MCID: LKD007
MIFTS: 39

Leukodystrophy, Adult-Onset, Autosomal Dominant

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

Aliases & Classifications for Leukodystrophy, Adult-Onset, Autosomal Dominant

MalaCards integrated aliases for Leukodystrophy, Adult-Onset, Autosomal Dominant:

Name: Leukodystrophy, Adult-Onset, Autosomal Dominant 54 24 29 13
Adld 12 24 56 71
Adult-Onset Autosomal Dominant Demyelinating Leukodystrophy 12 56 14
Adult-Onset Autosomal Dominant Leukodystrophy 12 56
Multiple Sclerosis-Like Disorder 24 71
Pelizaeus-Merzbacher Disease, Autosomal Dominant or Late-Onset Type 24
Autosomal-Dominant or Late-Onset Type Pelizaeus-Merzbacher Disease 12
Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant 69
Leukodystrophy, Demyelinating, Autosomal Dominant, Adult-Onset 71
Pelizaeus-Merzbacher Disease Autosomal Dominant 71
Adult Onset Autosomal Dominant Leukodystrophy 69
Pelizaeus-Merzbacher Disease Late-Onset Type 71

Characteristics:

Orphanet epidemiological data:

56
adult-onset autosomal dominant leukodystrophy
Inheritance: Autosomal dominant; Age of onset: Adult;

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
onset in the fourth to sixth decades (mean 40 years)
autonomic dysfunction usually precedes obvious neurologic deterioration
acute neurologic deterioration after viral illness has been reported
duplication of lmnb1 is sufficient for the disorder, although patients may also have larger duplications
one family with a deletion upstream of the lmnb1 gene did not have autonomic symptoms or cerebellar involvement


HPO:

32
leukodystrophy, adult-onset, autosomal dominant:
Onset and clinical course adult onset progressive
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Leukodystrophy, Adult-Onset, Autosomal Dominant

OMIM : 54
Autosomal dominant adult-onset demyelinating leukodystrophy is a slowly progressive and fatal disorder that presents in the fourth or fifth decade of life and is characterized clinically by early autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS. ADLD differs from multiple sclerosis and other demyelinating disorders in that neuropathology shows preservation of oligodendroglia in the presence of subtotal demyelination and lack of astrogliosis (summary by Padiath et al., 2006). Characteristic MRI findings include T2-weighted hyperintense changes in the upper corticospinal tract and cerebellar peduncles, with later development of confluent white matter changes in the frontoparietal area with relative sparing of the periventricular white matter (summary by Schuster et al., 2011). (169500)

MalaCards based summary : Leukodystrophy, Adult-Onset, Autosomal Dominant, also known as adld, is related to autosomal dominant leukodystrophy with autonomic disease and reynolds syndrome, and has symptoms including nystagmus, dysphagia and dysarthria. An important gene associated with Leukodystrophy, Adult-Onset, Autosomal Dominant is LMNB1 (Lamin B1), and among its related pathways/superpathways are Apoptotic cleavage of cellular proteins and Granzyme Pathway. Affiliated tissues include spinal cord, eye and parietal lobe, and related phenotype is Increased shRNA abundance (Z-score > 2).

Disease Ontology : 12 A leukodystrophy characterized by onset in the 4th or 5th decade of life of autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS that has material basis in heterozygous tandem genomic duplication resulting in an extra copy of the LMNB1 gene on chromosome 5q.

UniProtKB/Swiss-Prot : 71 Leukodystrophy, demyelinating, autosomal dominant, adult-onset: A slowly progressive and fatal demyelinating leukodystrophy, presenting in the fourth or fifth decade of life. Clinically characterized by early autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS. It differs from multiple sclerosis and other demyelinating disorders in that neuropathology shows preservation of oligodendroglia in the presence of subtotal demyelination and lack of astrogliosis.

Related Diseases for Leukodystrophy, Adult-Onset, Autosomal Dominant

Diseases in the Leukodystrophy family:

Leukodystrophy, Adult-Onset, Autosomal Dominant Tubb4a-Related Leukodystrophy

Diseases related to Leukodystrophy, Adult-Onset, Autosomal Dominant via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 autosomal dominant leukodystrophy with autonomic disease 11.6
2 reynolds syndrome 10.0 LMNA LMNB1
3 pelger-huet anomaly 10.0 LMNA LMNB1
4 leukodystrophy 10.0
5 hutchinson-gilford progeria 9.8 LMNA LMNB1
6 sclerosing keratitis 9.6 HTRA1 LMNB1
7 parametrium malignant neoplasm 9.6 LMNA LMNB1
8 amelogenesis imperfecta 9.5 HTRA1 LMNA
9 myopathy, areflexia, respiratory distress, and dysphagia, early-onset 7.6 APOPT1 CTC1 HTRA1 LMNA LMNB1 MARCH3

Graphical network of the top 20 diseases related to Leukodystrophy, Adult-Onset, Autosomal Dominant:



Diseases related to Leukodystrophy, Adult-Onset, Autosomal Dominant

Symptoms & Phenotypes for Leukodystrophy, Adult-Onset, Autosomal Dominant

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Eyes:
nystagmus

Neurologic- Behavioral Psychiatric Manifestations:
personality changes
depression

Abdomen- Gastroin testinal:
abnormal bowel regulation due to autonomic dysfunction

Genitourinary- Bladder:
abnormal bladder regulation due to autonomic dysfunction

Laboratory- Abnormalities:
patient cells have increased levels of lmnb1 mrna and protein

Neurologic- Central Nervous System:
hyperreflexia
spasticity
extensor plantar responses
pyramidal signs
cerebellar ataxia
more
Cardiovascular- Vascular:
orthostatic hypotension due to autonomic dysfunction

Genitourinary- External Genitalia Male:
impotence due to autonomic dysfunction

Skin Nails & Hair- Skin:
decreased sweating due to autonomic dysfunction


Clinical features from OMIM:

169500

Human phenotypes related to Leukodystrophy, Adult-Onset, Autosomal Dominant:

56 32 (show all 39)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 56 32 frequent (33%) Frequent (79-30%) HP:0000639
2 dysphagia 56 32 occasional (7.5%) Occasional (29-5%) HP:0002015
3 dysarthria 56 32 occasional (7.5%) Occasional (29-5%) HP:0001260
4 ataxia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001251
5 tremor 56 32 frequent (33%) Frequent (79-30%) HP:0001337
6 hyperreflexia 56 32 frequent (33%) Frequent (79-30%) HP:0001347
7 spasticity 56 32 frequent (33%) Frequent (79-30%) HP:0001257
8 global developmental delay 56 32 occasional (7.5%) Occasional (29-5%) HP:0001263
9 urinary urgency 56 32 frequent (33%) Frequent (79-30%) HP:0000012
10 cerebral cortical atrophy 56 32 occasional (7.5%) Occasional (29-5%) HP:0002120
11 intellectual disability, mild 56 32 occasional (7.5%) Occasional (29-5%) HP:0001256
12 constipation 56 32 frequent (33%) Frequent (79-30%) HP:0002019
13 tetraparesis 56 32 frequent (33%) Frequent (79-30%) HP:0002273
14 hypohidrosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0000966
15 impotence 56 32 frequent (33%) Frequent (79-30%) HP:0000802
16 hypotension 56 32 frequent (33%) Frequent (79-30%) HP:0002615
17 gait disturbance 56 32 frequent (33%) Frequent (79-30%) HP:0001288
18 visual loss 56 32 occasional (7.5%) Occasional (29-5%) HP:0000572
19 hearing impairment 56 32 occasional (7.5%) Occasional (29-5%) HP:0000365
20 corpus callosum atrophy 56 32 occasional (7.5%) Occasional (29-5%) HP:0007371
21 abnormal pyramidal signs 56 32 frequent (33%) Frequent (79-30%) HP:0007256
22 atrophy of the spinal cord 56 32 occasional (7.5%) Occasional (29-5%) HP:0006827
23 dilatation of the bladder 56 32 frequent (33%) Frequent (79-30%) HP:0010955
24 personality changes 32 HP:0000751
25 depression 32 HP:0000716
26 progressive neurologic deterioration 32 HP:0002344
27 leukodystrophy 32 HP:0002415
28 gliosis 32 HP:0002171
29 pseudobulbar paralysis 32 HP:0007024
30 babinski sign 32 HP:0003487
31 dysautonomia 32 HP:0002459
32 orthostatic hypotension due to autonomic dysfunction 32 HP:0004926
33 decreased sweating due to autonomic dysfunction 32 HP:0007480
34 abnormality of the urinary system 32 HP:0000079
35 autonomic bladder dysfunction 32 HP:0005341
36 peripheral demyelination 32 HP:0011096
37 diffuse leukoencephalopathy 32 HP:0006994
38 symmetric peripheral demyelination 32 HP:0007262
39 autonomic erectile dysfunction 32 HP:0008652

UMLS symptoms related to Leukodystrophy, Adult-Onset, Autosomal Dominant:


cerebellar ataxia, muscle spasticity, abnormal pyramidal signs, personality changes

GenomeRNAi Phenotypes related to Leukodystrophy, Adult-Onset, Autosomal Dominant according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-131 9.23 LMNA LMNB1
2 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.23 LMNA
3 Increased shRNA abundance (Z-score > 2) GR00366-A-201 9.23 LMNB1
4 Increased shRNA abundance (Z-score > 2) GR00366-A-208 9.23 LMNB1
5 Increased shRNA abundance (Z-score > 2) GR00366-A-81 9.23 LMNB1
6 Increased shRNA abundance (Z-score > 2) GR00366-A-88 9.23 LMNB1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-90 9.23 LMNA

Drugs & Therapeutics for Leukodystrophy, Adult-Onset, Autosomal Dominant

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Leukodystrophy, Adult-Onset, Autosomal Dominant

Genetic Tests for Leukodystrophy, Adult-Onset, Autosomal Dominant

Genetic tests related to Leukodystrophy, Adult-Onset, Autosomal Dominant:

id Genetic test Affiliating Genes
1 Leukodystrophy, Adult-Onset, Autosomal Dominant 29 24 LMNB1

Anatomical Context for Leukodystrophy, Adult-Onset, Autosomal Dominant

MalaCards organs/tissues related to Leukodystrophy, Adult-Onset, Autosomal Dominant:

39
Spinal Cord, Eye, Parietal Lobe

Publications for Leukodystrophy, Adult-Onset, Autosomal Dominant

Variations for Leukodystrophy, Adult-Onset, Autosomal Dominant

ClinVar genetic disease variations for Leukodystrophy, Adult-Onset, Autosomal Dominant:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 LMNB1 LMNB1, DUP, CHR5: 126,102,443-126,199,753 SRO, GRCh37 duplication Pathogenic

Expression for Leukodystrophy, Adult-Onset, Autosomal Dominant

Search GEO for disease gene expression data for Leukodystrophy, Adult-Onset, Autosomal Dominant.

Pathways for Leukodystrophy, Adult-Onset, Autosomal Dominant

Pathways related to Leukodystrophy, Adult-Onset, Autosomal Dominant according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
11.32 LMNA LMNB1
2
Show member pathways
10.84 LMNA LMNB1
3
Show member pathways
10.62 LMNA LMNB1
4
Show member pathways
10.14 LMNA LMNB1

GO Terms for Leukodystrophy, Adult-Onset, Autosomal Dominant

Cellular components related to Leukodystrophy, Adult-Onset, Autosomal Dominant according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 nuclear envelope GO:0005635 8.96 LMNA LMNB1
2 lamin filament GO:0005638 8.62 LMNA LMNB1

Sources for Leukodystrophy, Adult-Onset, Autosomal Dominant

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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