MCID: HNN001
MIFTS: 50

Hennekam Syndrome

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

Aliases & Classifications for Hennekam Syndrome

MalaCards integrated aliases for Hennekam Syndrome:

Name: Hennekam Syndrome 12 72 49 24 55 14
Hennekam Lymphangiectasia Lymphedema Syndrome 49 41 69
Lymphedema-Lymphangiectasia-Intellectual Disability Syndrome 24 55
Hennekam Lymphangiectasia-Lymphedema Syndrome 12 24
Intestinal Lymphagiectasia Lymphedema Intellectual Deficit Syndrome 49
Intestinal Lymphagiectasia-Lymphedema-Mental Retardation Syndrome 24
Lymphedem-Lymphangiectasia-Intellectual Disability Syndrome 12
Lymphangiectasies and Lymphedema Hennekam Type 49
Generalized Lymphatic Dysplasia 24

Characteristics:

Orphanet epidemiological data:

55
hennekam syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

Classifications:



Summaries for Hennekam Syndrome

NIH Rare Diseases : 49 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. Last updated: 2/17/2016

MalaCards based summary : Hennekam Syndrome, also known as hennekam lymphangiectasia lymphedema syndrome, is related to van maldergem syndrome 1 and chylothorax, congenital, and has symptoms including hypertelorism, low-set ears and wide nasal bridge. 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 cardiovascular system and digestive/alimentary

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 : 24 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 : 72 Hennekam syndrome also known as intestinal lymphagiectasia–lymphedema–mental retardation syndrome, is an... more...

Related Diseases for Hennekam Syndrome

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:

55 31 (show top 50) (show all 51)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 55 31 hallmark (90%) Very frequent (99-80%) HP:0000316
2 low-set ears 55 31 hallmark (90%) Very frequent (99-80%) HP:0000369
3 wide nasal bridge 55 31 hallmark (90%) Very frequent (99-80%) HP:0000431
4 delayed eruption of teeth 55 31 hallmark (90%) Very frequent (99-80%) HP:0000684
5 lymphedema 55 31 hallmark (90%) Very frequent (99-80%) HP:0001004
6 intellectual disability 55 31 hallmark (90%) Very frequent (99-80%) HP:0001249
7 mild postnatal growth retardation 55 31 hallmark (90%) Very frequent (99-80%) HP:0001530
8 lymphopenia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001888
9 malabsorption 55 31 hallmark (90%) Very frequent (99-80%) HP:0002024
10 decreased antibody level in blood 55 31 hallmark (90%) Very frequent (99-80%) HP:0004313
11 depressed nasal bridge 55 31 hallmark (90%) Very frequent (99-80%) HP:0005280
12 abnormality of dental morphology 55 31 hallmark (90%) Very frequent (99-80%) HP:0006482
13 external ear malformation 55 31 hallmark (90%) Very frequent (99-80%) HP:0008572
14 reduced number of teeth 55 31 hallmark (90%) Very frequent (99-80%) HP:0009804
15 increased number of teeth 55 31 hallmark (90%) Very frequent (99-80%) HP:0011069
16 flat face 55 31 hallmark (90%) Very frequent (99-80%) HP:0012368
17 lymphangioma 55 31 hallmark (90%) Very frequent (99-80%) HP:0100764
18 gingival overgrowth 55 31 frequent (33%) Frequent (79-30%) HP:0000212
19 epicanthus 55 31 frequent (33%) Frequent (79-30%) HP:0000286
20 broad forehead 55 31 frequent (33%) Frequent (79-30%) HP:0000337
21 glaucoma 55 31 frequent (33%) Frequent (79-30%) HP:0000501
22 narrow chest 55 31 frequent (33%) Frequent (79-30%) HP:0000774
23 erysipelas 55 31 frequent (33%) Frequent (79-30%) HP:0001055
24 seizures 55 31 frequent (33%) Frequent (79-30%) HP:0001250
25 ascites 55 31 frequent (33%) Frequent (79-30%) HP:0001541
26 splenomegaly 55 31 frequent (33%) Frequent (79-30%) HP:0001744
27 recurrent respiratory infections 55 31 frequent (33%) Frequent (79-30%) HP:0002205
28 lymphadenopathy 55 31 frequent (33%) Frequent (79-30%) HP:0002716
29 horseshoe kidney 55 31 occasional (7.5%) Occasional (29-5%) HP:0000085
30 ectopic kidney 55 31 occasional (7.5%) Occasional (29-5%) HP:0000086
31 narrow mouth 55 31 occasional (7.5%) Occasional (29-5%) HP:0000160
32 retrognathia 55 31 occasional (7.5%) Occasional (29-5%) HP:0000278
33 short philtrum 55 31 occasional (7.5%) Occasional (29-5%) HP:0000322
34 conductive hearing impairment 55 31 occasional (7.5%) Occasional (29-5%) HP:0000405
35 pachygyria 55 31 occasional (7.5%) Occasional (29-5%) HP:0001302
36 craniosynostosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0001363
37 pericardial effusion 55 31 occasional (7.5%) Occasional (29-5%) HP:0001698
38 abnormality of the foot 55 31 occasional (7.5%) Occasional (29-5%) HP:0001760
39 hydrops fetalis 55 31 occasional (7.5%) Occasional (29-5%) HP:0001789
40 pyloric stenosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0002021
41 respiratory insufficiency 55 31 occasional (7.5%) Occasional (29-5%) HP:0002093
42 sparse axillary hair 55 31 occasional (7.5%) Occasional (29-5%) HP:0002215
43 hypocalcemia 55 31 occasional (7.5%) Occasional (29-5%) HP:0002901
44 finger syndactyly 55 31 occasional (7.5%) Occasional (29-5%) HP:0006101
45 pulmonary lymphangiectasia 55 31 occasional (7.5%) Occasional (29-5%) HP:0006521
46 chylothorax 55 31 occasional (7.5%) Occasional (29-5%) HP:0010310
47 arteriovenous malformation 55 31 occasional (7.5%) Occasional (29-5%) HP:0100026
48 camptodactyly of finger 55 31 occasional (7.5%) Occasional (29-5%) HP:0100490
49 benign neoplasm of the central nervous system 55 31 occasional (7.5%) Occasional (29-5%) HP:0100835
50 abnormal facial shape 55 Very frequent (99-80%)

MGI Mouse Phenotypes related to Hennekam Syndrome:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.87 ADAMTS3 DCHS1 FAT4 FLT4 KITLG PROX1
2 digestive/alimentary MP:0005381 9.86 ADAMTS3 ALB DCHS1 EGF FAT4 FLT4
3 immune system MP:0005387 9.76 ADAMTS3 CCBE1 CDH17 EGF FLT4 KITLG
4 liver/biliary system MP:0005370 9.43 KITLG PROX1 ADAMTS3 ALB CCBE1 FLT4
5 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:

38
Skin, Eye, Kidney

Publications for Hennekam Syndrome

Articles related to Hennekam Syndrome:

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

Variations for Hennekam Syndrome

ClinVar genetic disease variations for Hennekam Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 CCBE1 NM_133459.3(CCBE1): c.223T> A (p.Cys75Ser) single nucleotide variant Pathogenic rs121908250 GRCh37 Chromosome 18, 57147460: 57147460
2 CCBE1 NM_133459.3(CCBE1): c.305G> C (p.Cys102Ser) single nucleotide variant Pathogenic rs121908251 GRCh37 Chromosome 18, 57136800: 57136800
3 CCBE1 NM_133459.3(CCBE1): c.979G> C (p.Gly327Arg) single nucleotide variant Pathogenic rs121908252 GRCh37 Chromosome 18, 57105351: 57105351
4 CCBE1 NM_133459.3(CCBE1): c.683_684insT (p.Leu229Profs) insertion Pathogenic rs563023244 GRCh38 Chromosome 18, 59448074: 59448075
5 CCBE1 NM_133459.3(CCBE1): c.520T> C (p.Cys174Arg) single nucleotide variant Pathogenic rs121908254 GRCh37 Chromosome 18, 57134004: 57134004

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 14)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.78 CDH17 DCHS1 EGF FLT4 KITLG VEGFC
2 12.56 EGF FLT4 KITLG VEGFC
3 12.46 EGF FLT4 KITLG VEGFC
4
Show member pathways
12.4 EGF FLT4 KITLG VEGFC
5
Show member pathways
12.32 EGF FLT4 KITLG VEGFC
6
Show member pathways
12.07 EGF FLT4 VEGFC
7 11.59 CDH17 DCHS1 EGF
8 11.44 FLT4 PROX1 VEGFC
9 11.42 EGF FLT4 KITLG VEGFC
10 11.15 ALB EGF KITLG PROX1 SERPINA1
11 10.97 DCHS1 FAT4
12 10.84 FLT4 VEGFC
13
Show member pathways
10.57 FLT4 VEGFC
14 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 9.76 ADAMTS2 ADAMTS3 ALB CCBE1 EGF KITLG
2 extracellular region GO:0005576 9.61 ADAMTS2 ADAMTS3 ALB CCBE1 EGF FLT4
3 proteinaceous extracellular matrix GO:0005578 9.56 ADAMTS2 ADAMTS3 CCBE1 SERPINA1
4 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 24)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of cell proliferation GO:0008284 9.83 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 9.74 DCHS1 FAT4 PROX1
4 lung development GO:0030324 9.72 ADAMTS2 CCBE1 PROX1
5 positive regulation of peptidyl-tyrosine phosphorylation GO:0050731 9.71 EGF KITLG VEGFC
6 positive regulation of endothelial cell proliferation GO:0001938 9.67 FLT4 PROX1 VEGFC
7 respiratory gaseous exchange GO:0007585 9.62 CCBE1 FLT4
8 digestive tract development GO:0048565 9.61 DCHS1 FAT4
9 calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules GO:0016339 9.61 CDH17 DCHS1
10 hippo signaling GO:0035329 9.6 DCHS1 FAT4
11 positive regulation of vascular endothelial growth factor production GO:0010575 9.59 CCBE1 FLT4
12 sprouting angiogenesis GO:0002040 9.58 CCBE1 FLT4
13 respiratory system process GO:0003016 9.56 CCBE1 FLT4
14 positive regulation of endothelial cell migration GO:0010595 9.54 CCBE1 FLT4 PROX1
15 embryonic retina morphogenesis in camera-type eye GO:0060059 9.52 EGF PROX1
16 nephron development GO:0072006 9.51 DCHS1 FAT4
17 venous blood vessel morphogenesis GO:0048845 9.48 CCBE1 PROX1
18 ossification involved in bone maturation GO:0043931 9.46 DCHS1 FAT4
19 platelet degranulation GO:0002576 9.46 ALB EGF SERPINA1 VEGFC
20 positive regulation of vascular endothelial growth factor signaling pathway GO:1900748 9.4 ADAMTS3 CCBE1
21 condensed mesenchymal cell proliferation GO:0072137 9.32 DCHS1 FAT4
22 positive regulation of lymphangiogenesis GO:1901492 9.26 CCBE1 VEGFC
23 lymph vessel development GO:0001945 9.13 CCBE1 FLT4 PROX1
24 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

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10 dbSNP
11 DGIdb
16 ExPASy
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