MCID: LKD025
MIFTS: 42

Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

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

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

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

Name: Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant 57 73
Leukodystrophy, Adult-Onset, Autosomal Dominant 57 29 13 6 40
Adld 57 12 59 75
Adult-Onset Autosomal Dominant Demyelinating Leukodystrophy 12 59 15
Adult-Onset Autosomal Dominant Leukodystrophy 12 59 37
Pelizaeus-Merzbacher Disease, Autosomal Dominant or Late-Onset Type, Formerly 57
Autosomal-Dominant or Late-Onset Type Pelizaeus-Merzbacher Disease 12
Leukodystrophy, Demyelinating, Autosomal Dominant, Adult-Onset 75
Pelizaeus-Merzbacher Disease Autosomal Dominant 75
Adult Onset Autosomal Dominant Leukodystrophy 73
Pelizaeus-Merzbacher Disease Late-Onset Type 75
Multiple Sclerosis-Like Disorder 75

Characteristics:

Orphanet epidemiological data:

59
adult-onset autosomal dominant leukodystrophy
Inheritance: Autosomal dominant; Age of onset: Adult;

OMIM:

57
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, demyelinating, adult-onset, autosomal dominant:
Onset and clinical course adult onset progressive
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

OMIM : 57 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, Demyelinating, Adult-Onset, Autosomal Dominant, also known as leukodystrophy, adult-onset, autosomal dominant, is related to autosomal dominant leukodystrophy with autonomic disease and reynolds syndrome, and has symptoms including cerebellar ataxia, muscle spasticity and abnormal pyramidal signs. An important gene associated with Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant is LMNB1 (Lamin B1), and among its related pathways/superpathways are Apoptosis and Autophagy and Apoptosis and survival Caspase cascade. Affiliated tissues include spinal cord, eye and parietal lobe, and related phenotypes are nystagmus and ataxia

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 : 75 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, Demyelinating, Adult-Onset, Autosomal Dominant

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

# Related Disease Score Top Affiliating Genes
1 autosomal dominant leukodystrophy with autonomic disease 11.5
2 reynolds syndrome 10.0 LMNA LMNB1
3 pelger-huet anomaly 10.0 LMNA LMNB1
4 partial lipodystrophy 9.9 LMNA LMNB1
5 emery-dreifuss muscular dystrophy 9.7 LMNA LMNB1
6 cerebral degeneration 9.5 HTRA1 LMNB1
7 hutchinson-gilford progeria syndrome 9.5 LMNA LMNB1

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



Diseases related to Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

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

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus

Cardiovascular Vascular:
orthostatic hypotension due to autonomic dysfunction

Abdomen Gastrointestinal:
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:
spasticity
hyperreflexia
autonomic dysfunction
pyramidal signs
extensor plantar responses
more
Neurologic Behavioral Psychiatric Manifestations:
personality changes
depression

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, Demyelinating, Adult-Onset, Autosomal Dominant:

59 32 (show all 39)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 59 32 frequent (33%) Frequent (79-30%) HP:0000639
2 ataxia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001251
3 spasticity 59 32 frequent (33%) Frequent (79-30%) HP:0001257
4 dysarthria 59 32 occasional (7.5%) Occasional (29-5%) HP:0001260
5 gait disturbance 59 32 frequent (33%) Frequent (79-30%) HP:0001288
6 tremor 59 32 frequent (33%) Frequent (79-30%) HP:0001337
7 hyperreflexia 59 32 frequent (33%) Frequent (79-30%) HP:0001347
8 dysphagia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002015
9 constipation 59 32 frequent (33%) Frequent (79-30%) HP:0002019
10 hypotension 59 32 frequent (33%) Frequent (79-30%) HP:0002615
11 abnormal pyramidal signs 59 32 frequent (33%) Frequent (79-30%) HP:0007256
12 hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000365
13 global developmental delay 59 32 occasional (7.5%) Occasional (29-5%) HP:0001263
14 intellectual disability, mild 59 32 occasional (7.5%) Occasional (29-5%) HP:0001256
15 hypohidrosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000966
16 cerebral cortical atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0002120
17 visual loss 59 32 occasional (7.5%) Occasional (29-5%) HP:0000572
18 corpus callosum atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0007371
19 impotence 59 32 frequent (33%) Frequent (79-30%) HP:0000802
20 tetraparesis 59 32 frequent (33%) Frequent (79-30%) HP:0002273
21 atrophy of the spinal cord 59 32 occasional (7.5%) Occasional (29-5%) HP:0006827
22 urinary urgency 59 32 frequent (33%) Frequent (79-30%) HP:0000012
23 dilatation of the bladder 59 32 frequent (33%) Frequent (79-30%) HP:0010955
24 depressivity 32 HP:0000716
25 dysautonomia 32 HP:0002459
26 babinski sign 32 HP:0003487
27 abnormality of the urinary system 32 HP:0000079
28 peripheral demyelination 32 HP:0011096
29 leukodystrophy 32 HP:0002415
30 orthostatic hypotension due to autonomic dysfunction 32 HP:0004926
31 personality changes 32 HP:0000751
32 gliosis 32 HP:0002171
33 progressive neurologic deterioration 32 HP:0002344
34 pseudobulbar paralysis 32 HP:0007024
35 autonomic bladder dysfunction 32 HP:0005341
36 autonomic erectile dysfunction 32 HP:0008652
37 decreased sweating due to autonomic dysfunction 32 HP:0007480
38 diffuse leukoencephalopathy 32 HP:0006994
39 symmetric peripheral demyelination 32 HP:0007262

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


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

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

26
# 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, Demyelinating, Adult-Onset, Autosomal Dominant

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

Genetic Tests for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

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

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

Anatomical Context for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

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

41
Spinal Cord, Eye, Parietal Lobe, Brain

Publications for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

Articles related to Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant:

(show all 15)
# Title Authors Year
1
An LMNB1 Duplication Caused Adult-Onset Autosomal Dominant Leukodystrophy in Chinese Family: Clinical Manifestations, Neuroradiology and Genetic Diagnosis. ( 28769756 )
2017
2
A longitudinal study of a family with adult-onset autosomal dominant leukodystrophy: Clinical, autonomic and neuropsychological findings. ( 26896090 )
2016
3
Brain magnetic resonance metabolic and microstructural changes in adult-onset autosomal dominant leukodystrophy. ( 26189928 )
2015
4
Adult-onset autosomal dominant leukodystrophy presenting with REM sleep behavior disorder. ( 23243074 )
2013
5
Adult-onset autosomal dominant leukodystrophy without early autonomic dysfunctions linked to lamin B1 duplication: a phenotypic variant. ( 23681646 )
2013
6
Oct-1 recruitment to the nuclear envelope in adult-onset autosomal dominant leukodystrophy. ( 23261988 )
2013
7
A^H-MR spectroscopy of adult-onset autosomal dominant leukodystrophy with autonomic symptoms. ( 23636437 )
2013
8
Adult-onset autosomal dominant leukodystrophy due to LMNB1 gene duplication. ( 21909802 )
2012
9
Adult-onset autosomal dominant leukodystrophy: linking nuclear envelope to myelin. ( 21273400 )
2011
10
Isolated noradrenergic failure in adult-onset autosomal dominant leukodystrophy. ( 20719577 )
2011
11
Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms. ( 21225301 )
2011
12
N-CAM dysfunction and unexpected accumulation of PSA-NCAM in brain of adult-onset autosomal-dominant leukodystrophy. ( 19725832 )
2010
13
MR imaging characteristics and neuropathology of the spinal cord in adult-onset autosomal dominant leukodystrophy with autonomic symptoms. ( 18945794 )
2009
14
MR characteristics and neuropathology in adult-onset autosomal dominant leukodystrophy with autonomic symptoms. ( 16611789 )
2006
15
Adult-onset autosomal dominant leukodystrophy with autonomic symptoms restricted to 1.5 Mbp on chromosome 5q23. ( 16823806 )
2006

Variations for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

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

6
# 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, Demyelinating, Adult-Onset, Autosomal Dominant

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

Pathways for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

GO Terms for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

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

# Name GO ID Score Top Affiliating Genes
1 intermediate filament GO:0005882 9.16 LMNA LMNB1
2 nuclear envelope GO:0005635 8.96 LMNA LMNB1
3 lamin filament GO:0005638 8.62 LMNA LMNB1

Sources for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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