HKLLS2
MCID: HNN004
MIFTS: 23

Hennekam Lymphangiectasia-Lymphedema Syndrome 2 (HKLLS2)

Categories: Gastrointestinal diseases, Genetic diseases, Immune diseases

Aliases & Classifications for Hennekam Lymphangiectasia-Lymphedema Syndrome 2

MalaCards integrated aliases for Hennekam Lymphangiectasia-Lymphedema Syndrome 2:

Name: Hennekam Lymphangiectasia-Lymphedema Syndrome 2 57 72 29 6 70
Hklls2 57 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
hennekam lymphangiectasia-lymphedema syndrome 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hennekam Lymphangiectasia-Lymphedema Syndrome 2

UniProtKB/Swiss-Prot : 72 Hennekam lymphangiectasia-lymphedema syndrome 2: A form of Hennekam lymphangiectasia-lymphedema syndrome, 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 some manifest mental retardation. HKLLS2 individuals have lymphangiectasia variably affecting the gut, pericardium, lungs, kidneys, and genitalia. Other features include camptodactyly and rare syndactyly. HKLLS2 inheritance is autosomal recessive.

MalaCards based summary : Hennekam Lymphangiectasia-Lymphedema Syndrome 2, is also known as hklls2. An important gene associated with Hennekam Lymphangiectasia-Lymphedema Syndrome 2 is FAT4 (FAT Atypical Cadherin 4). Related phenotypes are hearing impairment and depressed nasal bridge

OMIM® : 57 Hennekam lymphangiectasia-lymphedema syndrome is an autosomal recessive disorder characterized by generalized lymphatic dysplasia affecting various organs, including the intestinal tract, pericardium, and limbs. Additional features of the disorder include facial dysmorphism and cognitive impairment (summary by Alders et al., 2014). For a discussion of genetic heterogeneity of Hennekam lymphangiectasia-lymphedema syndrome, see HKLLS1 (235510). (616006) (Updated 05-Apr-2021)

Related Diseases for Hennekam Lymphangiectasia-Lymphedema Syndrome 2

Diseases in the Hennekam Lymphangiectasia-Lymphedema Syndrome 1 family:

Hennekam Lymphangiectasia-Lymphedema Syndrome 2 Hennekam Lymphangiectasia-Lymphedema Syndrome 3

Symptoms & Phenotypes for Hennekam Lymphangiectasia-Lymphedema Syndrome 2

Human phenotypes related to Hennekam Lymphangiectasia-Lymphedema Syndrome 2:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 hearing impairment 31 very rare (1%) HP:0000365
2 depressed nasal bridge 31 very rare (1%) HP:0005280
3 hypertelorism 31 very rare (1%) HP:0000316
4 microtia 31 very rare (1%) HP:0008551
5 intellectual disability, mild 31 very rare (1%) HP:0001256
6 osteoporosis 31 very rare (1%) HP:0000939
7 growth delay 31 very rare (1%) HP:0001510
8 epicanthus 31 very rare (1%) HP:0000286
9 narrow mouth 31 very rare (1%) HP:0000160
10 blepharophimosis 31 very rare (1%) HP:0000581
11 camptodactyly 31 very rare (1%) HP:0012385
12 syndactyly 31 very rare (1%) HP:0001159
13 irregular dentition 31 very rare (1%) HP:0040079
14 intestinal lymphangiectasia 31 very rare (1%) HP:0002593
15 lymphedema 31 HP:0001004
16 flat face 31 HP:0012368
17 pulmonary lymphangiectasia 31 HP:0006521
18 pericardial lymphangiectasia 31 HP:0005183

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
hypertelorism
epicanthus
blepharophimosis

Head And Neck Face:
flat face
dysmorphic facies

Head And Neck Teeth:
irregular dentition

Abdomen Gastrointestinal:
intestinal lymphangiectasia

Growth Other:
growth retardation

Head And Neck Mouth:
small mouth

Genitourinary Kidneys:
renal lymphangiectasia

Muscle Soft Tissue:
lymphedema
lymphangiectasia

Skeletal Hands:
camptodactyly

Respiratory Lung:
pulmonary lymphangiectasia

Cardiovascular Heart:
pericardial lymphangiectasia

Head And Neck Ears:
small ears
hearing loss (in some patients)
thick helices

Head And Neck Nose:
flat nasal bridge

Neurologic Central Nervous System:
impaired cognition (in some patients)

Clinical features from OMIM®:

616006 (Updated 05-Apr-2021)

Drugs & Therapeutics for Hennekam Lymphangiectasia-Lymphedema Syndrome 2

Search Clinical Trials , NIH Clinical Center for Hennekam Lymphangiectasia-Lymphedema Syndrome 2

Genetic Tests for Hennekam Lymphangiectasia-Lymphedema Syndrome 2

Genetic tests related to Hennekam Lymphangiectasia-Lymphedema Syndrome 2:

# Genetic test Affiliating Genes
1 Hennekam Lymphangiectasia-Lymphedema Syndrome 2 29 FAT4

Anatomical Context for Hennekam Lymphangiectasia-Lymphedema Syndrome 2

Publications for Hennekam Lymphangiectasia-Lymphedema Syndrome 2

Articles related to Hennekam Lymphangiectasia-Lymphedema Syndrome 2:

# Title Authors PMID Year
1
Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome. 57 6
24913602 2014
2
Further delineation of Hennekam syndrome. 57 6
14564208 2003
3
Autosomal recessive intestinal lymphangiectasia and lymphedema, with facial anomalies and mental retardation. 6 57
2624276 1989
4
Mutations in genes encoding the cadherin receptor-ligand pair DCHS1 and FAT4 disrupt cerebral cortical development. 6
24056717 2013
5
Van Maldergem syndrome: further characterisation and evidence for neuronal migration abnormalities and autosomal recessive inheritance. 6
22473091 2012
6
An additional case of Hennekam lymphangiectasia-lymphedema syndrome caused by loss-of-function mutation in ADAMTS3. 61
30450763 2018

Variations for Hennekam Lymphangiectasia-Lymphedema Syndrome 2

ClinVar genetic disease variations for Hennekam Lymphangiectasia-Lymphedema Syndrome 2:

6 (show all 19)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FAT4 NM_024582.4(FAT4):c.7123G>A (p.Glu2375Lys) SNV Pathogenic 89006 rs398122955 GRCh37: 4:126355504-126355504
GRCh38: 4:125434349-125434349
2 FAT4 NM_001291285.1(FAT4):c.7035_7040TGGAAC[3] (p.2346_2347GT[3]) Microsatellite Pathogenic 156109 rs587777724 GRCh37: 4:126355413-126355414
GRCh38: 4:125434258-125434259
3 FAT4 NM_024582.4(FAT4):c.1195del (p.Leu399fs) Deletion Pathogenic 156110 rs587777725 GRCh37: 4:126238761-126238761
GRCh38: 4:125317606-125317606
4 FAT4 NM_024582.4(FAT4):c.12845C>T (p.Ser4282Phe) SNV Pathogenic 156111 rs199682210 GRCh37: 4:126408528-126408528
GRCh38: 4:125487373-125487373
5 FAT4 NM_024582.4(FAT4):c.7200-2A>C SNV Pathogenic 156112 rs587777726 GRCh37: 4:126367452-126367452
GRCh38: 4:125446297-125446297
6 FAT4 NM_001291303.3(FAT4):c.5944A>G (p.Ser1982Gly) SNV Uncertain significance 931780 GRCh37: 4:126336062-126336062
GRCh38: 4:125414907-125414907
7 FAT4 NM_001291303.3(FAT4):c.14404C>T (p.Pro4802Ser) SNV Uncertain significance 932020 GRCh37: 4:126412375-126412375
GRCh38: 4:125491220-125491220
8 FAT4 NM_024582.4(FAT4):c.5275A>G (p.Ile1759Val) SNV Uncertain significance 376888 rs145639192 GRCh37: 4:126320038-126320038
GRCh38: 4:125398883-125398883
9 FAT4 NM_001291303.3(FAT4):c.11706T>G (p.Asp3902Glu) SNV Uncertain significance 1028317 GRCh37: 4:126373871-126373871
GRCh38: 4:125452716-125452716
10 FAT4 NM_001291303.3(FAT4):c.2290G>A (p.Val764Ile) SNV Uncertain significance 1028320 GRCh37: 4:126239856-126239856
GRCh38: 4:125318701-125318701
11 FAT4 NM_001291303.3(FAT4):c.4432A>G (p.Ile1478Val) SNV Uncertain significance 1028321 GRCh37: 4:126241998-126241998
GRCh38: 4:125320843-125320843
12 FAT4 NM_001291303.3(FAT4):c.8753A>G (p.Glu2918Gly) SNV Uncertain significance 1028322 GRCh37: 4:126370918-126370918
GRCh38: 4:125449763-125449763
13 FAT4 NM_001291303.3(FAT4):c.9152C>A (p.Ser3051Tyr) SNV Uncertain significance 1028323 GRCh37: 4:126371317-126371317
GRCh38: 4:125450162-125450162
14 FAT4 NM_001291303.3(FAT4):c.12085G>A (p.Ala4029Thr) SNV Uncertain significance 1031381 GRCh37: 4:126389846-126389846
GRCh38: 4:125468691-125468691
15 FAT4 NM_024582.4(FAT4):c.12641G>A (p.Arg4214His) SNV Uncertain significance 432221 rs148170326 GRCh37: 4:126402718-126402718
GRCh38: 4:125481563-125481563
16 FAT4 NM_001291303.3(FAT4):c.5161A>G (p.Thr1721Ala) SNV Uncertain significance 1031382 GRCh37: 4:126242727-126242727
GRCh38: 4:125321572-125321572
17 FAT4 NM_001291303.3(FAT4):c.6515A>C (p.Asp2172Ala) SNV Uncertain significance 1031383 GRCh37: 4:126336633-126336633
GRCh38: 4:125415478-125415478
18 FAT4 NM_024582.4(FAT4):c.7103C>A (p.Ala2368Glu) SNV Uncertain significance 424428 rs116568645 GRCh37: 4:126355484-126355484
GRCh38: 4:125434329-125434329
19 FAT4 NM_001291303.3(FAT4):c.8313T>C (p.Asn2771=) SNV Uncertain significance 1032176 GRCh37: 4:126370478-126370478
GRCh38: 4:125449323-125449323

UniProtKB/Swiss-Prot genetic disease variations for Hennekam Lymphangiectasia-Lymphedema Syndrome 2:

72
# Symbol AA change Variation ID SNP ID
1 FAT4 p.Glu2375Lys VAR_070925 rs398122955
2 FAT4 p.Phe475Leu VAR_071948
3 FAT4 p.Glu486Gln VAR_071949
4 FAT4 p.Ser4282Phe VAR_071950 rs199682210

Expression for Hennekam Lymphangiectasia-Lymphedema Syndrome 2

Search GEO for disease gene expression data for Hennekam Lymphangiectasia-Lymphedema Syndrome 2.

Pathways for Hennekam Lymphangiectasia-Lymphedema Syndrome 2

GO Terms for Hennekam Lymphangiectasia-Lymphedema Syndrome 2

Sources for Hennekam Lymphangiectasia-Lymphedema Syndrome 2

3 CDC
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9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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28 GO
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30 HMDB
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33 ICD10 via Orphanet
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45 MESH via Orphanet
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49 NCI
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56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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