Autosomal Dominant Leukodystrophy with Autonomic Disease (ADLD)

Categories: Mental diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Autosomal Dominant Leukodystrophy with Autonomic Disease

MalaCards integrated aliases for Autosomal Dominant Leukodystrophy with Autonomic Disease:

Name: Autosomal Dominant Leukodystrophy with Autonomic Disease 25 20 43
Autosomal Dominant Adult-Onset Demyelinating Leukodystrophy 25 20 43
Adld 25 20 43
Adult-Onset Autosomal Dominant Leukodystrophy with Autonomic Symptoms 25 43
Pelizaeus-Merzbacher Disease, Autosomal Dominant or Late-Onset Type 20 6
Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant 20 71
Lmnb1-Related Adult-Onset Autosomal Dominant Leukodystrophy 25 43
Adult-Onset Autosomal Dominant Demyelinating Leukodystrophy 20
Adult-Onset Autosomal Dominant Leukodystrophy 20
Adult Onset Autosomal Dominant Leukodystrophy 71
Multiple Sclerosis-Like Disorder 20



Penetrance The disease presents in the fourth to fifth decades of adulthood with no gender variation. penetrance is not known but is thought to be 100%.


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UMLS 71 C1868512 C3164344

Summaries for Autosomal Dominant Leukodystrophy with Autonomic Disease

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 99027DefinitionA rare, slowly progressive neurological disorder involving centralnervous systemdemyelination, leading to autonomic dysfunction, ataxia and mild cognitive impairment.EpidemiologyMore than 20 families in different ethnic groups have been reported to date. Exact prevalence and incidence data are however lacking.Clinical descriptionUnlike mostforms of leukodystrophy which appear in childhood, ADLD occurs in the 4th to 6th decade of life. ADLD may clinically resemble multiple sclerosis in the initial phase. In most patients, the initial manifestation of the disease is autonomic dysfunction resulting in micturitionurgency, bladder retention, constipation, postural hypotensionanderectile dysfunction in affected males. Decreased sweating is reported in some cases. Some patients develop autonomic dysfunction later in the disease course. The other features are cerebellardysfunction (gait ataxia, nystagmus, dysmetria, loss of fine motor control, and action tremors), pyramidal signs (spasticity, weakness of both upper and lower extremities, hyperreflexia), and cognitive impairment possibly with personality changes. These manifestations may not develop for years following initial presentation. Neuroradiologicalcharacteristics include extensive symmetrical white matter changes, corpus callosum atrophy, and brain stem and spinal cord atrophy. The disease follows a slow progressive course with an eventual loss of walking ability and slightly shortened lifespan.EtiologyADLD is caused by chromosomal rearrangements with duplications of the LMNB1 gene (5q23.2) or a ''position effect'' due to a genomic deletion upstream of the gene causing its upregulation. Overexpression of LMNB1 causes myelin disruptionin the central nervous system for which the precise underlying pathogenic mechanisms have not been elucidated. Alteration of splicing patterns suggests that ADLD is a spliceopathy.Genetic counselingGenetic counseling should be provided to affected families indicating the autosomal dominant pattern of inheritance.Visit the Orphanet disease page for more resources.

MalaCards based summary : Autosomal Dominant Leukodystrophy with Autonomic Disease, also known as autosomal dominant adult-onset demyelinating leukodystrophy, is related to leukodystrophy, demyelinating, adult-onset, autosomal dominant and ataxia and polyneuropathy, adult-onset, and has symptoms including personality changes, muscle spasticity and cerebellar ataxia. An important gene associated with Autosomal Dominant Leukodystrophy with Autonomic Disease is LMNB1 (Lamin B1). Affiliated tissues include spinal cord and medulla oblongata.

MedlinePlus Genetics : 43 Autosomal dominant leukodystrophy with autonomic disease (ADLD) is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are characterized by abnormalities of the nervous system's white matter, which consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates and protects nerve fibers and promotes the rapid transmission of nerve impulses.People with ADLD develop signs and symptoms of the condition in adulthood, typically in their forties or fifties. The first signs of the condition often involve problems with the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. These problems include difficulty with bowel and bladder function, a sharp drop in blood pressure upon standing (orthostatic hypotension), and erectile dysfunction in men. Rarely, people experience an inability to sweat (anhidrosis), which can lead to a dangerously high body temperature.In ADLD, movement difficulties often develop after the autonomic nervous system problems. Affected individuals can have muscle stiffness (spasticity) or weakness and involuntary rhythmic shaking, called intention tremor because it worsens during movement. People with ADLD often have difficulty coordinating movements (ataxia), including movements that involve judging distance or scale (dysmetria), such as picking up a distant object, and rapidly alternating movements (dysdiadochokinesis), including hand clapping or foot stomping. These movement problems usually first affect the legs, but as the condition worsens, the arms and eventually the face become involved. In some people with ADLD, the symptoms worsen during episodes of fever, infection, or exposure to heat. Due to difficulty walking and an unsteady gait, many affected individuals need a cane, walker, or wheelchair for assistance.Intelligence is usually unaffected; however, people who have had ADLD for a long time may have a decline in intellectual function (dementia). ADLD worsens slowly, and affected individuals usually survive 10 to 20 years after the onset of symptoms.

GeneReviews: NBK338165

Related Diseases for Autosomal Dominant Leukodystrophy with Autonomic Disease

Graphical network of the top 20 diseases related to Autosomal Dominant Leukodystrophy with Autonomic Disease:

Diseases related to Autosomal Dominant Leukodystrophy with Autonomic Disease

Symptoms & Phenotypes for Autosomal Dominant Leukodystrophy with Autonomic Disease

UMLS symptoms related to Autosomal Dominant Leukodystrophy with Autonomic Disease:

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

Drugs & Therapeutics for Autosomal Dominant Leukodystrophy with Autonomic Disease

Search Clinical Trials , NIH Clinical Center for Autosomal Dominant Leukodystrophy with Autonomic Disease

Genetic Tests for Autosomal Dominant Leukodystrophy with Autonomic Disease

Anatomical Context for Autosomal Dominant Leukodystrophy with Autonomic Disease

MalaCards organs/tissues related to Autosomal Dominant Leukodystrophy with Autonomic Disease:

Spinal Cord, Medulla Oblongata

Publications for Autosomal Dominant Leukodystrophy with Autonomic Disease

Articles related to Autosomal Dominant Leukodystrophy with Autonomic Disease:

(show all 48)
# Title Authors PMID Year
Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression. 6 25
23649844 2013
Adult-onset autosomal dominant leukodystrophy due to LMNB1 gene duplication. 6 25
21909802 2012
Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms. 25 6
21225301 2011
A novel family with Lamin B1 duplication associated with adult-onset leucoencephalopathy. 25 6
19151023 2009
Lamin B1 duplications cause autosomal dominant leukodystrophy. 6 25
16951681 2006
A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD). 61 25
25701871 2015
LMNB1-related autosomal-dominant leukodystrophy: Clinical and radiological course. 25
26053668 2015
Defects of Lipid Synthesis Are Linked to the Age-Dependent Demyelination Caused by Lamin B1 Overexpression. 25
26311780 2015
Messenger RNA processing is altered in autosomal dominant leukodystrophy. 25
25637521 2015
Consensus statement on preventive and symptomatic care of leukodystrophy patients. 25
25577286 2015
Metachromatic leukodystrophy: Disease spectrum and approaches for treatment. 25
25987178 2015
Vitamin B12 deficiency: an important reversible co-morbidity in neuropsychiatric manifestations. 25
25722508 2015
Lamin B1 overexpression increases nuclear rigidity in autosomal dominant leukodystrophy fibroblasts. 25
24858279 2014
Guidelines for the diagnosis and treatment of cobalamin and folate disorders. 25
24942828 2014
A practical approach to diagnosing adult onset leukodystrophies. 25
24357685 2014
Patterns of magnetic resonance imaging abnormalities in symptomatic patients with Krabbe disease correspond to phenotype. 25
24262341 2014
Nuclear envelope: connecting structural genome organization to regulation of gene expression. 25
24563350 2014
Adult-onset autosomal dominant leukodystrophy without early autonomic dysfunctions linked to lamin B1 duplication: a phenotypic variant. 25
23681646 2013
Lamin B1 mediates cell-autonomous neuropathology in a leukodystrophy mouse model. 25
23676464 2013
Oct-1 recruitment to the nuclear envelope in adult-onset autosomal dominant leukodystrophy. 25
23261988 2013
Nuclear lamins in the brain - new insights into function and regulation. 25
23065386 2013
Nuclear lamin functions and disease. 25
22795640 2012
Magnetic resonance imaging findings within the posterior and lateral columns of the spinal cord extended from the medulla oblongata to the thoracic spine in a woman with subacute combined degeneration without hematologic disorders: a case report and review of the literature. 25
21524288 2011
Isolated noradrenergic failure in adult-onset autosomal dominant leukodystrophy. 25
20719577 2011
A family with autosomal dominant leukodystrophy linked to 5q23.2-q23.3 without lamin B1 mutations. 25
19961535 2010
Autosomal dominant leukodystrophy caused by lamin B1 duplications a clinical and molecular case study of altered nuclear function and disease. 25
20816241 2010
MR imaging characteristics and neuropathology of the spinal cord in adult-onset autosomal dominant leukodystrophy with autonomic symptoms. 25
18945794 2009
A novel duplication confirms the involvement of 5q23.2 in autosomal dominant leukodystrophy. 25
19001169 2008
The earliest MR imaging and proton MR spectroscopy abnormalities in adult-onset Krabbe disease. 25
17824908 2007
Adult-onset autosomal dominant leukodystrophy with autonomic symptoms restricted to 1.5 Mbp on chromosome 5q23. 25
16823806 2006
MR characteristics and neuropathology in adult-onset autosomal dominant leukodystrophy with autonomic symptoms. 25
16611789 2006
MR imaging and proton MR spectroscopy in adult Krabbe disease. 25
11003282 2000
Multiple sclerosis. 25
11006371 2000
MRI and CT in an autosomal-dominant, adult-onset leukodystrophy. 25
9225322 1997
Autosomal dominant late-onset leukoencephalopathy. Clinical report of a new Italian family. 25
9018034 1997
Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization. 25
8838815 1996
Genomic structure of the mouse gene (Lmnb1) encoding nuclear lamin B1. 25
8586436 1995
Structural organization of the human gene (LMNB1) encoding nuclear lamin B1. 25
7557986 1995
Clinical and pathological features of an autosomal dominant, adult-onset leukodystrophy simulating chronic progressive multiple sclerosis. 25
8042923 1994
Computed tomography and magnetic resonance imaging in adult-onset leukodystrophy. 25
3415518 1988
Hereditary adult-onset leukodystrophy simulating chronic progressive multiple sclerosis. 25
6472420 1984
New diagnostic criteria for multiple sclerosis: guidelines for research protocols. 25
6847134 1983
Adult polyglucosan body disease-an atypical compound heterozygous with a novel GBE1 mutation. 61
33517539 2021
Allele-specific silencing as treatment for gene duplication disorders: proof-of-principle in autosomal dominant leukodystrophy. 61
31143934 2019
Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy. 61
30697589 2018
Adulthood leukodystrophies. 61
29302065 2018
An LMNB1 Duplication Caused Adult-Onset Autosomal Dominant Leukodystrophy in Chinese Family: Clinical Manifestations, Neuroradiology and Genetic Diagnosis. 61
28769756 2017
Autosomal Dominant Leukodystrophy with Autonomic Disease 61
26749591 2016

Variations for Autosomal Dominant Leukodystrophy with Autonomic Disease

ClinVar genetic disease variations for Autosomal Dominant Leukodystrophy with Autonomic Disease:

6 (show all 45)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 LMNB1 LMNB1, DUP, CHR5:126,102,443-126,199,753 SRO, GRCh37 Duplication Pathogenic 14476
2 LMNB1 NM_005573.4(LMNB1):c.676C>T (p.Arg226Cys) SNV Conflicting interpretations of pathogenicity 350615 rs142016804 5:126145905-126145905 5:126810213-126810213
3 LMNB1 NM_005573.4(LMNB1):c.*54A>T SNV Uncertain significance 905851 5:126172010-126172010 5:126836318-126836318
4 LMNB1 NM_005573.4(LMNB1):c.*189T>G SNV Uncertain significance 905852 5:126172145-126172145 5:126836453-126836453
5 LMNB1 NM_005573.4(LMNB1):c.*270T>C SNV Uncertain significance 905853 5:126172226-126172226 5:126836534-126836534
6 LMNB1 NM_005573.4(LMNB1):c.*284T>G SNV Uncertain significance 905854 5:126172240-126172240 5:126836548-126836548
7 LMNB1 NM_005573.4(LMNB1):c.-76G>T SNV Uncertain significance 906293 5:126113125-126113125 5:126777433-126777433
8 LMNB1 NM_005573.4(LMNB1):c.*301T>C SNV Uncertain significance 906362 5:126172257-126172257 5:126836565-126836565
9 LMNB1 NM_005573.4(LMNB1):c.*631G>A SNV Uncertain significance 906363 5:126172587-126172587 5:126836895-126836895
10 LMNB1 NM_005573.4(LMNB1):c.*634A>G SNV Uncertain significance 906364 5:126172590-126172590 5:126836898-126836898
11 LMNB1 NM_005573.4(LMNB1):c.*640G>A SNV Uncertain significance 906365 5:126172596-126172596 5:126836904-126836904
12 LMNB1 NM_005573.4(LMNB1):c.775C>T (p.Leu259=) SNV Uncertain significance 907307 5:126146004-126146004 5:126810312-126810312
13 LMNB1 NM_005573.4(LMNB1):c.853A>G (p.Thr285Ala) SNV Uncertain significance 907308 5:126147504-126147504 5:126811812-126811812
14 LMNB1 NM_005573.4(LMNB1):c.987T>C (p.Ala329=) SNV Uncertain significance 907309 5:126154661-126154661 5:126818969-126818969
15 LMNB1 NM_005573.4(LMNB1):c.1010G>A (p.Arg337His) SNV Uncertain significance 907310 5:126154684-126154684 5:126818992-126818992
16 LMNB1 NM_005573.4(LMNB1):c.1387-3T>C SNV Uncertain significance 350618 rs886059859 5:126158470-126158470 5:126822778-126822778
17 LMNB1 NM_005573.4(LMNB1):c.1161-6A>G SNV Uncertain significance 976611 5:126156596-126156596 5:126820904-126820904
18 LMNB1 NM_005573.4(LMNB1):c.-159C>G SNV Uncertain significance 350610 rs886059857 5:126113042-126113042 5:126777350-126777350
19 LMNB1 NM_005573.4(LMNB1):c.*629G>A SNV Uncertain significance 350626 rs761208282 5:126172585-126172585 5:126836893-126836893
20 LMNB1 NM_005573.4(LMNB1):c.*629G>C SNV Uncertain significance 350627 rs761208282 5:126172585-126172585 5:126836893-126836893
21 LMNB1 NM_005573.4(LMNB1):c.411A>T (p.Glu137Asp) SNV Uncertain significance 931753 5:126140519-126140519 5:126804827-126804827
22 LMNB1 NM_005573.4(LMNB1):c.1190G>A (p.Arg397His) SNV Likely benign 350617 rs746416284 5:126156631-126156631 5:126820939-126820939
23 LMNB1 NM_005573.4(LMNB1):c.672A>G (p.Glu224=) SNV Likely benign 350614 rs372510778 5:126145901-126145901 5:126810209-126810209
24 LMNB1 NM_005573.4(LMNB1):c.414T>C (p.Tyr138=) SNV Benign 66614 rs3749830 5:126140522-126140522 5:126804830-126804830
25 LMNB1 NM_005573.4(LMNB1):c.*518T>C SNV Benign 350625 rs185784874 5:126172474-126172474 5:126836782-126836782
26 LMNB1 NM_005573.4(LMNB1):c.1023C>T (p.Asp341=) SNV Benign 350616 rs886059858 5:126154697-126154697 5:126819005-126819005
27 LMNB1 NM_005573.4(LMNB1):c.*691A>G SNV Benign 350628 rs77429268 5:126172647-126172647 5:126836955-126836955
28 LMNB1 NM_005573.4(LMNB1):c.-314C>T SNV Benign 350608 rs561989552 5:126112887-126112887 5:126777195-126777195
29 LMNB1 NM_005573.4(LMNB1):c.*503A>T SNV Benign 350624 rs181936031 5:126172459-126172459 5:126836767-126836767
30 LMNB1 NM_005573.4(LMNB1):c.279C>T (p.Leu93=) SNV Benign 350612 rs74362780 5:126113479-126113479 5:126777787-126777787
31 LMNB1 NM_005573.4(LMNB1):c.852T>C (p.Ser284=) SNV Benign 66615 rs61726489 5:126147503-126147503 5:126811811-126811811
32 LMNB1 NM_005573.4(LMNB1):c.*43T>C SNV Benign 350622 rs1051643 5:126171999-126171999 5:126836307-126836307
33 LMNB1 NM_005573.4(LMNB1):c.*239C>T SNV Benign 350623 rs1051644 5:126172195-126172195 5:126836503-126836503
34 LMNB1 NM_005573.4(LMNB1):c.141C>T (p.Ile47=) SNV Benign 350611 rs755177047 5:126113341-126113341 5:126777649-126777649
35 LMNB1 NM_005573.4(LMNB1):c.*18C>T SNV Benign 66612 rs2230151 5:126171974-126171974 5:126836282-126836282
36 LMNB1 NM_005573.4(LMNB1):c.-298G>T SNV Benign 350609 rs111865788 5:126112903-126112903 5:126777211-126777211
37 LMNB1 NM_005573.4(LMNB1):c.1178G>A (p.Ser393Asn) SNV Benign 976612 5:126156619-126156619 5:126820927-126820927
38 LMNB1 NM_005573.4(LMNB1):c.432G>A (p.Ser144=) SNV Benign 129486 rs34224885 5:126140540-126140540 5:126804848-126804848
39 LMNB1 NM_005573.4(LMNB1):c.1560G>A (p.Ser520=) SNV Benign 350620 rs6875053 5:126161748-126161748 5:126826056-126826056
40 LMNB1 NM_005573.4(LMNB1):c.1492-11G>T SNV Benign 350619 rs201050320 5:126161669-126161669 5:126825977-126825977
41 LMNB1 NM_005573.4(LMNB1):c.642+10T>C SNV Benign 350613 rs200907573 5:126141398-126141398 5:126805706-126805706
42 LMNB1 NM_005573.4(LMNB1):c.*15T>C SNV Benign 350621 rs140296800 5:126171971-126171971 5:126836279-126836279
43 LMNB1 NM_005573.4(LMNB1):c.1502C>T (p.Ala501Val) SNV Benign 66613 rs36105360 5:126161690-126161690 5:126825998-126825998
44 LMNB1 NM_005573.4(LMNB1):c.700C>T (p.Arg234Cys) SNV Benign 907306 5:126145929-126145929 5:126810237-126810237
45 LMNB1 NM_005573.4(LMNB1):c.60G>A (p.Thr20=) SNV Benign 906294 5:126113260-126113260 5:126777568-126777568

Expression for Autosomal Dominant Leukodystrophy with Autonomic Disease

Search GEO for disease gene expression data for Autosomal Dominant Leukodystrophy with Autonomic Disease.

Pathways for Autosomal Dominant Leukodystrophy with Autonomic Disease

GO Terms for Autosomal Dominant Leukodystrophy with Autonomic Disease

Sources for Autosomal Dominant Leukodystrophy with Autonomic Disease

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
70 Tocris
72 UMLS via Orphanet
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