LDS2
MCID: LYS018
MIFTS: 43

Loeys-Dietz Syndrome 2 (LDS2)

Categories: Bone diseases, Cardiovascular diseases, Eye diseases, Fetal diseases, Genetic diseases, Immune diseases, Rare diseases

Aliases & Classifications for Loeys-Dietz Syndrome 2

MalaCards integrated aliases for Loeys-Dietz Syndrome 2:

Name: Loeys-Dietz Syndrome 2 57 12 53 75 29 6 15
Marfan Syndrome Type 2 59 75 29 73
Lds2 57 12 75
Aat3 57 12 75
Aortic Aneurysm, Familial Thoracic 3 57 73
Loeys-Dietz Syndrome Type 2 53 73
Marfan Syndrome Type Ii 12 76
Mfs2 59 75
Aortic Aneurysm, Familial Thoracic 3; Aat3 57
Thoracic Aortic Aneurysms and Dissection 2 75
Familial Aortic Aneurysm Thoracic Type 3 75
Familial Throacic Aortic Aneurysm 3 12
Marfan Syndrome, Type Ii, Formerly 57
Syndrome, Loeys-Dietz, Type 2 40
Taad2 75

Characteristics:

Orphanet epidemiological data:

59
marfan syndrome type 2
Inheritance: Autosomal dominant; Age of onset: All ages; Age of death: any age;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity (see )
uncommon and rare features seen in the most severely affected patients


HPO:

32
loeys-dietz syndrome 2:
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Loeys-Dietz Syndrome 2

UniProtKB/Swiss-Prot : 75 Loeys-Dietz syndrome 2: An aortic aneurysm syndrome with widespread systemic involvement, characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. Some patients have craniosynostosis, exotropy, micrognathia and retrognathia, structural brain abnormalities, and intellectual deficit.

MalaCards based summary : Loeys-Dietz Syndrome 2, also known as marfan syndrome type 2, is related to loeys-dietz syndrome and subclavian artery aneurysm. An important gene associated with Loeys-Dietz Syndrome 2 is TGFBR2 (Transforming Growth Factor Beta Receptor 2), and among its related pathways/superpathways are Amino Acid metabolism and Amino acid synthesis and interconversion (transamination). Affiliated tissues include skin, brain and spleen, and related phenotypes are malar flattening and hypertelorism

Disease Ontology : 12 A Loeys-Dietz syndrome that has material basis in heterozygous mutation in the TGFBR2 gene on chromosome 3p24.

Wikipedia : 76 Loeys´┐Ż??Dietz syndrome (LDS) is an autosomal dominant genetic connective tissue disorder. It has... more...

Description from OMIM: 610168

Related Diseases for Loeys-Dietz Syndrome 2

Diseases in the Loeys-Dietz Syndrome family:

Loeys-Dietz Syndrome 1 Loeys-Dietz Syndrome 2
Loeys-Dietz Syndrome 3 Loeys-Dietz Syndrome 4
Loeys-Dietz Syndrome 5

Diseases related to Loeys-Dietz Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 loeys-dietz syndrome 31.8 MYH11 TGFBR2 TMPO
2 subclavian artery aneurysm 9.9 MYH11 TGFBR2
3 marfan syndrome 9.9
4 loeys-dietz syndrome 3 9.9 MYH11 TGFBR2
5 aortic aneurysm, familial thoracic 1 9.8 MYH11 TGFBR2
6 aortic aneurysm 9.8 MYH11 TGFBR2
7 aortic disease 9.7 MYH11 TGFBR2
8 loeys-dietz syndrome 1 9.5 GOT1 GPT2 MYH11 TGFBR2

Graphical network of the top 20 diseases related to Loeys-Dietz Syndrome 2:



Diseases related to Loeys-Dietz Syndrome 2

Symptoms & Phenotypes for Loeys-Dietz Syndrome 2

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
proptosis
blue sclerae
exotropia

Head And Neck Face:
micrognathia
retrognathia

Skeletal:
joint laxity
osteoporosis (in some patients)
low-impact fractures (in some patients)

Skeletal Hands:
arachnodactyly
brachydactyly
camptodactyly
contractures
postaxial polydactyly (rare)
more
Neurologic Central Nervous System:
mental retardation (uncommon)
developmental delay (uncommon)
chiari malformation (uncommon)
hydrocephalus (uncommon)

Abdomen External Features:
umbilical hernia (rare)
inguinal hernia (rare)

Growth Other:
dolichostenomelia (uncommon)

Skin Nails Hair Skin:
velvety texture
translucent skin

Skeletal Spine:
scoliosis

Cardiovascular Vascular:
patent ductus arteriosus
ascending aortic dissection
pulmonary artery aneurysm
ascending aortic aneurysm
arterial tortuosity, generalized
more
Skeletal Feet:
talipes equinovarus

Head And Neck Mouth:
bifid uvula
cleft palate (uncommon)

Skeletal Skull:
malar hypoplasia
craniosynostosis (uncommon)

Cardiovascular Heart:
atrial septal defect (uncommon)
mitral valve prolapse (uncommon)
bicuspid aortic valve (uncommon)
bicuspid pulmonary valve (rare)
quadricuspid pulmonary valve (rare)

Chest Ribs Sternum Clavicles And Scapulae:
pectus deformity


Clinical features from OMIM:

610168

Human phenotypes related to Loeys-Dietz Syndrome 2:

32 (show all 48)
# Description HPO Frequency HPO Source Accession
1 malar flattening 32 HP:0000272
2 hypertelorism 32 HP:0000316
3 pectus excavatum 32 HP:0000767
4 hydrocephalus 32 occasional (7.5%) HP:0000238
5 intellectual disability 32 occasional (7.5%) HP:0001249
6 scoliosis 32 HP:0002650
7 inguinal hernia 32 occasional (7.5%) HP:0000023
8 global developmental delay 32 occasional (7.5%) HP:0001263
9 pectus carinatum 32 HP:0000768
10 umbilical hernia 32 occasional (7.5%) HP:0001537
11 pes planus 32 HP:0001763
12 osteoporosis 32 occasional (7.5%) HP:0000939
13 cleft palate 32 occasional (7.5%) HP:0000175
14 micrognathia 32 HP:0000347
15 retrognathia 32 HP:0000278
16 patent ductus arteriosus 32 HP:0001643
17 atrial septal defect 32 occasional (7.5%) HP:0001631
18 bicuspid aortic valve 32 occasional (7.5%) HP:0001647
19 joint laxity 32 HP:0001388
20 talipes equinovarus 32 HP:0001762
21 arnold-chiari malformation 32 occasional (7.5%) HP:0002308
22 striae distensae 32 HP:0001065
23 arachnodactyly 32 HP:0001166
24 disproportionate tall stature 32 occasional (7.5%) HP:0001519
25 spontaneous pneumothorax 32 HP:0002108
26 mitral valve prolapse 32 occasional (7.5%) HP:0001634
27 protrusio acetabuli 32 HP:0003179
28 spondylolisthesis 32 HP:0003302
29 ascending aortic dissection 32 HP:0004933
30 brachydactyly 32 HP:0001156
31 proptosis 32 HP:0000520
32 craniosynostosis 32 occasional (7.5%) HP:0001363
33 blue sclerae 32 HP:0000592
34 bifid uvula 32 HP:0000193
35 camptodactyly 32 HP:0012385
36 syndactyly 32 occasional (7.5%) HP:0001159
37 exotropia 32 HP:0000577
38 dermal translucency 32 HP:0010648
39 absent distal phalanges 32 occasional (7.5%) HP:0005807
40 joint contracture of the hand 32 HP:0009473
41 pulmonary artery aneurysm 32 HP:0004937
42 postaxial polydactyly 32 occasional (7.5%) HP:0100259
43 polydactyly 32 occasional (7.5%) HP:0010442
44 dilatation of the cerebral artery 32 occasional (7.5%) HP:0004944
45 ascending tubular aorta aneurysm 32 HP:0004970
46 generalized arterial tortuosity 32 HP:0004955
47 descending thoracic aorta aneurysm 32 occasional (7.5%) HP:0004959
48 bicuspid pulmonary valve 32 occasional (7.5%) HP:0005182

MGI Mouse Phenotypes related to Loeys-Dietz Syndrome 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.02 GPT2 MYH11 TGFBR2 TMPO TRIO

Drugs & Therapeutics for Loeys-Dietz Syndrome 2

Search Clinical Trials , NIH Clinical Center for Loeys-Dietz Syndrome 2

Genetic Tests for Loeys-Dietz Syndrome 2

Genetic tests related to Loeys-Dietz Syndrome 2:

# Genetic test Affiliating Genes
1 Loeys-Dietz Syndrome 2 29 TGFBR2
2 Marfan Syndrome Type 2 29

Anatomical Context for Loeys-Dietz Syndrome 2

MalaCards organs/tissues related to Loeys-Dietz Syndrome 2:

41
Skin, Brain, Spleen, Uterus, Bone, Eye

Publications for Loeys-Dietz Syndrome 2

Articles related to Loeys-Dietz Syndrome 2:

# Title Authors Year
1
Fibulin-2: genetic mapping and exclusion as a candidate gene in Marfan syndrome type 2. ( 8946175 )
1996

Variations for Loeys-Dietz Syndrome 2

UniProtKB/Swiss-Prot genetic disease variations for Loeys-Dietz Syndrome 2:

75 (show all 23)
# Symbol AA change Variation ID SNP ID
1 TGFBR2 p.Leu308Pro VAR_022351 rs28934568
2 TGFBR2 p.Tyr336Asn VAR_022352 rs104893812
3 TGFBR2 p.Ala355Pro VAR_022353 rs104893813
4 TGFBR2 p.Gly357Trp VAR_022354 rs104893814
5 TGFBR2 p.Ser449Phe VAR_022358 rs104893807
6 TGFBR2 p.Arg528Cys VAR_022360 rs104893810
7 TGFBR2 p.Arg528His VAR_022361 rs104893815
8 TGFBR2 p.Arg537Cys VAR_022362 rs104893809
9 TGFBR2 p.Arg460Cys VAR_029760 rs104893811
10 TGFBR2 p.Arg460His VAR_029761 rs104893816
11 TGFBR2 p.His377Arg VAR_066724
12 TGFBR2 p.Asp446Asn VAR_066725 rs886039551
13 TGFBR2 p.Met457Lys VAR_066726
14 TGFBR2 p.Gly509Val VAR_066727 rs863223853
15 TGFBR2 p.Ile510Phe VAR_066728
16 TGFBR2 p.Ile510Ser VAR_066729
17 TGFBR2 p.Cys514Arg VAR_066730 rs193922664
18 TGFBR2 p.Trp521Arg VAR_066731
19 TGFBR2 p.Arg190His VAR_076167 rs780542125
20 TGFBR2 p.Asp247Val VAR_076168 rs761231369
21 TGFBR2 p.Thr325Pro VAR_076169
22 TGFBR2 p.Gly357Arg VAR_076170
23 TGFBR2 p.Thr530Ile VAR_076171

ClinVar genetic disease variations for Loeys-Dietz Syndrome 2:

6 (show top 50) (show all 169)
# Gene Variation Type Significance SNP ID Assembly Location
1 TGFBR2 NM_001024847.2(TGFBR2): c.1599G> A (p.Gln533=) single nucleotide variant Pathogenic rs121918715 GRCh37 Chromosome 3, 30730003: 30730003
2 TGFBR2 NM_001024847.2(TGFBR2): c.1599G> A (p.Gln533=) single nucleotide variant Pathogenic rs121918715 GRCh38 Chromosome 3, 30688511: 30688511
3 TGFBR2 NM_003242.5(TGFBR2): c.923T> C (p.Leu308Pro) single nucleotide variant Pathogenic rs28934568 GRCh37 Chromosome 3, 30713598: 30713598
4 TGFBR2 NM_003242.5(TGFBR2): c.923T> C (p.Leu308Pro) single nucleotide variant Pathogenic rs28934568 GRCh38 Chromosome 3, 30672106: 30672106
5 TGFBR2 NM_003242.5(TGFBR2): c.1346C> T (p.Ser449Phe) single nucleotide variant Pathogenic rs104893807 GRCh37 Chromosome 3, 30715688: 30715688
6 TGFBR2 NM_003242.5(TGFBR2): c.1346C> T (p.Ser449Phe) single nucleotide variant Pathogenic rs104893807 GRCh38 Chromosome 3, 30674196: 30674196
7 TGFBR2 NM_003242.5(TGFBR2): c.1609C> T (p.Arg537Cys) single nucleotide variant Pathogenic rs104893809 GRCh37 Chromosome 3, 30732996: 30732996
8 TGFBR2 NM_003242.5(TGFBR2): c.1609C> T (p.Arg537Cys) single nucleotide variant Pathogenic rs104893809 GRCh38 Chromosome 3, 30691504: 30691504
9 TGFBR2 NM_003242.5(TGFBR2): c.1006T> A (p.Tyr336Asn) single nucleotide variant Pathogenic rs104893812 GRCh37 Chromosome 3, 30713681: 30713681
10 TGFBR2 NM_003242.5(TGFBR2): c.1006T> A (p.Tyr336Asn) single nucleotide variant Pathogenic rs104893812 GRCh38 Chromosome 3, 30672189: 30672189
11 TGFBR2 NM_003242.5(TGFBR2): c.1063G> C (p.Ala355Pro) single nucleotide variant Pathogenic rs104893813 GRCh37 Chromosome 3, 30713738: 30713738
12 TGFBR2 NM_003242.5(TGFBR2): c.1063G> C (p.Ala355Pro) single nucleotide variant Pathogenic rs104893813 GRCh38 Chromosome 3, 30672246: 30672246
13 TGFBR2 NM_003242.5(TGFBR2): c.1069G> T (p.Gly357Trp) single nucleotide variant Pathogenic rs104893814 GRCh37 Chromosome 3, 30713744: 30713744
14 TGFBR2 NM_003242.5(TGFBR2): c.1069G> T (p.Gly357Trp) single nucleotide variant Pathogenic rs104893814 GRCh38 Chromosome 3, 30672252: 30672252
15 TGFBR2 NM_003242.5(TGFBR2): c.1583G> A (p.Arg528His) single nucleotide variant Pathogenic rs104893815 GRCh37 Chromosome 3, 30732970: 30732970
16 TGFBR2 NM_003242.5(TGFBR2): c.1583G> A (p.Arg528His) single nucleotide variant Pathogenic rs104893815 GRCh38 Chromosome 3, 30691478: 30691478
17 TGFBR2 NM_003242.5(TGFBR2): c.1582C> T (p.Arg528Cys) single nucleotide variant Pathogenic rs104893810 GRCh37 Chromosome 3, 30732969: 30732969
18 TGFBR2 NM_003242.5(TGFBR2): c.1582C> T (p.Arg528Cys) single nucleotide variant Pathogenic rs104893810 GRCh38 Chromosome 3, 30691477: 30691477
19 TGFBR2 TGFBR2, IVS1, A-G, -2 single nucleotide variant Pathogenic
20 TGFBR2 NM_003242.5(TGFBR2): c.1378C> T (p.Arg460Cys) single nucleotide variant Pathogenic rs104893811 GRCh37 Chromosome 3, 30715720: 30715720
21 TGFBR2 NM_003242.5(TGFBR2): c.1378C> T (p.Arg460Cys) single nucleotide variant Pathogenic rs104893811 GRCh38 Chromosome 3, 30674228: 30674228
22 TGFBR2 NM_003242.5(TGFBR2): c.1379G> A (p.Arg460His) single nucleotide variant Pathogenic rs104893816 GRCh37 Chromosome 3, 30715721: 30715721
23 TGFBR2 NM_003242.5(TGFBR2): c.1379G> A (p.Arg460His) single nucleotide variant Pathogenic rs104893816 GRCh38 Chromosome 3, 30674229: 30674229
24 TGFBR2 NM_001024847.2(TGFBR2): c.1472-2A> G single nucleotide variant Pathogenic rs587776770 GRCh37 Chromosome 3, 30729874: 30729874
25 TGFBR2 NM_001024847.2(TGFBR2): c.1472-2A> G single nucleotide variant Pathogenic rs587776770 GRCh38 Chromosome 3, 30688382: 30688382
26 TGFBR2 NM_003242.5(TGFBR2): c.1273A> G (p.Met425Val) single nucleotide variant Pathogenic rs104893817 GRCh37 Chromosome 3, 30715615: 30715615
27 TGFBR2 NM_003242.5(TGFBR2): c.1273A> G (p.Met425Val) single nucleotide variant Pathogenic rs104893817 GRCh38 Chromosome 3, 30674123: 30674123
28 TGFBR2 NM_003242.5(TGFBR2): c.1280C> T (p.Pro427Leu) single nucleotide variant Pathogenic rs104893818 GRCh37 Chromosome 3, 30715622: 30715622
29 TGFBR2 NM_003242.5(TGFBR2): c.1280C> T (p.Pro427Leu) single nucleotide variant Pathogenic rs104893818 GRCh38 Chromosome 3, 30674130: 30674130
30 TGFBR2 NM_003242.5(TGFBR2): c.1483C> T (p.Arg495Ter) single nucleotide variant Pathogenic rs104893819 GRCh37 Chromosome 3, 30729962: 30729962
31 TGFBR2 NM_003242.5(TGFBR2): c.1483C> T (p.Arg495Ter) single nucleotide variant Pathogenic rs104893819 GRCh38 Chromosome 3, 30688470: 30688470
32 TMPO NM_003276.2(TMPO): c.2068C> T (p.Arg690Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs17028450 GRCh37 Chromosome 12, 98928103: 98928103
33 TMPO NM_003276.2(TMPO): c.2068C> T (p.Arg690Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs17028450 GRCh38 Chromosome 12, 98534325: 98534325
34 TMPO NM_003276.2(TMPO): c.1434G> C (p.Lys478Asn) single nucleotide variant Benign/Likely benign rs35761089 GRCh37 Chromosome 12, 98927469: 98927469
35 TMPO NM_003276.2(TMPO): c.1434G> C (p.Lys478Asn) single nucleotide variant Benign/Likely benign rs35761089 GRCh38 Chromosome 12, 98533691: 98533691
36 TMPO NM_003276.2(TMPO): c.713T> G (p.Leu238Arg) single nucleotide variant Benign/Likely benign rs35998138 GRCh37 Chromosome 12, 98926748: 98926748
37 TMPO NM_003276.2(TMPO): c.713T> G (p.Leu238Arg) single nucleotide variant Benign/Likely benign rs35998138 GRCh38 Chromosome 12, 98532970: 98532970
38 TMPO NM_003276.2(TMPO): c.877T> G (p.Ser293Ala) single nucleotide variant Benign/Likely benign rs35645287 GRCh37 Chromosome 12, 98926912: 98926912
39 TMPO NM_003276.2(TMPO): c.877T> G (p.Ser293Ala) single nucleotide variant Benign/Likely benign rs35645287 GRCh38 Chromosome 12, 98533134: 98533134
40 TMPO NM_003276.2(TMPO): c.950C> G (p.Thr317Ser) single nucleotide variant Benign/Likely benign rs35969221 GRCh37 Chromosome 12, 98926985: 98926985
41 TMPO NM_003276.2(TMPO): c.950C> G (p.Thr317Ser) single nucleotide variant Benign/Likely benign rs35969221 GRCh38 Chromosome 12, 98533207: 98533207
42 TMPO NM_003276.2(TMPO): c.1246A> G (p.Lys416Glu) single nucleotide variant Benign/Likely benign rs11838270 GRCh37 Chromosome 12, 98927281: 98927281
43 TMPO NM_003276.2(TMPO): c.1246A> G (p.Lys416Glu) single nucleotide variant Benign/Likely benign rs11838270 GRCh38 Chromosome 12, 98533503: 98533503
44 TMPO NM_003276.2(TMPO): c.1471T> G (p.Ser491Ala) single nucleotide variant Benign/Likely benign rs80325832 GRCh37 Chromosome 12, 98927506: 98927506
45 TMPO NM_003276.2(TMPO): c.1471T> G (p.Ser491Ala) single nucleotide variant Benign/Likely benign rs80325832 GRCh38 Chromosome 12, 98533728: 98533728
46 TMPO NM_003276.2(TMPO): c.1632T> A (p.Ile544=) single nucleotide variant Benign/Likely benign rs12316677 GRCh37 Chromosome 12, 98927667: 98927667
47 TMPO NM_003276.2(TMPO): c.1632T> A (p.Ile544=) single nucleotide variant Benign/Likely benign rs12316677 GRCh38 Chromosome 12, 98533889: 98533889
48 TMPO NM_003276.2(TMPO): c.1957C> T (p.Leu653Phe) single nucleotide variant Conflicting interpretations of pathogenicity rs202035749 GRCh37 Chromosome 12, 98927992: 98927992
49 TMPO NM_003276.2(TMPO): c.1957C> T (p.Leu653Phe) single nucleotide variant Conflicting interpretations of pathogenicity rs202035749 GRCh38 Chromosome 12, 98534214: 98534214
50 TMPO NM_003276.2(TMPO): c.396T> A (p.Gly132=) single nucleotide variant Conflicting interpretations of pathogenicity rs397516844 GRCh37 Chromosome 12, 98921780: 98921780

Expression for Loeys-Dietz Syndrome 2

Search GEO for disease gene expression data for Loeys-Dietz Syndrome 2.

Pathways for Loeys-Dietz Syndrome 2

Pathways related to Loeys-Dietz Syndrome 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.22 GOT1 GPT2
2
Show member pathways
10.77 GOT1 GPT2
3 10.5 GOT1 GPT2
4
Show member pathways
10.04 GOT1 GPT2

GO Terms for Loeys-Dietz Syndrome 2

Biological processes related to Loeys-Dietz Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Notch signaling pathway GO:0007219 9.26 GOT1 TGFBR2
2 cellular amino acid biosynthetic process GO:0008652 9.16 GOT1 GPT2
3 biosynthetic process GO:0009058 8.96 GOT1 GPT2
4 2-oxoglutarate metabolic process GO:0006103 8.62 GOT1 GPT2

Molecular functions related to Loeys-Dietz Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 9.46 GOT1 GPT2 TGFBR2 TRIO
2 pyridoxal phosphate binding GO:0030170 8.96 GOT1 GPT2
3 transaminase activity GO:0008483 8.62 GOT1 GPT2

Sources for Loeys-Dietz Syndrome 2

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69 SNOMED-CT via HPO
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74 UMLS via Orphanet
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