Pathogenic rs397509392 GRCh38 Chromosome 19, 10154709: 10154709
5 DNMT1 NM_001130823.2(DNMT1): c.1814G> C (p.Gly605Ala) single nucleotide variant Pathogenic rs397509393 GRCh37 Chromosome 19, 10265280: 10265280
6 DNMT1 NM_001130823.2(DNMT1): c.1814G> C (p.Gly605Ala) single nucleotide variant Pathogenic rs397509393 GRCh38 Chromosome 19, 10154604: 10154604

Expression for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

Search GEO for disease gene expression data for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant.

Pathways for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

Pathways related to Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.34 DNMT1 HDAC2

GO Terms for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

Molecular functions related to Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity, transferring acyl groups GO:0016746 8.96 NAA50 SPTLC1
2 promoter-specific chromatin binding GO:1990841 8.62 DNMT1 HDAC2

Sources for Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant

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9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
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74 UMLS via Orphanet
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