MCID: LYS021
MIFTS: 38

Loeys-Dietz Syndrome 3

Categories: Genetic diseases, Rare diseases, Cardiovascular diseases, Bone diseases

Aliases & Classifications for Loeys-Dietz Syndrome 3

MalaCards integrated aliases for Loeys-Dietz Syndrome 3:

Name: Loeys-Dietz Syndrome 3 57 75 29 6 73
Loeys-Dietz Syndrome with Osteoarthritis 57 53 75
Aneurysms-Osteoarthritis Syndrome 57 53 75
Lds3 57 53 75
Aneurysm-Osteoarthritis Syndrome 53 59
Loeys-Dietz Syndrome, Type 3 53 13
Loeys-Dietz Syndrome, Type 1c, Formerly; Lds1c, Formerly 57
Loeys-Dietz Syndrome, Type 1c, Formerly 57
Aneurysm - Osteoarthritis Syndrome 53
Syndrome, Loeys-Dietz, Type 3 40
Loeys-Dietz Syndrome Type 3 53
Loeys-Dietz Syndrome 1c 75
Lds1c, Formerly 57
Lds1c 75
Aos 75

Characteristics:

Orphanet epidemiological data:

59
aneurysm-osteoarthritis syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
loeys-dietz syndrome 3:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Loeys-Dietz Syndrome 3

UniProtKB/Swiss-Prot : 75 Loeys-Dietz syndrome 3: An aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Patients with LDS3 also manifest early-onset osteoarthritis. They lack craniosynostosis and mental retardation.

MalaCards based summary : Loeys-Dietz Syndrome 3, also known as loeys-dietz syndrome with osteoarthritis, is related to adams-oliver syndrome and adams-oliver syndrome 1. An important gene associated with Loeys-Dietz Syndrome 3 is SMAD3 (SMAD Family Member 3), and among its related pathways/superpathways are Toll-like Receptor Signaling Pathway and Mesodermal Commitment Pathway. Affiliated tissues include bone and skin, and related phenotypes are hypertelorism and high palate

Description from OMIM: 613795

Related Diseases for Loeys-Dietz Syndrome 3

Graphical network of the top 20 diseases related to Loeys-Dietz Syndrome 3:



Diseases related to Loeys-Dietz Syndrome 3

Symptoms & Phenotypes for Loeys-Dietz Syndrome 3

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism

Abdomen External Features:
inguinal hernia
umbilical hernia

Skeletal Feet:
pes planus
foot osteoarthritis

Cardiovascular Heart:
left ventricular hypertrophy
mitral valve prolapse
atrial fibrillation
aortic insufficiency
mitral valve regurgitation
more
Skeletal Pelvis:
protrusio acetabuli
hip osteoarthritis

Genitourinary Internal Genitalia Female:
uterine prolapse

Skin Nails Hair Skin:
easy bruisability
atrophic scarring
striae
skin velvety

Chest Ribs Sternum Clavicles And Scapulae:
pectus deformity

Skeletal:
osteoporosis (rare)

Skeletal Spine:
scoliosis
dural ectasia
spondylolisthesis
intervertebral disc degeneration
facet joint osteoarthritis
more
Head And Neck Teeth:
dental malocclusion

Cardiovascular Vascular:
aortic dissection
aortic aneurysm
arterial tortuosity
arterial aneurysm
persistent ductus arteriosus (rare)
more
Skeletal Hands:
arachnodactyly
camptodactyly
hand osteoarthritis

Skeletal Limbs:
joint laxity
osteochondritis dissecans
long bone overgrowth (dolichostenomelia)
knee osteoarthritis
meniscal lesions
more
Head And Neck Mouth:
high-arched palate
cleft palate (rare)
abnormal uvula

Genitourinary Bladder:
bladder prolapse

Abdomen Gastrointestinal:
bowel prolapse


Clinical features from OMIM:

613795

Human phenotypes related to Loeys-Dietz Syndrome 3:

32 (show all 33)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 32 HP:0000316
2 high palate 32 HP:0000218
3 scoliosis 32 HP:0002650
4 inguinal hernia 32 HP:0000023
5 dental malocclusion 32 HP:0000689
6 umbilical hernia 32 HP:0001537
7 pes planus 32 HP:0001763
8 osteoporosis 32 occasional (7.5%) HP:0000939
9 cleft palate 32 occasional (7.5%) HP:0000175
10 patent ductus arteriosus 32 occasional (7.5%) HP:0001643
11 aortic dissection 32 HP:0002647
12 mitral regurgitation 32 HP:0001653
13 left ventricular hypertrophy 32 HP:0001712
14 striae distensae 32 HP:0001065
15 arachnodactyly 32 HP:0001166
16 mitral valve prolapse 32 HP:0001634
17 protrusio acetabuli 32 HP:0003179
18 dural ectasia 32 HP:0100775
19 spondylolisthesis 32 HP:0003302
20 joint laxity 32 HP:0001388
21 bruising susceptibility 32 HP:0000978
22 pulmonic stenosis 32 occasional (7.5%) HP:0001642
23 abnormality of the sternum 32 HP:0000766
24 atrial fibrillation 32 HP:0005110
25 aortic regurgitation 32 HP:0001659
26 camptodactyly 32 HP:0012385
27 aortic aneurysm 32 HP:0004942
28 intervertebral disc degeneration 32 HP:0008419
29 uterine prolapse 32 HP:0000139
30 arterial tortuosity 32 HP:0005116
31 hip osteoarthritis 32 HP:0008843
32 osteochondritis dissecans 32 HP:0010886
33 knee osteoarthritis 32 HP:0005086

Drugs & Therapeutics for Loeys-Dietz Syndrome 3

Search Clinical Trials , NIH Clinical Center for Loeys-Dietz Syndrome 3

Genetic Tests for Loeys-Dietz Syndrome 3

Genetic tests related to Loeys-Dietz Syndrome 3:

# Genetic test Affiliating Genes
1 Loeys-Dietz Syndrome 3 29 SMAD3

Anatomical Context for Loeys-Dietz Syndrome 3

MalaCards organs/tissues related to Loeys-Dietz Syndrome 3:

41
Bone, Skin

Publications for Loeys-Dietz Syndrome 3

Articles related to Loeys-Dietz Syndrome 3:

# Title Authors Year
1
[Loeys-Dietz Syndrome, 3 generations, 4 familial cases]. ( 28737872 )
2017

Variations for Loeys-Dietz Syndrome 3

UniProtKB/Swiss-Prot genetic disease variations for Loeys-Dietz Syndrome 3:

75
# Symbol AA change Variation ID SNP ID
1 SMAD3 p.Thr261Ile VAR_065578 rs387906851
2 SMAD3 p.Arg287Trp VAR_065579 rs387906850
3 SMAD3 p.Glu239Lys VAR_067047 rs387906853
4 SMAD3 p.Arg279Lys VAR_067048 rs387906852
5 SMAD3 p.Ala112Val VAR_067051 rs387906854

ClinVar genetic disease variations for Loeys-Dietz Syndrome 3:

6
(show top 50) (show all 116)
# Gene Variation Type Significance SNP ID Assembly Location
1 SMAD3 NM_005902.3(SMAD3): c.859C> T (p.Arg287Trp) single nucleotide variant Pathogenic/Likely pathogenic rs387906850 GRCh37 Chromosome 15, 67473779: 67473779
2 SMAD3 NM_005902.3(SMAD3): c.859C> T (p.Arg287Trp) single nucleotide variant Pathogenic/Likely pathogenic rs387906850 GRCh38 Chromosome 15, 67181441: 67181441
3 SMAD3 NM_005902.3(SMAD3): c.741_742delAT (p.Phe248Profs) deletion Pathogenic rs587776880 GRCh38 Chromosome 15, 67181323: 67181324
4 SMAD3 NM_005902.3(SMAD3): c.741_742delAT (p.Phe248Profs) deletion Pathogenic rs587776880 GRCh37 Chromosome 15, 67473661: 67473662
5 SMAD3 NM_005902.3(SMAD3): c.782C> T (p.Thr261Ile) single nucleotide variant Pathogenic rs387906851 GRCh37 Chromosome 15, 67473702: 67473702
6 SMAD3 NM_005902.3(SMAD3): c.782C> T (p.Thr261Ile) single nucleotide variant Pathogenic rs387906851 GRCh38 Chromosome 15, 67181364: 67181364
7 SMAD3 NM_005902.3(SMAD3): c.653delA (p.Asn218Thrfs) deletion Pathogenic rs587776881 GRCh38 Chromosome 15, 67170599: 67170599
8 SMAD3 NM_005902.3(SMAD3): c.653delA (p.Asn218Thrfs) deletion Pathogenic rs587776881 GRCh37 Chromosome 15, 67462937: 67462937
9 SMAD3 NM_005902.3(SMAD3): c.836G> A (p.Arg279Lys) single nucleotide variant Pathogenic rs387906852 GRCh37 Chromosome 15, 67473756: 67473756
10 SMAD3 NM_005902.3(SMAD3): c.836G> A (p.Arg279Lys) single nucleotide variant Pathogenic rs387906852 GRCh38 Chromosome 15, 67181418: 67181418
11 SMAD3 NM_005902.3(SMAD3): c.313delG (p.Ala105Profs) deletion Pathogenic rs587776882 GRCh38 Chromosome 15, 67165001: 67165001
12 SMAD3 NM_005902.3(SMAD3): c.313delG (p.Ala105Profs) deletion Pathogenic rs587776882 GRCh37 Chromosome 15, 67457339: 67457339
13 SMAD3 NM_005902.3(SMAD3): c.1081G> T (p.Glu361Ter) single nucleotide variant Pathogenic rs387906856 GRCh37 Chromosome 15, 67479774: 67479774
14 SMAD3 NM_005902.3(SMAD3): c.1081G> T (p.Glu361Ter) single nucleotide variant Pathogenic rs387906856 GRCh38 Chromosome 15, 67187436: 67187436
15 SMAD3 NM_005902.3(SMAD3): c.455C> A (p.Pro152Gln) single nucleotide variant Uncertain significance rs375574124 GRCh37 Chromosome 15, 67457645: 67457645
16 SMAD3 NM_005902.3(SMAD3): c.455C> A (p.Pro152Gln) single nucleotide variant Uncertain significance rs375574124 GRCh38 Chromosome 15, 67165307: 67165307
17 SMAD6 NM_005585.4(SMAD6): c.120C> A (p.Gly40=) single nucleotide variant Benign rs149612008 GRCh38 Chromosome 15, 66703378: 66703378
18 SMAD6 NM_005585.4(SMAD6): c.120C> A (p.Gly40=) single nucleotide variant Benign rs149612008 GRCh37 Chromosome 15, 66995716: 66995716
19 SMAD6 NM_005585.4(SMAD6): c.120C> T (p.Gly40=) single nucleotide variant Benign rs149612008 GRCh38 Chromosome 15, 66703378: 66703378
20 SMAD6 NM_005585.4(SMAD6): c.120C> T (p.Gly40=) single nucleotide variant Benign rs149612008 GRCh37 Chromosome 15, 66995716: 66995716
21 SMAD6 NM_005585.4(SMAD6): c.264C> G (p.Gly88=) single nucleotide variant Likely benign rs547033777 GRCh38 Chromosome 15, 66703522: 66703522
22 SMAD6 NM_005585.4(SMAD6): c.264C> G (p.Gly88=) single nucleotide variant Likely benign rs547033777 GRCh37 Chromosome 15, 66995860: 66995860
23 SMAD6 NM_005585.4(SMAD6): c.447C> T (p.Ala149=) single nucleotide variant Benign rs181184476 GRCh37 Chromosome 15, 66996043: 66996043
24 SMAD6 NM_005585.4(SMAD6): c.447C> T (p.Ala149=) single nucleotide variant Benign rs181184476 GRCh38 Chromosome 15, 66703705: 66703705
25 SMAD6 NM_005585.4(SMAD6): c.817+9G> C single nucleotide variant Benign rs200726236 GRCh38 Chromosome 15, 66704084: 66704084
26 SMAD6 NM_005585.4(SMAD6): c.817+9G> C single nucleotide variant Benign rs200726236 GRCh37 Chromosome 15, 66996422: 66996422
27 SMAD6 NM_005585.4(SMAD6): c.909G> A (p.Thr303=) single nucleotide variant Benign rs139719094 GRCh37 Chromosome 15, 67008793: 67008793
28 SMAD6 NM_005585.4(SMAD6): c.909G> A (p.Thr303=) single nucleotide variant Benign rs139719094 GRCh38 Chromosome 15, 66716455: 66716455
29 SMAD3 NM_005902.3(SMAD3): c.228G> T (p.Gln76His) single nucleotide variant Uncertain significance rs886041046 GRCh37 Chromosome 15, 67457254: 67457254
30 SMAD3 NM_005902.3(SMAD3): c.228G> T (p.Gln76His) single nucleotide variant Uncertain significance rs886041046 GRCh38 Chromosome 15, 67164916: 67164916
31 SMAD6 NM_005585.4(SMAD6): c.711C> T (p.His237=) single nucleotide variant Benign rs144415105 GRCh38 Chromosome 15, 66703969: 66703969
32 SMAD6 NM_005585.4(SMAD6): c.711C> T (p.His237=) single nucleotide variant Benign rs144415105 GRCh37 Chromosome 15, 66996307: 66996307
33 SMAD6 NM_005585.4(SMAD6): c.841C> G (p.Arg281Gly) single nucleotide variant Likely benign rs200004068 GRCh38 Chromosome 15, 66711691: 66711691
34 SMAD6 NM_005585.4(SMAD6): c.841C> G (p.Arg281Gly) single nucleotide variant Likely benign rs200004068 GRCh37 Chromosome 15, 67004029: 67004029
35 SMAD6 NM_005585.4(SMAD6): c.1167C> T (p.Phe389=) single nucleotide variant Benign rs12591946 GRCh38 Chromosome 15, 66781211: 66781211
36 SMAD6 NM_005585.4(SMAD6): c.1167C> T (p.Phe389=) single nucleotide variant Benign rs12591946 GRCh37 Chromosome 15, 67073549: 67073549
37 SMAD6 NM_005585.4(SMAD6): c.75C> T (p.Gly25=) single nucleotide variant Uncertain significance rs755856670 GRCh37 Chromosome 15, 66995671: 66995671
38 SMAD6 NM_005585.4(SMAD6): c.75C> T (p.Gly25=) single nucleotide variant Uncertain significance rs755856670 GRCh38 Chromosome 15, 66703333: 66703333
39 SMAD6 NM_005585.4(SMAD6): c.290G> A (p.Gly97Glu) single nucleotide variant Uncertain significance rs566777509 GRCh38 Chromosome 15, 66703548: 66703548
40 SMAD6 NM_005585.4(SMAD6): c.290G> A (p.Gly97Glu) single nucleotide variant Uncertain significance rs566777509 GRCh37 Chromosome 15, 66995886: 66995886
41 SMAD6 NM_005585.4(SMAD6): c.956C> T (p.Ala319Val) single nucleotide variant Likely benign rs148705603 GRCh38 Chromosome 15, 66781000: 66781000
42 SMAD6 NM_005585.4(SMAD6): c.956C> T (p.Ala319Val) single nucleotide variant Likely benign rs148705603 GRCh37 Chromosome 15, 67073338: 67073338
43 SMAD6 NM_005585.4(SMAD6): c.61G> A (p.Asp21Asn) single nucleotide variant Benign rs188799901 GRCh37 Chromosome 15, 66995657: 66995657
44 SMAD6 NM_005585.4(SMAD6): c.61G> A (p.Asp21Asn) single nucleotide variant Benign rs188799901 GRCh38 Chromosome 15, 66703319: 66703319
45 SMAD6 NM_005585.4(SMAD6): c.362G> A (p.Cys121Tyr) single nucleotide variant Conflicting interpretations of pathogenicity rs80232004 GRCh38 Chromosome 15, 66703620: 66703620
46 SMAD6 NM_005585.4(SMAD6): c.362G> A (p.Cys121Tyr) single nucleotide variant Conflicting interpretations of pathogenicity rs80232004 GRCh37 Chromosome 15, 66995958: 66995958
47 SMAD6 NM_005585.4(SMAD6): c.79_84delAGCGGC (p.Ser27_Gly28del) deletion Uncertain significance GRCh38 Chromosome 15, 66703337: 66703342
48 SMAD6 NM_005585.4(SMAD6): c.79_84delAGCGGC (p.Ser27_Gly28del) deletion Uncertain significance GRCh37 Chromosome 15, 66995675: 66995680
49 SMAD6 NM_005585.4(SMAD6): c.841C> T (p.Arg281Trp) single nucleotide variant Uncertain significance rs200004068 GRCh38 Chromosome 15, 66711691: 66711691
50 SMAD6 NM_005585.4(SMAD6): c.841C> T (p.Arg281Trp) single nucleotide variant Uncertain significance rs200004068 GRCh37 Chromosome 15, 67004029: 67004029

Expression for Loeys-Dietz Syndrome 3

Search GEO for disease gene expression data for Loeys-Dietz Syndrome 3.

Pathways for Loeys-Dietz Syndrome 3

GO Terms for Loeys-Dietz Syndrome 3

Cellular components related to Loeys-Dietz Syndrome 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcription factor complex GO:0005667 8.62 SMAD3 SMAD6

Biological processes related to Loeys-Dietz Syndrome 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of apoptotic process GO:0043066 9.4 SMAD3 SMAD6
2 immune response GO:0006955 9.37 SMAD3 SMAD6
3 negative regulation of cell proliferation GO:0008285 9.32 SMAD3 SMAD6
4 transforming growth factor beta receptor signaling pathway GO:0007179 9.26 SMAD3 SMAD6
5 negative regulation of transforming growth factor beta receptor signaling pathway GO:0030512 9.16 SMAD3 SMAD6
6 ureteric bud development GO:0001657 8.96 SMAD3 SMAD6
7 positive regulation of pri-miRNA transcription by RNA polymerase II GO:1902895 8.62 SMAD3 SMAD6

Molecular functions related to Loeys-Dietz Syndrome 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin binding GO:0003682 9.37 SMAD3 SMAD6
2 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.32 SMAD3 SMAD6
3 ubiquitin protein ligase binding GO:0031625 9.26 SMAD3 SMAD6
4 transcription regulatory region DNA binding GO:0044212 9.16 SMAD3 SMAD6
5 R-SMAD binding GO:0070412 8.96 SMAD3 SMAD6
6 co-SMAD binding GO:0070410 8.62 SMAD3 SMAD6

Sources for Loeys-Dietz Syndrome 3

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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