MCID: HNN005
MIFTS: 45

Hennekam Lymphangiectasia-Lymphedema Syndrome 1 malady

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

Aliases & Classifications for Hennekam Lymphangiectasia-Lymphedema Syndrome 1

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Aliases & Descriptions for Hennekam Lymphangiectasia-Lymphedema Syndrome 1:

Name: Hennekam Lymphangiectasia-Lymphedema Syndrome 1 52 70 68
Hennekam Syndrome 11 48 25 54 70 13
Hennekam Lymphangiectasia-Lymphedema Syndrome 11 24 25 12
Hennekam Lymphangiectasia Lymphedema Syndrome 48 27 39 68
Lymphedema-Lymphangiectasia-Intellectual Disability Syndrome 25 54
Generalized Lymphatic Dysplasia 25 70
Intestinal Lymphagiectasia Lymphedema Intellectual Deficit Syndrome 48
 
Intestinal Lymphagiectasia-Lymphedema-Mental Retardation Syndrome 25
Lymphedem-Lymphangiectasia-Intellectual Disability Syndrome 11
Lymphedema-Lymphangiectasia-Mental Retardation Syndrome 70
Lymphangiectasies and Lymphedema Hennekam Type 48
Lymphangiectasis, Intestinal 39
Hklls1 70

Characteristics:

Orphanet epidemiological data:

54
hennekam syndrome:
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood

HPO:

64
hennekam lymphangiectasia-lymphedema syndrome 1:
Inheritance: autosomal recessive inheritance

Classifications:



External Ids:

OMIM52 235510
Disease Ontology11 DOID:0060366
Orphanet54 ORPHA2136
SNOMED-CT62 234146006
UMLS via Orphanet69 C0340834
ICD10 via Orphanet31 Q87.8
MedGen37 C0340834

Summaries for Hennekam Lymphangiectasia-Lymphedema Syndrome 1

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NIH Rare Diseases:48 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 Lymphangiectasia-Lymphedema Syndrome 1, also known as hennekam syndrome, is related to hennekam lymphangiectasia-lymphedema syndrome 2 and ausems wittebol-post hennekam syndrome, and has symptoms including malar flattening, hypertelorism and low-set, posteriorly rotated ears. An important gene associated with Hennekam Lymphangiectasia-Lymphedema Syndrome 1 is CCBE1 (Collagen And Calcium Binding EGF Domains 1), and among its related pathways are VEGFR3 signaling in lymphatic endothelium and VEGF binds to VEGFR leading to receptor dimerization. Affiliated tissues include kidney, skin and thyroid, and related mouse phenotypes are immune system and digestive/alimentary.

Disease Ontology:11 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.

UniProtKB/Swiss-Prot:70 Hennekam lymphangiectasia-lymphedema syndrome 1: A generalized lymph-vessels dysplasia characterized by intestinal lymphangiectasia with severe lymphedema of the limbs, genitalia and face. In addition, affected individuals have unusual facies and severe mental retardation.

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.

OMIM:52 Hennekam lymphangiectasia-lymphedema syndrome is an autosomal recessive disorder characterized by generalized lymphatic... (235510) more...

Wikipedia:71 Hennekam syndrome also known as Hennekam lymphangiectasia–lymphedema syndrome and intestinal... more...

Related Diseases for Hennekam Lymphangiectasia-Lymphedema Syndrome 1

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Diseases in the Hennekam Lymphangiectasia-Lymphedema Syndrome 1 family:

Hennekam Lymphangiectasia-Lymphedema Syndrome 2

Diseases related to Hennekam Lymphangiectasia-Lymphedema Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 40)
idRelated DiseaseScoreTop Affiliating Genes
1hennekam lymphangiectasia-lymphedema syndrome 212.7
2ausems wittebol-post hennekam syndrome11.8
3lymphangiectasia, intestinal11.0
4cleft lip-retinopathy syndrome10.9
5synpolydactyly10.4CCBE1, FAT4
6diamond-blackfan anemia 410.3ALB, CCBE1
7lymphocytes absent10.3FLT4, PROX1
8silicosiderosis10.3FLT4, PROX1
9calcaneonavicular coalition10.3FLT4, VEGFC
10congenital cystic eye multiple ocular and intracranial anomalies10.3FLT4, PROX1
11hyperlucent lung10.2FLT4, PROX1
12epidermolysis bullosa10.2FLT4, PROX1
13ocular melanoma10.2FLT4, PROX1
14pediatric infratentorial ependymoma10.1FLT4, VEGFC
15polysyndactyly with cardiac malformation10.1ALB, SERPINA1
16horner's syndrome10.1ALB, SERPINA1
17chikungunya10.1FLT4, PROX1
18hyperuricemia10.1ALB, SERPINA1
19duodenal disease10.1ALB, SERPINA1
20lymphedema10.1
21sweat gland cancer10.0ALB, SERPINA1
22contagious pustular dermatitis10.0ALB, SERPINA1
23central nervous system adult germ cell tumor10.0ALB, SERPINA1
24leydig cell tumor10.0FLT4, PROX1, VEGFC
25hepatic coma9.9ALB, SERPINA1
26acute liver failure9.9ALB, EGF
27intracranial hemorrhage in brain cerebrovascular malformations9.9FLT4, PROX1, VEGFC
28carbohydrate metabolic disorder9.9EGF, FAT4
29acute gonococcal cervicitis9.9ALB, CCBE1, SERPINA1
30pericoronitis9.8KITLG, SERPINA1
31laryngeal tuberculosis9.8ALB, SERPINA1
32craniosynostosis9.8
33van maldergem syndrome9.8
34cerebritis9.8
35hydrops fetalis9.8
36pulpitis9.8ALB, EGF
37lymphopenia9.7ALB, SERPINA1
38eczematous dermatitis of eyelid9.5ALB, SERPINA1
39lymphoid leukemia9.4CCBE1, FAT4, FLT4, PROX1, VEGFC
40orofaciodigital syndrome vii7.3ALB, CCBE1, EGF, FAT4, FLT4, KITLG

Graphical network of the top 20 diseases related to Hennekam Lymphangiectasia-Lymphedema Syndrome 1:



Diseases related to hennekam lymphangiectasia-lymphedema syndrome 1

Symptoms & Phenotypes for Hennekam Lymphangiectasia-Lymphedema Syndrome 1

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Symptoms by clinical synopsis from OMIM:

235510

Clinical features from OMIM:

235510

Human phenotypes related to Hennekam Lymphangiectasia-Lymphedema Syndrome 1:

 64 (show all 92)
id Description HPO Frequency HPO Source Accession
1 malar flattening64 hallmark (90%) HP:0000272
2 hypertelorism64 hallmark (90%) HP:0000316
3 low-set, posteriorly rotated ears64 hallmark (90%) HP:0000368
4 delayed eruption of teeth64 hallmark (90%) HP:0000684
5 lymphedema64 hallmark (90%) HP:0001004
6 lymphopenia64 hallmark (90%) HP:0001888
7 abnormal facial shape64 hallmark (90%) HP:0001999
8 malabsorption64 hallmark (90%) HP:0002024
9 decreased antibody level in blood64 hallmark (90%) HP:0004313
10 depressed nasal bridge64 hallmark (90%) HP:0005280
11 abnormality of dental morphology64 hallmark (90%) HP:0006482
12 external ear malformation64 hallmark (90%) HP:0008572
13 reduced number of teeth64 hallmark (90%) HP:0009804
14 increased number of teeth64 hallmark (90%) HP:0011069
15 cognitive impairment64 hallmark (90%) HP:0100543
16 lymphangioma64 hallmark (90%) HP:0100764
17 abnormality of the genital system64 typical (50%) HP:0000078
18 gingival overgrowth64 typical (50%) HP:0000212
19 epicanthus64 typical (50%) HP:0000286
20 broad forehead64 typical (50%) HP:0000337
21 narrow chest64 typical (50%) HP:0000774
22 erysipelas64 typical (50%) HP:0001055
23 seizures64 typical (50%) HP:0001250
24 ascites64 typical (50%) HP:0001541
25 splenomegaly64 typical (50%) HP:0001744
26 recurrent respiratory infections64 typical (50%) HP:0002205
27 lymphadenopathy64 typical (50%) HP:0002716
28 narrow mouth64 occasional (7.5%) HP:0000160
29 short philtrum64 occasional (7.5%) HP:0000322
30 micrognathia64 occasional (7.5%) HP:0000347
31 conductive hearing impairment64 occasional (7.5%) HP:0000405
32 glaucoma64 occasional (7.5%) HP:0000501
33 craniosynostosis64 occasional (7.5%) HP:0001363
34 abnormality of the pericardium64 occasional (7.5%) HP:0001697
35 abnormality of the foot64 occasional (7.5%) HP:0001760
36 hydrops fetalis64 occasional (7.5%) HP:0001789
37 pyloric stenosis64 occasional (7.5%) HP:0002021
38 respiratory insufficiency64 occasional (7.5%) HP:0002093
39 abnormality of the pleura64 occasional (7.5%) HP:0002103
40 abnormality of neuronal migration64 occasional (7.5%) HP:0002269
41 hypocalcemia64 occasional (7.5%) HP:0002901
42 finger syndactyly64 occasional (7.5%) HP:0006101
43 arteriovenous malformation64 occasional (7.5%) HP:0100026
44 camptodactyly of finger64 occasional (7.5%) HP:0100490
45 abnormal localization of kidney64 occasional (7.5%) HP:0100542
46 benign neoplasm of the central nervous system64 occasional (7.5%) HP:0100835
47 cryptorchidism64 HP:0000028
48 vesicoureteral reflux64 HP:0000076
49 horseshoe kidney64 HP:0000085
50 ectopic kidney64 HP:0000086
51 hydronephrosis64 HP:0000126
52 narrow palate64 HP:0000189
53 retrognathia64 HP:0000278
54 smooth philtrum64 HP:0000319
55 low-set ears64 HP:0000369
56 sensorineural hearing impairment64 HP:0000407
57 wide nasal bridge64 HP:0000431
58 oligodontia64 HP:0000677
59 hyperactivity64 HP:0000752
60 pectus excavatum64 HP:0000767
61 hirsutism64 HP:0001007
62 intellectual disability64 HP:0001249
63 pachygyria64 HP:0001302
64 mild postnatal growth retardation64 HP:0001530
65 umbilical hernia64 HP:0001537
66 ventricular septal defect64 HP:0001629
67 atria septal defect64 HP:0001631
68 pericardial effusion64 HP:0001698
69 talipes equinovarus64 HP:0001762
70 short foot64 HP:0001773
71 rectal prolapse64 HP:0002035
72 pleural effusion64 HP:0002202
73 protein-losing enteropathy64 HP:0002243
74 intestinal lymphangiectasia64 HP:0002593
75 scoliosis64 HP:0002650
76 delayed skeletal maturation64 HP:0002750
77 hypoplastic iliac wing64 HP:0002866
78 hypoalbuminemia64 HP:0003073
79 spina bifida occulta64 HP:0003298
80 short palm64 HP:0004279
81 coronal craniosynostosis64 HP:0004440
82 pericardial lymphangiectasia64 HP:0005183
83 pleural lymphangiectasia64 HP:0006531
84 bilateral single transverse palmar creases64 HP:0007598
85 thyroid lymphangiectasia64 HP:0008229
86 joint contracture of the hand64 HP:0009473
87 cutaneous finger syndactyly64 HP:0010554
88 conical incisor64 HP:0011065
89 flat face64 HP:0012368
90 camptodactyly64 HP:0012385
91 periorbital edema64 HP:0100539
92 small hand64 HP:0200055

UMLS symptoms related to Hennekam Lymphangiectasia-Lymphedema Syndrome 1:


seizures, periorbital edema

MGI Mouse Phenotypes related to Hennekam Lymphangiectasia-Lymphedema Syndrome 1 according to GeneCards Suite gene sharing:

41
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053878.2CCBE1, EGF, FLT4, KITLG, PROX1, VEGFC
2MP:00053818.1ALB, EGF, FAT4, FLT4, KITLG, PROX1
3MP:00053707.9ALB, CCBE1, FLT4, KITLG, PROX1

Drugs & Therapeutics for Hennekam Lymphangiectasia-Lymphedema Syndrome 1

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Interventional clinical trials:

Search ClinicalTrials, NIH Clinical Center for Hennekam Lymphangiectasia-Lymphedema Syndrome 1


Cochrane evidence based reviews: lymphangiectasis, intestinal

Genetic Tests for Hennekam Lymphangiectasia-Lymphedema Syndrome 1

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Genetic tests related to Hennekam Lymphangiectasia-Lymphedema Syndrome 1:

id Genetic test Affiliating Genes
1 Hennekam Lymphangiectasia-Lymphedema Syndrome27 24 CCBE1

Anatomical Context for Hennekam Lymphangiectasia-Lymphedema Syndrome 1

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MalaCards organs/tissues related to Hennekam Lymphangiectasia-Lymphedema Syndrome 1:

36
Kidney, Skin, Thyroid

Publications for Hennekam Lymphangiectasia-Lymphedema Syndrome 1

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Variations for Hennekam Lymphangiectasia-Lymphedema Syndrome 1

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UniProtKB/Swiss-Prot genetic disease variations for Hennekam Lymphangiectasia-Lymphedema Syndrome 1:

70
id Symbol AA change Variation ID SNP ID
1CCBE1p.Cys75SerVAR_063746rs121908250
2CCBE1p.Cys102SerVAR_063747rs121908251
3CCBE1p.Arg158CysVAR_063748rs121908253
4CCBE1p.Cys174ArgVAR_063749rs121908254
5CCBE1p.Gly327ArgVAR_063750rs121908252

Clinvar genetic disease variations for Hennekam Lymphangiectasia-Lymphedema Syndrome 1:

5
id Gene Variation Type Significance SNP ID Assembly Location
1CCBE1NM_133459.3(CCBE1): c.223T> A (p.Cys75Ser)SNVPathogenicrs121908250GRCh37Chr 18, 57147460: 57147460
2CCBE1NM_133459.3(CCBE1): c.305G> C (p.Cys102Ser)SNVPathogenicrs121908251GRCh37Chr 18, 57136800: 57136800
3CCBE1NM_133459.3(CCBE1): c.979G> C (p.Gly327Arg)SNVPathogenicrs121908252GRCh37Chr 18, 57105351: 57105351
4CCBE1NM_133459.3(CCBE1): c.683_684insT (p.Leu229Profs)insertionPathogenicrs563023244GRCh38Chr 18, 59448074: 59448075
5CCBE1NM_133459.3(CCBE1): c.472C> T (p.Arg158Cys)SNVPathogenicrs121908253GRCh37Chr 18, 57134052: 57134052
6CCBE1NM_133459.3(CCBE1): c.520T> C (p.Cys174Arg)SNVPathogenicrs121908254GRCh37Chr 18, 57134004: 57134004

Expression for genes affiliated with Hennekam Lymphangiectasia-Lymphedema Syndrome 1

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Search GEO for disease gene expression data for Hennekam Lymphangiectasia-Lymphedema Syndrome 1.

Pathways for genes affiliated with Hennekam Lymphangiectasia-Lymphedema Syndrome 1

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Pathways related to Hennekam Lymphangiectasia-Lymphedema Syndrome 1 according to GeneCards Suite gene sharing:

(show all 15)
idSuper pathwaysScoreTop Affiliating Genes
19.7FLT4, VEGFC
2
Show member pathways
9.7FLT4, VEGFC
39.4EGF, FLT4
4
Show member pathways
9.2FLT4, PROX1, VEGFC
5
Show member pathways
9.1EGF, FLT4, VEGFC
69.1EGF, FLT4, VEGFC
78.7EGF, KITLG, VEGFC
8
Show member pathways
8.2EGF, FLT4, KITLG, VEGFC
9
Show member pathways
8.2EGF, FLT4, KITLG, VEGFC
108.2EGF, FLT4, KITLG, VEGFC
11
Show member pathways
8.2EGF, FLT4, KITLG, VEGFC
12
Show member pathways
8.2EGF, FLT4, KITLG, VEGFC
138.2EGF, FLT4, KITLG, VEGFC
14
Show member pathways
8.2EGF, FLT4, KITLG, VEGFC
157.5ALB, EGF, KITLG, PROX1, SERPINA1

GO Terms for genes affiliated with Hennekam Lymphangiectasia-Lymphedema Syndrome 1

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Cellular components related to Hennekam Lymphangiectasia-Lymphedema Syndrome 1 according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1platelet alpha granule lumenGO:00310938.4ALB, EGF, SERPINA1, VEGFC
2extracellular regionGO:00055767.9ALB, EGF, FLT4, KITLG, SERPINA1, VEGFC
3extracellular spaceGO:00056157.8ALB, CCBE1, EGF, KITLG, SERPINA1, VEGFC

Biological processes related to Hennekam Lymphangiectasia-Lymphedema Syndrome 1 according to GeneCards Suite gene sharing:

(show all 13)
idNameGO IDScoreTop Affiliating Genes
1positive regulation of lymphangiogenesisGO:190149210.4CCBE1, VEGFC
2lymph vessel developmentGO:000194510.3FLT4, PROX1
3positive regulation of vascular endothelial growth factor productionGO:001057510.3CCBE1, FLT4
4respiratory gaseous exchangeGO:000758510.2CCBE1, FLT4
5respiratory system processGO:000301610.2CCBE1, FLT4
6lymphangiogenesisGO:000194610.0CCBE1, FLT4, PROX1
7sprouting angiogenesisGO:00020409.9CCBE1, FLT4
8positive regulation of endothelial cell migrationGO:00105959.9CCBE1, FLT4, PROX1
9venous blood vessel morphogenesisGO:00488459.7CCBE1, PROX1
10positive regulation of MAP kinase activityGO:00434069.6EGF, KITLG
11positive regulation of peptidyl-tyrosine phosphorylationGO:00507319.2EGF, KITLG, VEGFC
12platelet degranulationGO:00025769.1ALB, EGF, SERPINA1, VEGFC
13positive regulation of cell proliferationGO:00082848.4EGF, FLT4, KITLG, PROX1, VEGFC

Molecular functions related to Hennekam Lymphangiectasia-Lymphedema Syndrome 1 according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1growth factor activityGO:00080839.1EGF, KITLG, VEGFC
2phosphatidylinositol-4,5-bisphosphate 3-kinase activityGO:00469349.0EGF, KITLG

Sources for Hennekam Lymphangiectasia-Lymphedema Syndrome 1

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
27GTR
28HGMD
29HMDB
30ICD10
31ICD10 via Orphanet
32ICD9CM
33IUPHAR
34KEGG
37MedGen
39MeSH
40MESH via Orphanet
41MGI
44NCI
45NCIt
46NDF-RT
49NINDS
50Novoseek
52OMIM
53OMIM via Orphanet
57PubMed
58QIAGEN
63SNOMED-CT via Orphanet
67Tumor Gene Family of Databases
68UMLS
69UMLS via Orphanet