ADCADN
MCID: CRB142
MIFTS: 44

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
Autosomal Dominant Cerebellar Ataxia-Hearing Loss-Narcolepsy Syndrome 58
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 One carbon pool by folate and Sulfur amino acid metabolism. 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

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

(show all 35)
# Related Disease Score Top Affiliating Genes
1 neuropathy, hereditary sensory, type ie 29.1 UHRF1 DNMT3L DNMT3A DNMT1 DMAP1
2 ataxia and polyneuropathy, adult-onset 10.7
3 branchiootic syndrome 1 10.7
4 autosomal dominant cerebellar ataxia 10.7
5 sensory peripheral neuropathy 10.4
6 optic nerve disease 10.4
7 dentatorubral-pallidoluysian atrophy 10.3
8 spinocerebellar ataxia 1 10.3
9 3-methylglutaconic aciduria, type iii 10.3
10 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.3
11 hereditary sensory neuropathy 10.3
12 autonomic neuropathy 10.3
13 hypertrophic cardiomyopathy 10.3
14 polyneuropathy 10.3
15 neuropathy 10.3
16 narcolepsy 10.3
17 dnmt1-related disorder 10.3
18 immunodeficiency-centromeric instability-facial anomalies syndrome 1 10.1 DNMT3B DNMT1
19 mutagen sensitivity 10.1 DNMT3B DNMT1
20 immunodeficiency-centromeric instability-facial anomalies syndrome 2 10.1 ZBTB24 DNMT3B
21 hereditary sensory and autonomic neuropathy type 1 10.0 NAA50 DNMT1
22 oligospermia 9.8 UHRF1 DNMT1
23 lymphosarcoma 9.8 DNMT3A DNMT1
24 rahman syndrome 9.7 H1-4 DNMT3A
25 retinitis pigmentosa 58 9.7 DNMT3A DMAP1
26 adult syndrome 9.6 DNMT3B DNMT3A DNMT1
27 hyperoxaluria, primary, type i 9.6 DNMT3B DNMT3A DNMT1
28 primary hyperoxaluria 9.6 DNMT3B DNMT3A DNMT1
29 testicular spermatocytic seminoma 9.5 DNMT3L DNMT3B DNMT3A
30 alpha thalassemia-x-linked intellectual disability syndrome 9.5 DNMT3L DNMT3B DNMT3A
31 sotos syndrome 1 9.4 DNMT3L DNMT3B DNMT3A
32 weaver syndrome 9.3 H1-4 DNMT3L DNMT3A
33 beckwith-wiedemann syndrome 9.2 DNMT3L DNMT3B DNMT3A DNMT1
34 cartilage-hair hypoplasia 9.1 UHRF1 DNMT3L DNMT3B DNMT3A DNMT1
35 immunodeficiency-centromeric instability-facial anomalies syndrome 8.3 ZBTB38 ZBTB24 UHRF1 DNMT3L DNMT3B DNMT3A

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 cataract 58 31 occasional (7.5%) Occasional (29-5%) HP:0000518
6 spasticity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001257
7 sensory neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000763
8 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
9 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
10 hyperreflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001347
11 memory impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0002354
12 depressivity 58 31 occasional (7.5%) Occasional (29-5%) HP:0000716
13 mental deterioration 58 31 occasional (7.5%) Occasional (29-5%) HP:0001268
14 babinski sign 58 31 occasional (7.5%) Occasional (29-5%) HP:0003487
15 cerebellar atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001272
16 head tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0002346
17 cerebral atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002059
18 abnormality of the cerebral white matter 58 31 occasional (7.5%) Occasional (29-5%) HP:0002500
19 urinary incontinence 58 31 occasional (7.5%) Occasional (29-5%) HP:0000020
20 atrophy/degeneration affecting the brainstem 58 31 occasional (7.5%) Occasional (29-5%) HP:0007366
21 predominantly lower limb lymphedema 58 31 occasional (7.5%) Occasional (29-5%) HP:0003550
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 primitive reflex 58 31 occasional (7.5%) Occasional (29-5%) HP:0002476
26 abnormality of the cerebrospinal fluid 58 31 occasional (7.5%) Occasional (29-5%) HP:0002921
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 cataplexy 31 HP:0002524
32 excessive daytime sleepiness 31 HP:0002189

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
spasticity
hyperreflexia
cerebellar atrophy
dementia
narcolepsy
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

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 9.7 DMAP1 DNMT1 DNMT3A DNMT3B DNMT3L MBD2
2 reproductive system MP:0005389 9.17 DMAP1 DNMT1 DNMT3A DNMT3B DNMT3L MBD2

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

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. 6 56
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 nucleus GO:0005634 10.03 ZBTB38 ZBTB24 UHRF2 UHRF1 NAA50 MBD2
2 nucleoplasm GO:0005654 10.02 ZBTB38 ZBTB24 UHRF2 UHRF1 MBD2 DNMT3B
3 replication fork GO:0005657 9.33 UHRF1 DNMT1 DMAP1
4 euchromatin GO:0000791 9.32 UHRF1 DNMT3A
5 heterochromatin GO:0000792 9.26 UHRF1 MBD2 DNMT3A DNMT1
6 nuclear heterochromatin GO:0005720 8.92 UHRF2 UHRF1 H1-4 DNMT3A

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

(show all 20)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 9.86 ZBTB24 UHRF1 MBD2 H1-4 DNMT3B DNMT3A
2 negative regulation of transcription, DNA-templated GO:0045892 9.85 ZBTB38 MBD2 DNMT3L DNMT1 DMAP1
3 chromatin organization GO:0006325 9.81 UHRF1 DNMT3A DNMT1 DMAP1
4 methylation GO:0032259 9.74 DNMT3B DNMT3A DNMT1
5 response to estradiol GO:0032355 9.67 MBD2 DNMT3B DNMT3A
6 response to ionizing radiation GO:0010212 9.59 DNMT3B DNMT3A
7 response to cocaine GO:0042220 9.58 DNMT3B DNMT3A
8 histone H4 acetylation GO:0043967 9.58 NAA50 DMAP1
9 response to vitamin A GO:0033189 9.56 DNMT3B DNMT3A
10 DNA methylation involved in gamete generation GO:0043046 9.55 DNMT3L DNMT3A
11 positive regulation of histone H3-K4 methylation GO:0051571 9.54 DNMT3B DNMT1
12 negative regulation of gene expression, epigenetic GO:0045814 9.54 DNMT3B DNMT3A DNMT1
13 regulation of gene expression by genetic imprinting GO:0006349 9.52 DNMT3L DNMT3A
14 maintenance of DNA methylation GO:0010216 9.5 UHRF2 UHRF1 DNMT1
15 methylation-dependent chromatin silencing GO:0006346 9.48 MBD2 DNMT3A
16 negative regulation of histone H3-K9 methylation GO:0051573 9.43 DNMT3B DNMT1
17 DNA methylation involved in embryo development GO:0043045 9.4 DNMT3A DNMT1
18 C-5 methylation of cytosine GO:0090116 9.33 DNMT3B DNMT3A DNMT1
19 DNA methylation on cytosine GO:0032776 9.13 DNMT3L DNMT3A DNMT1
20 DNA methylation GO:0006306 9.02 DNMT3L DNMT3B DNMT3A DNMT1 DMAP1

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

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.13 ZBTB38 ZBTB24 UHRF2 UHRF1 RTN4IP1 NAA50
2 metal ion binding GO:0046872 10.03 ZBTB38 ZBTB24 UHRF2 UHRF1 DNMT3L DNMT3B
3 transferase activity GO:0016740 9.93 UHRF2 UHRF1 NAA50 DNMT3B DNMT3A DNMT1
4 DNA binding GO:0003677 9.91 ZBTB38 ZBTB24 UHRF2 UHRF1 MBD2 H1-4
5 transcription corepressor activity GO:0003714 9.67 DNMT3B DNMT3A DMAP1
6 chromatin binding GO:0003682 9.67 MBD2 DNMT3B DNMT3A DNMT1
7 methyltransferase activity GO:0008168 9.58 DNMT3B DNMT3A DNMT1
8 nucleosomal DNA binding GO:0031492 9.48 MBD2 H1-4
9 methyl-CpG binding GO:0008327 9.46 ZBTB38 UHRF1 MBD2 DNMT1
10 DNA-methyltransferase activity GO:0009008 9.13 DNMT3B DNMT3A DNMT1
11 DNA (cytosine-5-)-methyltransferase activity GO:0003886 8.8 DNMT3B DNMT3A 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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