Klippel-trenaunay Syndrome malady

NIH Rare Diseases: Klippel Trenaunay syndrome is a condition that affects the development of blood vessels, soft tissues, and bones. This condition has three characteristic features: a red birthmark called a port-wine stain, abnormal overgrowth of soft tissues and bones, and vein malformations. A port-wine stain is a type of birthmark caused by swelling of the small blood vessels near the surface of the skin. The overgrowth of bones and soft tissues usually begins in infancy and is most often limited to one leg. However, overgrowth can also affect the arms or, rarely, the trunk. The abnormal growth can cause pain, a feeling of heaviness, and reduced movement in the affected area. The vein malformations include varicose veins and malformations of deep veins in the limbs. The cause of Klippel-Trenaunay syndrome is unknown. This condition is almost always sporadic, which means that it occurs in people with no history of the disorder in their family.³⁰

MalaCards: Klippel-trenaunay Syndrome, also known as klippel-trenaunay-weber syndrome, is related to weber syndrome and retinitis. An important gene associated with Klippel-trenaunay Syndrome is AGGF1 (angiogenic factor with G patch and FHA domains 1), and among its related pathways are Angiogenesis and Antioxidant Action of Vitamin-C. Affiliated tissues include skin, and related mouse phenotypes are pigmentation and vision/eye.

Genetics Home Reference: Klippel-Trenaunay syndrome is a condition that affects the development of blood vessels, soft tissues, and bones. The disorder has three characteristic features: a red birthmark called a port-wine stain, abnormal overgrowth of soft tissues and bones, and vein malformations.¹⁷

Aliases & Descriptions:

klippel-trenaunay syndrome 6 7 30 17 8 32 klippel-trenaunay-weber syndrome 6 30 33 ktw syndrome 30 16 17 kts 30 16 17 angio-osteohypertrophy syndrome 30 17 weber-klippel-trenaunay 30 16

congenital dysplastic angiopathy 17 angioosteohypertrophy syndrome 6 haemangiectatic hypertrophy 6 neonatal hemochromatosis 43 weber syndrome 43 angiectasis 43

Disease types for klippel-trenaunay syndrome family:

klippel-trenaunay syndrome (kts)

Diseases related to klippel-trenaunay syndrome by text searches and GeneDecks gene sharing:

(show top 50)    (show all 194)

id	Related Disease	Score	Top Affiliating Genes
1	weber syndrome	32.6	RASA1, ACVRL1, SERPINC1
2	retinitis	23.0	SERPINC1, PDCD10, ACVRL1, NDP, KRIT1, NOTCH4
3	yellow nail syndrome	13.3	FOXC2, SOX18
4	glomuvenous malformations	13.3	KRIT1, GLMN
5	cerebral angioma	13.3	KRIT1, CCM2
6	lymphedema, congenital	13.3	FLT4, FOXC2
7	hereditary lymphedema	13.2	FLT4, FOXC2
8	hypotrichosis	13.1	SOX18, FLT4, FOXC2
9	cerebral cavernous malformation, familial	13.1	PDCD10, KRIT1, CCM2
10	cavernous hemangioma of orbit	13.1	PDCD10, KRIT1, CCM2
11	telangiectasis	13.0	NDP, SOX18, ACVRL1
12	glomus tumor	13.0	GLMN, KRIT1
13	lymphedema	12.9	FOXC2, GLMN, SOX18, FLT4
14	cerebral cavernous malformations	12.9	CCM2, KRIT1, PDCD10
15	cavernous malformation	12.9	CCM2, KRIT1, PDCD10
16	capillary malformations	12.9	RASA1, KRIT1
17	proteus syndrome	12.8	SYNGAP1, AGGF1, GLMN, PDCD10
18	tufted angioma	12.7	FLT4, TEK
19	glomangioma	12.7	TEK, GLMN
20	arteriovenous malformation	12.6	ACVRL1, TEK
21	headache	12.6	CCM2, PDCD10, KRIT1
22	capillary hemangioma	12.5	FLT4, TEK
23	cerebrovascular accident	12.1	SERPINC1, CCM2, PDCD10, NOTCH4, KRIT1
24	cavernous hemangioma of face	12.1	TEK, KRIT1
25	venous malformations	12.1	PDCD10, KRIT1, TEK, GLMN, CCM2
26	hemangioma	12.0	TEK, NOTCH4, KRIT1, FLT4
27	vascular malformations	12.0	ACVRL1, KRIT1, GLMN, CCM2, TEK
28	vascular disease	11.4	TEK, AGGF1, SERPINC1, KRIT1, ACVRL1
29	atherosclerosis	11.1	KRIT1, ACVRL1, SOX18, TEK, FLT4, SERPINC1
30	ischemia	11.0	TEK, KRIT1, SERPINC1, TNFSF12, SYNGAP1, FLT4
31	pancreatic cancer	10.4	ACVRL1, FLT4, TEK, NOTCH4, SOX18, RASA1
32	cerebritis	10.0	KRIT1, NOTCH4, SYNGAP1, TEK, TNFSF12, SERPINC1
33	lung carcinoma	9.6	SERPINC1, SEMA4B, RASA1, SOX18, KRIT1, NOTCH4
34	sturge-weber syndrome	9.5
35	neonatal hemochromatosis	9.2
36	klippel-trenaunay syndrome (kts)	9.1
37	parkes weber syndrome	8.7
38	antithrombin iii deficiency	7.6
39	hemimegalencephaly	7.6
40	parkes weber syndrome, rasa1-related	7.3
41	hemochromatosis	7.3
42	neuronitis	7.1
43	wilms tumor	7.1
44	breast cancer	6.2
45	carcinoma	6.2
46	frasier syndrome	6.2
47	leukemia	6.2
48	acvrl1-related hereditary hemorrhagic telangiectasia	5.9
49	glaucoma	5.9
50	heterochromia iridis	5.9

Approved drugs:

Drug clinical trials:

Genetic tests related to klippel-trenaunay syndrome:

id	Genetic test	Affiliating Genes
1	Klippel-trenaunay Syndrome clinical/research

MalaCards organs/tissues related to klippel-trenaunay syndrome:

²²

MGI Mouse Phenotypes related to klippel-trenaunay syndrome:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	pigmentation phenotype	MP:0001186	9.2	SOX18, NDP, FOXC2, SERPINC1
2	vision/eye phenotype	MP:0005391	8.5	NDP, KRIT1, CCM2, FOXC2, SERPINC1, PDCD10
3	craniofacial phenotype	MP:0005382	8.3	ACVRL1, KRIT1, GLMN, CCM2, FOXC2, RASA1
4	muscle phenotype	MP:0005369	8.3	TEK, CCM2, FLT4, FOXC2, PDCD10, ACVRL1
5	homeostasis/metabolism phenotype	MP:0005376	6.8	SOX18, ACVRL1, NOTCH4, TEK, GLMN, CCM2
6	growth/size phenotype	MP:0005378	6.6	SOX18, SYNGAP1, ACVRL1, NOTCH4, TEK, GLMN
7	embryogenesis phenotype	MP:0005380	6.4	ACVRL1, KRIT1, NOTCH4, TEK, GLMN, CCM2
8	mortality/aging	MP:0010768	6.2	TEK, KRIT1, ACVRL1, SYNGAP1, SOX18, GLMN
9	cardiovascular system phenotype	MP:0005385	5.9	PDCD10, SOX18, ACVRL1, NDP, KRIT1, NOTCH4
10	nervous system phenotype	MP:0003631	5.5	NOTCH4, KRIT1, NDP, ACVRL1, SYNGAP1, TEK

Articles related to klippel-trenaunay syndrome:

id	Title	Authors	Year	Affiliating Genes
1	Klippel-Trenaunay syndrome associated with antithrombin III deficiency (18926244)	Grira M.... Benammou S.	2008	SERPINC1
2	Identification of association of common AGGF1 variants with susceptibility for Klippel-Trenaunay syndrome using the structure association program. (18564129)	Hu Y.... Wang Q.K.	2008	AGGF1
3	Klippel-Trenaunay syndrome: a multisystem disorder possibly resulting from a pathogenic gene for vascular and tissue overgrowth. (16911369)	Kihiczak G.G.... Janniger C.K.	2006	AGGF1
4	Biomedicine and diseases: the Klippel-Trenaunay syndrome, vascular anomalies and vascular morphogenesis. (15905966)	Timur A.A.... Wang Q.	2005	FLT4, TEK, ACVRL1
5	Identification of an angiogenic factor that when mutated causes susceptibility to Klippel-Trenaunay syndrome. (14961121)	Tian X.-L.... Wang Q.	2004	AGGF1, TNFSF12

Genes related to klippel-trenaunay syndrome according to GeneCards:

(show all 18)

id	Symbol	Description	Score	GeneCards Section Context
1	AGGF1	angiogenic factor with G patch and FHA domains 1	11.1	Summaries, Publications, Orthologs
2	SOX18	SRY (sex determining region Y)-box 18	11.1	Publications
3	GLMN	glomulin, FKBP associated protein	11.1	Publications
4	FOXC2	forkhead box C2 (MFH-1, mesenchyme forkhead 1)	11.1	Publications
5	PDCD10	programmed cell death 10	11.1	Publications
6	CCM2	cerebral cavernous malformation 2	11.1	Publications
7	FLT4	fms-related tyrosine kinase 4	11.1	Publications
8	KRIT1	KRIT1, ankyrin repeat containing	11.1	Publications
9	TNFSF12	tumor necrosis factor (ligand) superfamily, member 12	11.0	Publications
10	NDP	Norrie disease (pseudoglioma)	11.0	Publications
11	ACVRL1	activin A receptor type II-like 1	11.0	Publications
12	SYNGAP1	synaptic Ras GTPase activating protein 1	11.0
13	SEMA4B	sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4B	11.0
14	NOTCH4	notch 4	11.0	Publications
15	CMC1	COX assembly mitochondrial protein 1 homolog (S. cerevisiae)	11.0	Disorders
16	RASA1	RAS p21 protein activator (GTPase activating protein) 1	11.0
17	TEK	TEK tyrosine kinase, endothelial	11.0	Publications
18	SERPINC1	serpin peptidase inhibitor, clade C (antithrombin), member 1	11.0	Publications

Pathways related to klippel-trenaunay syndrome according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	Angiogenesis3	8.6	NOTCH4, TEK, FLT4
2	Antioxidant Action of Vitamin-C36	8.4	ACVRL1, TEK, TNFSF12, FLT4, SEMA4B
3	Ras Pathway36	8.4	SEMA4B, RASA1, FLT4, TEK
4	p38 Signaling36	8.3	ACVRL1, TEK, TNFSF12, FLT4, SEMA4B
5	Akt Signaling36	8.2	SEMA4B, FLT4, TNFSF12, TEK, ACVRL1
6	Molecular Mechanisms of Cancer36	6.8	SEMA4B, SOX18, SYNGAP1, ACVRL1, NOTCH4, TEK

Biological processes related to klippel-trenaunay syndrome according to GeneDecks:

(show all 15)

id	Name	GO ID	Score	Top Affiliating Genes
1	lymphatic endothelial cell differentiation	GO:060836	10.1	ACVRL1, SOX18
2	endothelial tube morphogenesis	GO:061154	10.1	CCM2, ACVRL1
3	vasculature development	GO:001944	10.0	FLT4, SOX18
4	negative regulation of endothelial cell differentiation	GO:045602	9.9	ACVRL1, NOTCH4
5	negative regulation of endothelial cell migration	GO:010596	9.7	KRIT1, ACVRL1
6	lymphangiogenesis	GO:001946	9.7	FOXC2, FLT4, ACVRL1, SOX18
7	negative regulation of endothelial cell apoptotic process	GO:2000352	9.5	TEK, KRIT1
8	positive regulation of endothelial cell migration	GO:010595	9.4	FOXC2, FLT4, TEK
9	sprouting angiogenesis	GO:002040	9.4	FLT4, TEK
10	vasculogenesis	GO:001570	9.2	SOX18, AGGF1, GLMN, CCM2, RASA1
11	positive regulation of angiogenesis	GO:045766	9.2	AGGF1, TEK, TNFSF12
12	positive regulation of transcription, DNA-dependent	GO:045893	9.1	SOX18, ACVRL1, NDP, NOTCH4, FOXC2
13	positive regulation of endothelial cell proliferation	GO:001938	8.8	AGGF1, ACVRL1, TEK, TNFSF12, FLT4
14	negative regulation of apoptotic process	GO:043066	8.5	SYNGAP1, TEK, FLT4, PDCD10
15	angiogenesis	GO:001525	8.4	PDCD10, SOX18, AGGF1, ACVRL1, KRIT1, TEK

Molecular functions related to klippel-trenaunay syndrome according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	protein binding	GO:005515	5.9	PDCD10, ACVRL1, KRIT1, NOTCH4, TEK, TNFSF12