ADCADN
MCID: CRB142
MIFTS: 43

Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant (ADCADN)

Categories: Ear diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare 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 56 25 73 29 6 71
Adcadn 56 52 25 73
Autosomal Dominant Cerebellar Ataxia-Deafness-Narcolepsy Syndrome 52 25 58
Autosomal Dominant Cerebellar Ataxia, Deafness and Narcolepsy 12 52 15
Adca-Dn Syndrome 52 25 58
Autosomal Dominant Cerebellar Ataxia, Deafness, and Narcolepsy 52 25
Adca-Dn 52

Characteristics:

Orphanet epidemiological data:

58
autosomal dominant cerebellar ataxia-deafness-narcolepsy syndrome
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

56
Inheritance:
autosomal dominant

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


HPO:

31
cerebellar ataxia, deafness, and narcolepsy, autosomal dominant:
Inheritance autosomal dominant inheritance
Onset and clinical course progressive adult onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare otorhinolaryngological diseases
Developmental anomalies during embryogenesis


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

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. People with ADCADN have difficulty coordinating movements (ataxia) and mild to moderate hearing loss caused by abnormalities of the inner ear (sensorineural deafness). Most have excessive daytime sleepiness (narcolepsy). Narcolepsy is typically accompanied by cataplexy, which is a sudden brief loss of muscle tone in response to strong emotion (such as excitement, surprise, or anger). These episodes of muscle weakness can cause an affected person to slump over or fall, which occasionally leads to injury. These characteristic signs and symptoms of ADCADN typically begin in a person's thirties. Eventually, people with ADCADN also experience a decline of intellectual function (dementia). The cognitive problems often begin with impairment of executive function, which is the ability to plan and implement actions and develop problem-solving strategies. Other features that can occur as the condition worsens include degeneration of the nerves that carry information from the eyes to the brain (optic atrophy); clouding of the lenses of the eyes (cataracts); numbness, tingling, or pain in the arms and legs (sensory neuropathy); puffiness or swelling (lymphedema) of the limbs; an inability to control the bowels or the flow of urine (incontinence); depression; uncontrollable crying or laughing (pseudobulbar signs); or a distorted view of reality (psychosis). Affected individuals usually survive into their forties or fifties.

MalaCards based summary : Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant, also known as adcadn, is related to neuropathy, hereditary sensory, type ie and ataxia and polyneuropathy, adult-onset, and has symptoms including excessive daytime somnolence, memory loss and muscle spasticity. An important gene associated with Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant is DNMT1 (DNA Methyltransferase 1), and among its related pathways/superpathways are Chromatin Regulation / Acetylation and One carbon pool by folate. Affiliated tissues include eye, brain and cerebellum, and related phenotypes are sensorineural hearing impairment and narcolepsy

Disease Ontology : 12 An autosomal dominant cerebellar ataxia that is characterized by ataxia, sensorineal deafness, narcolepsy with cataplexy, and dementia, has material basis in mutation in the DNMT1 gene.

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. 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.

OMIM : 56 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 : 73 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

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

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

58 31 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000407
2 narcolepsy 58 31 hallmark (90%) Very frequent (99-80%) HP:0030050
3 optic atrophy 58 31 occasional (7.5%) Frequent (79-30%) HP:0000648
4 abnormality of mitochondrial metabolism 58 31 frequent (33%) Frequent (79-30%) HP:0003287
5 spasticity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001257
6 hyperreflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001347
7 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
8 depressivity 58 31 occasional (7.5%) Occasional (29-5%) HP:0000716
9 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
10 cataract 58 31 occasional (7.5%) Occasional (29-5%) HP:0000518
11 sensory neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000763
12 memory impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0002354
13 babinski sign 58 31 occasional (7.5%) Occasional (29-5%) HP:0003487
14 abnormality of the cerebral white matter 58 31 occasional (7.5%) Occasional (29-5%) HP:0002500
15 mental deterioration 58 31 occasional (7.5%) Occasional (29-5%) HP:0001268
16 cerebellar atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001272
17 abnormality of the cerebrospinal fluid 58 31 occasional (7.5%) Occasional (29-5%) HP:0002921
18 urinary incontinence 58 31 occasional (7.5%) Occasional (29-5%) HP:0000020
19 atrophy/degeneration affecting the brainstem 58 31 occasional (7.5%) Occasional (29-5%) HP:0007366
20 head tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0002346
21 cerebral atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002059
22 neuronal loss in central nervous system 58 31 occasional (7.5%) Occasional (29-5%) HP:0002529
23 pseudobulbar signs 58 31 occasional (7.5%) Occasional (29-5%) HP:0002200
24 resting tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0002322
25 predominantly lower limb lymphedema 58 31 occasional (7.5%) Occasional (29-5%) HP:0003550
26 primitive reflex 58 31 occasional (7.5%) Occasional (29-5%) HP:0002476
27 dilated third ventricle 58 31 occasional (7.5%) Occasional (29-5%) HP:0007082
28 psychosis 31 occasional (7.5%) HP:0000709
29 peripheral neuropathy 58 Occasional (29-5%)
30 dementia 31 HP:0000726
31 excessive daytime sleepiness 31 HP:0002189
32 cataplexy 31 HP:0002524

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
spasticity
hyperreflexia
dementia
excessive daytime sleepiness
cerebellar atrophy
more
Head And Neck Eyes:
optic atrophy (in some patients)

Muscle Soft Tissue:
limb lymphedema (in some patients)

Laboratory Abnormalities:
decreased csf hypocretin

Head And Neck Ears:
sensorineural deafness

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

Neurologic Peripheral Nervous System:
sensorimotor polyneuropathy

Clinical features from OMIM:

604121

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


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

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased cell death HMECs cells GR00103-A-0 8.92 DNMT1 DNMT3B UHRF1 UHRF2

MGI Mouse Phenotypes related to Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.28 DMAP1 DNMT1 DNMT3B DNMT3L RTN4IP1 UHRF1

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:

40
Eye, Brain, Cerebellum, Breast

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

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

# Title Authors PMID Year
1
Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. 56 6
22328086 2012
2
Autosomal dominant cerebellar ataxia deafness and narcolepsy. 56 6
8747854 1995
3
Neuroimaging study in autosomal dominant cerebellar ataxia, deafness, and narcolepsy. 56
10599806 1999
4
Cataplexy and ataxia: red flags for the diagnosis of DNA methyltransferase 1 mutation. 61
31957642 2020
5
Cataplexy and ataxia: red flags for the diagnosis of DNA methyltransferase 1 mutation. 61
31806079 2019

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

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

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DNMT1 NM_001130823.3(DNMT1):c.1816G>T (p.Val606Phe)SNV Pathogenic 50919 rs397509391 19:10265278-10265278 19:10154602-10154602
2 DNMT1 NM_001130823.3(DNMT1):c.1709C>T (p.Ala570Val)SNV Pathogenic 50920 rs397509392 19:10265385-10265385 19:10154709-10154709
3 DNMT1 NM_001130823.3(DNMT1):c.1814G>C (p.Gly605Ala)SNV Pathogenic 50921 rs397509393 19:10265280-10265280 19:10154604-10154604
4 DNMT1 NM_001130823.3(DNMT1):c.4298T>C (p.Met1433Thr)SNV Likely pathogenic 807592 19:10247952-10247952 19:10137276-10137276
5 DNMT1 NM_001130823.3(DNMT1):c.4636C>G (p.Pro1546Ala)SNV Uncertain significance 547912 rs1555687655 19:10246817-10246817 19:10136141-10136141
6 DNMT1 NM_001130823.3(DNMT1):c.650A>G (p.Asp217Gly)SNV Uncertain significance 634570 rs1568249130 19:10284580-10284580 19:10173904-10173904

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

73
# 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

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

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

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

# Name GO ID Score Top Affiliating Genes
1 nucleoplasm GO:0005654 9.76 ZBTB38 ZBTB33 ZBTB24 UHRF2 UHRF1 DNMT3B
2 heterochromatin GO:0000792 9.26 UHRF1 DNMT1
3 nuclear heterochromatin GO:0005720 8.96 UHRF2 UHRF1
4 replication fork GO:0005657 8.8 UHRF1 DNMT1 DMAP1

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

# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 9.8 ZBTB24 UHRF1 DNMT3B DNMT1 DMAP1
2 negative regulation of transcription, DNA-templated GO:0045892 9.77 ZBTB38 ZBTB33 DNMT3L DNMT1 DMAP1
3 negative regulation of gene expression, epigenetic GO:0045814 9.46 DNMT3B DNMT1
4 positive regulation of histone H3-K4 methylation GO:0051571 9.43 DNMT3B DNMT1
5 negative regulation of histone H3-K9 methylation GO:0051573 9.32 DNMT3B DNMT1
6 C-5 methylation of cytosine GO:0090116 9.26 DNMT3B DNMT1
7 DNA methylation on cytosine GO:0032776 9.16 DNMT3L DNMT1
8 maintenance of DNA methylation GO:0010216 9.13 UHRF2 UHRF1 DNMT1
9 DNA methylation GO:0006306 8.92 DNMT3L DNMT3B DNMT1 DMAP1

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 metal ion binding GO:0046872 9.92 ZBTB38 ZBTB33 ZBTB24 UHRF2 UHRF1 DNMT3L
2 DNA binding GO:0003677 9.8 ZBTB38 ZBTB33 ZBTB24 UHRF2 UHRF1 DNMT3B
3 DNA-methyltransferase activity GO:0009008 9.16 DNMT3B DNMT1
4 DNA (cytosine-5-)-methyltransferase activity GO:0003886 8.96 DNMT3B DNMT1
5 methyl-CpG binding GO:0008327 8.92 ZBTB38 ZBTB33 UHRF1 DNMT1

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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