MCID: HNN001
MIFTS: 51

Hennekam Syndrome

Categories: Blood diseases, Cardiovascular diseases, Fetal diseases, Immune diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Hennekam Syndrome

MalaCards integrated aliases for Hennekam Syndrome:

Name: Hennekam Syndrome 12 76 53 25 59 15
Hennekam Lymphangiectasia Lymphedema Syndrome 53 44 73
Lymphedema-Lymphangiectasia-Intellectual Disability Syndrome 25 59
Hennekam Lymphangiectasia-Lymphedema Syndrome 12 25
Intestinal Lymphagiectasia Lymphedema Intellectual Deficit Syndrome 53
Intestinal Lymphagiectasia-Lymphedema-Mental Retardation Syndrome 25
Lymphedem-Lymphangiectasia-Intellectual Disability Syndrome 12
Lymphangiectasies and Lymphedema Hennekam Type 53
Generalized Lymphatic Dysplasia 25

Characteristics:

Orphanet epidemiological data:

59
hennekam syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

Classifications:



Summaries for Hennekam Syndrome

NIH Rare Diseases : 53 Hennekam syndrome is a rare condition that affects the lymphatic system. Signs and symptoms of the condition are generally noticeable at birth and vary significantly from person to person, even within the same family. Affected people generally experience lymphangiectasia (lymphatic vessels that are abnormally expanded), lymphedema, and distinctive facial features (i.e. a flattened appearance to the middle of the face, puffy eyelids, widely spaced eyes, small ears, and a small mouth). Other common features include intellectual disability, growth delay, respiratory problems, camptodactyly (permanently bent fingers and toes) and cutaneous syndactyly (fusion of the skin between the fingers and toes). Hennekam syndrome is caused by changes (mutations) in the CCBE1 or FAT4 genes and is inherited in an autosomal recessive manner. Treatment is based on the signs and symptoms present in each person.

MalaCards based summary : Hennekam Syndrome, also known as hennekam lymphangiectasia lymphedema syndrome, is related to van maldergem syndrome 1 and lymphedema. An important gene associated with Hennekam Syndrome is CCBE1 (Collagen And Calcium Binding EGF Domains 1), and among its related pathways/superpathways are Nanog in Mammalian ESC Pluripotency and Pathways in cancer. Affiliated tissues include skin, eye and kidney, and related phenotypes are hypertelorism and low-set ears

Disease Ontology : 12 A lymphatic system disease characterized by he presence of intestinal lymphangiectasia, mental retardation, and characteristic facial anomalies. It is inherited in an autosomal recessive pattern. Most individuals with Hennekam syndrome have characteristic facial abnormalities, such as a flat face with accompanying puffy eyelids and hypertelorism; the nasal bridge is typically flat and the ears are typically small. Congenital extremity and genital lymphedema is present in most patients.

Genetics Home Reference : 25 Hennekam syndrome is an inherited disorder resulting from malformation of the lymphatic system, which is part of both the circulatory system and immune system. The lymphatic system consists of a network of vessels that transport lymph fluid and immune cells throughout the body.

Wikipedia : 76 Hennekam syndrome also known as intestinal lymphagiectasia�??lymphedema�??mental retardation syndrome,... more...

Related Diseases for Hennekam Syndrome

Diseases related to Hennekam Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 43)
# Related Disease Score Top Affiliating Genes
1 van maldergem syndrome 1 30.5 DCHS1 FAT4
2 lymphedema 30.5 CCBE1 FLT4 VEGFC
3 chylothorax, congenital 30.0 ALB FLT4
4 protein-losing enteropathy 29.7 ALB SERPINA1
5 van maldergem syndrome 29.4 ADAMTS2 ADAMTS3 CCBE1 CDH17 DCHS1 EGF
6 hennekam lymphangiectasia-lymphedema syndrome 2 12.9
7 hennekam lymphangiectasia-lymphedema syndrome 3 12.9
8 ausems wittebol-post hennekam syndrome 12.1
9 lymphedema, hereditary, iii 11.9
10 cleft lip-retinopathy syndrome 11.2
11 hennekam lymphangiectasia-lymphedema syndrome 1 11.0
12 cholestasis-lymphedema syndrome 10.2 ALB CCBE1
13 gorham's disease 10.1 FLT4 VEGFC
14 congenital lymphedema 10.1 FLT4 VEGFC
15 lymphatic malformations 10.1 FLT4 PROX1
16 lymphangiectasis 10.1
17 kaposiform hemangioendothelioma 10.1 FLT4 PROX1
18 interstitial emphysema 10.1 FLT4 PROX1
19 alveoli adenoma 10.1 FLT4 PROX1
20 hereditary lymphedema 10.1 FLT4 VEGFC
21 lymphatic system disease 10.1 CCBE1 FLT4 VEGFC
22 renal hypoplasia 10.0 DCHS1 FAT4
23 lymphangioma 10.0 FLT4 PROX1 VEGFC
24 chronic ulcer of skin 10.0 ALB EGF
25 hydrops fetalis, nonimmune 10.0
26 immune hydrops fetalis 10.0
27 lymphangiectasia, pulmonary, congenital 10.0
28 hydrops fetalis, nonimmune, and/or atrial septal defect 10.0
29 craniosynostosis 10.0
30 fetal edema 10.0
31 hydrops fetalis 10.0
32 cystic kidney disease 9.9 ALB EGF FAT4
33 gastritis, familial giant hypertrophic 9.9 ALB SERPINA1
34 constrictive pericarditis 9.9 ALB SERPINA1
35 hepatic tuberculosis 9.9 ALB SERPINA1
36 polyposis, skin pigmentation, alopecia, and fingernail changes 9.9 ALB SERPINA1
37 endodermal sinus tumor 9.9 ALB SERPINA1
38 cutaneous solitary mastocytoma 9.8 KITLG SERPINA1
39 ascites, chylous 9.8
40 blind loop syndrome 9.8 ALB SERPINA1
41 lymphangiosarcoma 9.8 FLT4 KITLG PROX1 VEGFC
42 large intestine cancer 9.7 ALB CDH17 EGF VEGFC
43 transient arthritis 9.7 ALB SERPINA1

Graphical network of the top 20 diseases related to Hennekam Syndrome:



Diseases related to Hennekam Syndrome

Symptoms & Phenotypes for Hennekam Syndrome

Human phenotypes related to Hennekam Syndrome:

59 32 (show top 50) (show all 51)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000316
2 low-set ears 59 32 hallmark (90%) Very frequent (99-80%) HP:0000369
3 finger syndactyly 59 32 occasional (7.5%) Occasional (29-5%) HP:0006101
4 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
5 seizures 59 32 frequent (33%) Frequent (79-30%) HP:0001250
6 respiratory insufficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0002093
7 gingival overgrowth 59 32 frequent (33%) Frequent (79-30%) HP:0000212
8 splenomegaly 59 32 frequent (33%) Frequent (79-30%) HP:0001744
9 recurrent respiratory infections 59 32 frequent (33%) Frequent (79-30%) HP:0002205
10 depressed nasal bridge 59 32 hallmark (90%) Very frequent (99-80%) HP:0005280
11 wide nasal bridge 59 32 hallmark (90%) Very frequent (99-80%) HP:0000431
12 malabsorption 59 32 hallmark (90%) Very frequent (99-80%) HP:0002024
13 ascites 59 32 frequent (33%) Frequent (79-30%) HP:0001541
14 ectopic kidney 59 32 occasional (7.5%) Occasional (29-5%) HP:0000086
15 retrognathia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000278
16 delayed eruption of teeth 59 32 hallmark (90%) Very frequent (99-80%) HP:0000684
17 narrow chest 59 32 frequent (33%) Frequent (79-30%) HP:0000774
18 epicanthus 59 32 frequent (33%) Frequent (79-30%) HP:0000286
19 lymphedema 59 32 hallmark (90%) Very frequent (99-80%) HP:0001004
20 hydrops fetalis 59 32 occasional (7.5%) Occasional (29-5%) HP:0001789
21 flat face 59 32 hallmark (90%) Very frequent (99-80%) HP:0012368
22 arteriovenous malformation 59 32 occasional (7.5%) Occasional (29-5%) HP:0100026
23 horseshoe kidney 59 32 occasional (7.5%) Occasional (29-5%) HP:0000085
24 external ear malformation 59 32 hallmark (90%) Very frequent (99-80%) HP:0008572
25 abnormality of the foot 59 32 occasional (7.5%) Occasional (29-5%) HP:0001760
26 decreased antibody level in blood 59 32 hallmark (90%) Very frequent (99-80%) HP:0004313
27 broad forehead 59 32 frequent (33%) Frequent (79-30%) HP:0000337
28 short philtrum 59 32 occasional (7.5%) Occasional (29-5%) HP:0000322
29 glaucoma 59 32 frequent (33%) Frequent (79-30%) HP:0000501
30 lymphopenia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001888
31 increased number of teeth 59 32 hallmark (90%) Very frequent (99-80%) HP:0011069
32 narrow mouth 59 32 occasional (7.5%) Occasional (29-5%) HP:0000160
33 conductive hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000405
34 hypocalcemia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002901
35 reduced number of teeth 59 32 hallmark (90%) Very frequent (99-80%) HP:0009804
36 benign neoplasm of the central nervous system 59 32 occasional (7.5%) Occasional (29-5%) HP:0100835
37 abnormality of dental morphology 59 32 hallmark (90%) Very frequent (99-80%) HP:0006482
38 pyloric stenosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002021
39 craniosynostosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0001363
40 camptodactyly of finger 59 32 occasional (7.5%) Occasional (29-5%) HP:0100490
41 pachygyria 59 32 occasional (7.5%) Occasional (29-5%) HP:0001302
42 lymphadenopathy 59 32 frequent (33%) Frequent (79-30%) HP:0002716
43 lymphangioma 59 32 hallmark (90%) Very frequent (99-80%) HP:0100764
44 chylothorax 59 32 occasional (7.5%) Occasional (29-5%) HP:0010310
45 erysipelas 59 32 frequent (33%) Frequent (79-30%) HP:0001055
46 sparse axillary hair 59 32 occasional (7.5%) Occasional (29-5%) HP:0002215
47 mild postnatal growth retardation 59 32 hallmark (90%) Very frequent (99-80%) HP:0001530
48 pericardial effusion 59 32 occasional (7.5%) Occasional (29-5%) HP:0001698
49 pulmonary lymphangiectasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0006521
50 abnormal facial shape 59 Very frequent (99-80%)

MGI Mouse Phenotypes related to Hennekam Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.92 ADAMTS3 ALB DCHS1 EGF FAT4 FLT4
2 cardiovascular system MP:0005385 9.91 ADAMTS3 DCHS1 FAT4 FLT4 KITLG PROX1
3 immune system MP:0005387 9.86 ADAMTS3 CCBE1 CDH17 EGF FLT4 KITLG
4 integument MP:0010771 9.63 ADAMTS2 ADAMTS3 CCBE1 EGF FLT4 KITLG
5 liver/biliary system MP:0005370 9.43 ADAMTS3 ALB CCBE1 FLT4 KITLG PROX1
6 mortality/aging MP:0010768 9.28 ADAMTS3 ALB CCBE1 DCHS1 FAT4 FLT4

Drugs & Therapeutics for Hennekam Syndrome

Search Clinical Trials , NIH Clinical Center for Hennekam Syndrome

Cochrane evidence based reviews: hennekam lymphangiectasia lymphedema syndrome

Genetic Tests for Hennekam Syndrome

Anatomical Context for Hennekam Syndrome

MalaCards organs/tissues related to Hennekam Syndrome:

41
Skin, Eye, Kidney

Publications for Hennekam Syndrome

Articles related to Hennekam Syndrome:

(show all 26)
# Title Authors Year
1
Van Maldergem syndrome and Hennekam syndrome: Further delineation of allelic phenotypes. ( 29681106 )
2018
2
Protein Losing Enteropathy in Hennekam Syndrome. ( 29327272 )
2018
3
Hennekam Syndrome: A Case Report. ( 29560340 )
2018
4
An additional case of Hennekam lymphangiectasia-lymphedema syndrome caused by loss-of-function mutation in ADAMTS3. ( 30450763 )
2018
5
A Multiplex Kindred with Hennekam Syndrome due to Homozygosity for a CCBE1 Mutation that does not Prevent Protein Expression. ( 26686525 )
2016
6
Expanding the genotypic spectrum of CCBE1 mutations in Hennekam syndrome. ( 27345729 )
2016
7
Intestinal Lymphangiestasia with Hennekam Syndrome. ( 26863383 )
2016
8
[A complicated case study: Hennekam syndrome]. ( 25616299 )
2015
9
A Rare Cause of Chylothorax: Hennekam Syndrome. ( 29404075 )
2015
10
A novel CCBE1 mutation leading to a mild form of hennekam syndrome: case report and review of the literature. ( 25925991 )
2015
11
Hennekam syndrome: a rare cause of primary lymphedema. ( 25148287 )
2014
12
Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome. ( 24913602 )
2014
13
Hennekam syndrome: a rare and often ignored cause of intestinal lymphangiectasia. ( 24870712 )
2014
14
Octreotide in Hennekam syndrome-associated intestinal lymphangiectasia. ( 23180957 )
2012
15
Cutaneous manifestations and massive genital involvement in Hennekam syndrome. ( 16780470 )
2006
16
Further delineation of Hennekam syndrome. ( 14564208 )
2003
17
Hennekam syndrome presenting as nonimmune hydrops fetalis, congenital chylothorax, and congenital pulmonary lymphangiectasia. ( 12794699 )
2003
18
Severe lymphedema, intestinal lymphangiectasia, seizures and mild mental retardation: further case of Hennekam syndrome with a severe phenotype. ( 12124738 )
2002
19
Lymphedema-lymphangiectasia-mental retardation (Hennekam) syndrome: a review. ( 12376947 )
2002
20
Early death in two sisters with Hennekam syndrome. ( 10925377 )
2000
21
Two brothers with Hennekam syndrome and cerebral abnormalities. ( 10649792 )
2000
22
Lymphoscintigraphic manifestations of Hennekam syndrome--a case report. ( 10609768 )
1999
23
Expansion of the phenotype in Hennekam syndrome: a case with new manifestations. ( 9217224 )
1997
24
Craniosynostosis and kidney malformation in a case of Hennekam syndrome. ( 7645602 )
1995
25
Protein-losing gastroenteropathy with facial anomaly and growth retardation: a mild case of Hennekam syndrome. ( 8465855 )
1993
26
Intestinal lymphangiectasia, lymphedema, mental retardation, and typical face: confirmation of the Hennekam syndrome. ( 1897580 )
1991

Variations for Hennekam Syndrome

Expression for Hennekam Syndrome

Search GEO for disease gene expression data for Hennekam Syndrome.

Pathways for Hennekam Syndrome

Pathways related to Hennekam Syndrome according to GeneCards Suite gene sharing:

(show all 17)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.78 CDH17 DCHS1 EGF FLT4 KITLG VEGFC
2 12.59 EGF FLT4 KITLG VEGFC
3 12.49 EGF FLT4 KITLG VEGFC
4
Show member pathways
12.4 EGF FLT4 KITLG VEGFC
5
Show member pathways
12.35 EGF FLT4 KITLG VEGFC
6
Show member pathways
12.13 EGF FLT4 KITLG VEGFC
7
Show member pathways
11.69 CDH17 DCHS1 EGF
8
Show member pathways
11.68 EGF FLT4 KITLG VEGFC
9 11.64 CDH17 DCHS1 EGF
10 11.45 FLT4 PROX1 VEGFC
11 11.43 EGF FLT4 KITLG VEGFC
12 11.15 ALB EGF KITLG PROX1 SERPINA1
13 11.01 DCHS1 FAT4
14 10.87 FLT4 VEGFC
15 10.82 EGF FLT4 VEGFC
16
Show member pathways
10.61 FLT4 VEGFC
17 10.46 CDH17 EGF FLT4 KITLG VEGFC

GO Terms for Hennekam Syndrome

Cellular components related to Hennekam Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 9.7 ADAMTS3 ALB CCBE1 EGF KITLG SERPINA1
2 extracellular region GO:0005576 9.61 ADAMTS2 ADAMTS3 ALB CCBE1 EGF FLT4
3 platelet alpha granule lumen GO:0031093 8.92 ALB EGF SERPINA1 VEGFC

Biological processes related to Hennekam Syndrome according to GeneCards Suite gene sharing:

(show all 23)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of cell proliferation GO:0008284 9.85 EGF FLT4 KITLG PROX1 VEGFC
2 homophilic cell adhesion via plasma membrane adhesion molecules GO:0007156 9.75 CDH17 DCHS1 FAT4
3 kidney development GO:0001822 9.73 DCHS1 FAT4 PROX1
4 lung development GO:0030324 9.71 ADAMTS2 CCBE1 PROX1
5 positive regulation of endothelial cell proliferation GO:0001938 9.69 FLT4 PROX1 VEGFC
6 collagen catabolic process GO:0030574 9.61 ADAMTS2 ADAMTS3
7 respiratory gaseous exchange GO:0007585 9.61 CCBE1 FLT4
8 digestive tract development GO:0048565 9.6 DCHS1 FAT4
9 hippo signaling GO:0035329 9.59 DCHS1 FAT4
10 positive regulation of vascular endothelial growth factor production GO:0010575 9.58 CCBE1 FLT4
11 positive regulation of endothelial cell migration GO:0010595 9.58 CCBE1 FLT4 PROX1
12 vascular endothelial growth factor signaling pathway GO:0038084 9.57 FLT4 VEGFC
13 respiratory system process GO:0003016 9.55 CCBE1 FLT4
14 ossification involved in bone maturation GO:0043931 9.52 DCHS1 FAT4
15 sprouting angiogenesis GO:0002040 9.5 CCBE1 FLT4 VEGFC
16 nephron development GO:0072006 9.49 DCHS1 FAT4
17 venous blood vessel morphogenesis GO:0048845 9.48 CCBE1 PROX1
18 platelet degranulation GO:0002576 9.46 ALB EGF SERPINA1 VEGFC
19 positive regulation of vascular endothelial growth factor signaling pathway GO:1900748 9.43 ADAMTS3 CCBE1
20 condensed mesenchymal cell proliferation GO:0072137 9.37 DCHS1 FAT4
21 positive regulation of lymphangiogenesis GO:1901492 9.26 CCBE1 VEGFC
22 lymph vessel development GO:0001945 9.13 CCBE1 FLT4 PROX1
23 lymphangiogenesis GO:0001946 8.8 CCBE1 FLT4 PROX1

Molecular functions related to Hennekam Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 growth factor activity GO:0008083 9.13 EGF KITLG VEGFC
2 calcium ion binding GO:0005509 9.02 CCBE1 CDH17 DCHS1 EGF FAT4

Sources for Hennekam Syndrome

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
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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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