HLTS
MCID: HYP139
MIFTS: 44

Hypotrichosis-Lymphedema-Telangiectasia Syndrome (HLTS)

Categories: Genetic diseases, Immune diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

MalaCards integrated aliases for Hypotrichosis-Lymphedema-Telangiectasia Syndrome:

Name: Hypotrichosis-Lymphedema-Telangiectasia Syndrome 57 12 20 72 36 29 13 6 15 39 70
Hlts 57 12 20 72
Hypotrichosis-Lymphedema-Telangiectasia-Membranoproliferative Glomerulonephritis Syndrome 20
Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome 20
Hypotrichosis Lymphedema Telangiectasia Syndrome 20

Characteristics:

OMIM®:

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

Miscellaneous:
two unrelated families have been reported (last curated june 2015)
skin and hair abnormalities apparent at birth
lymphedema occurs in the first or second decades of life (in most patients)


HPO:

31
hypotrichosis-lymphedema-telangiectasia syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

GARD : 20 Hypotrichosis-lymphedema-telangiectasia syndrome (HLTS) is a rare condition that, as the name suggests, is associated with sparse hair (hypotrichosis), lymphedema, and telangiectasia, particularly on the palms of the hands. Symptoms usually begin at birth or in early childhood and become worse over time. HLTS is thought to be caused by changes ( mutations ) in the SOX18 gene. It can follow both an autosomal dominant or an autosomal recessive pattern of inheritance, depending on the affected family. There is currently no cure for the condition. Treatment is based on the signs and symptoms present in each person.

MalaCards based summary : Hypotrichosis-Lymphedema-Telangiectasia Syndrome, also known as hlts, is related to hypotrichosis and hereditary lymphedema i. An important gene associated with Hypotrichosis-Lymphedema-Telangiectasia Syndrome is SOX18 (SRY-Box Transcription Factor 18), and among its related pathways/superpathways is Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers. Affiliated tissues include skin, heart and testis, and related phenotypes are abnormality of the dentition and alopecia

Disease Ontology : 12 A syndrome characterized by onset at birth or early childhood of progressive hypotrichosis, lymphedema, and telangiectasia that has material basis in homozygous or compound heterozygous mutation in SOX18 on chromosome 20q13.33.

OMIM® : 57 Hypotrichosis-lymphedema-telangiectasia syndrome is an autosomal recessive disorder characterized by these 3 features, which begin at birth or in early childhood and are progressive (summary by Irrthum et al., 2003). (607823) (Updated 05-Apr-2021)

KEGG : 36 Hypotrichosis-lymphedema-telangiectasia syndrome (HLTS) is an extremely rare lymphedema syndrome. The transcription factor SOX18 was shown to play a role in the development of hair, blood vessels and lymphatic vessels. SOX18 mutations are associated with both recessive and dominant HLTS.

UniProtKB/Swiss-Prot : 72 Hypotrichosis-lymphedema-telangiectasia syndrome: A syndrome characterized by absent eyebrows and eyelashes, lymphatic edemas of the inferior members or eyelids, and peripheral vein anomalies.

Related Diseases for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

Diseases related to Hypotrichosis-Lymphedema-Telangiectasia Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 36)
# Related Disease Score Top Affiliating Genes
1 hypotrichosis 30.8 TCEA2 SOX18 FOXC2 FLT4
2 hereditary lymphedema i 30.7 SOX18 PROX1 FOXC2 FLT4
3 hypotrichosis-lymphedema-telangiectasia-renal defect syndrome 30.5 TCEA2 SOX7 SOX18 SOX17
4 hereditary lymphedema 30.4 SOX18 FOXC2 FLT4
5 telangiectasis 10.5
6 yellow nail syndrome 10.2 SOX18 FOXC2
7 breast angiosarcoma 10.2 PROX1 FLT4
8 pulmonary hypertension 10.2
9 adams-oliver syndrome 10.2
10 congenital lymphedema 10.2 FOXC2 FLT4
11 kaposiform hemangioendothelioma 10.1 PROX1 FLT4
12 primary lymphedema 10.1 FOXC2 FLT4
13 acquired hemangioma 10.1 PROX1 LYVE1
14 cystic lymphangioma 10.1 PROX1 FOXC2
15 malignant ciliary body melanoma 10.1 PROX1 LYVE1
16 stork bite 10.1 PROX1 FLT4
17 ciliary body cancer 10.1 PROX1 LYVE1
18 intramuscular hemangioma 10.1 PROX1 LYVE1
19 hereditary lymphedema ii 10.1 SOX18 FOXC2 FLT4
20 lymphatic malformation 5 10.1 SOX18 FOXC2 FLT4
21 klippel-trenaunay-weber syndrome 10.1 SOX18 FOXC2 FLT4
22 gorham's disease 10.0 LYVE1 FLT4
23 capillary disease 10.0 PROX1 FLT4
24 inflammatory breast carcinoma 9.9 PROX1 LYVE1
25 capillary lymphangioma 9.9 PROX1 LYVE1 FLT4
26 lymphangioma 9.9 PROX1 LYVE1 FLT4
27 pyriform sinus cancer 9.9 LYVE1 FLT4
28 lymphangiosarcoma 9.9 PROX1 LYVE1 FLT4
29 lymphangitis 9.9 PROX1 LYVE1 FLT4
30 capillary hemangioma 9.9 PROX1 LYVE1 FLT4
31 hemangioma 9.9 PROX1 LYVE1 FLT4
32 ceroid lipofuscinosis, neuronal, 4b, autosomal dominant 9.9 SOX18 PRPF6 CHRNA4 ARFGAP3 ARFGAP1
33 diaphragm disease 9.8 SOX7 NR2F2
34 chylothorax, congenital 9.7 SOX18 PROX1 LYVE1 FOXC2 FLT4
35 lymphedema-distichiasis syndrome 9.7 SOX18 PROX1 LYVE1 FOXC2 FLT4
36 hennekam syndrome 9.7 SOX18 PROX1 LYVE1 FOXC2 FLT4

Graphical network of the top 20 diseases related to Hypotrichosis-Lymphedema-Telangiectasia Syndrome:



Diseases related to Hypotrichosis-Lymphedema-Telangiectasia Syndrome

Symptoms & Phenotypes for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

Human phenotypes related to Hypotrichosis-Lymphedema-Telangiectasia Syndrome:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 abnormality of the dentition 31 HP:0000164
2 alopecia 31 HP:0001596
3 palpebral edema 31 HP:0100540
4 absent eyelashes 31 HP:0000561
5 sparse hair 31 HP:0008070
6 thin skin 31 HP:0000963
7 absent eyebrow 31 HP:0002223
8 toenail dysplasia 31 HP:0100797
9 predominantly lower limb lymphedema 31 HP:0003550
10 nonimmune hydrops fetalis 31 HP:0001790
11 palmar telangiectasia 31 HP:0100869
12 hydrocele testis 31 HP:0000034

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skin Nails Hair Hair:
hypotrichosis
absent eyelashes
absent eyebrows
hair loss, progressive

Head And Neck Teeth:
normal teeth

Genitourinary External Genitalia Male:
hydrocele
scrotal edema

Skin Nails Hair Nails:
dysplastic toenails (in 1 patients)

Head And Neck Eyes:
absent eyelashes
absent eyebrows
eyelid edema (present at birth)

Skin Nails Hair Skin:
normal sweating
thin, transparent skin (hands and feet)
lower limb lymphedema
telangiectases (palms, soles, scalp, scrotum, legs)

Cardiovascular Heart:
dilation of the ascending aorta (in 1 patient)

Clinical features from OMIM®:

607823 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Hypotrichosis-Lymphedema-Telangiectasia Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.61 COL9A3 FLT4 FOXC2 LYVE1 NR2F2 PROX1
2 no phenotypic analysis MP:0003012 9.1 CHRNA4 FLT4 FOXC2 NR2F2 SOX17 SOX7

Drugs & Therapeutics for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Temporary Intra-operative Placement of HLT Percutaneous Aortic Valve Unknown status NCT00710775
2 HLT transfemOral Replacement of aortIc Valve Via transcatherteriZatiON Completed NCT02157142
3 Transfemoral Replacement of Aortic Valve With HLT MeriDIAN Valve Feasibility Trial CANADA Active, not recruiting NCT02838680
4 Transfemoral Replacement of Aortic Valve With HLT MeriDIAN Valve Early Feasibility Trial Active, not recruiting NCT02799823
5 Transfemoral Replacement of Aortic Valve With HLT MeriDIAN Valve CE Mark Trial Terminated NCT03805711
6 HLT transfemOral Replacement of aortIc Valve Via transcatherteriZatiON CANADA Withdrawn NCT02159794

Search NIH Clinical Center for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

Genetic Tests for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

Genetic tests related to Hypotrichosis-Lymphedema-Telangiectasia Syndrome:

# Genetic test Affiliating Genes
1 Hypotrichosis-Lymphedema-Telangiectasia Syndrome 29 SOX18

Anatomical Context for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

MalaCards organs/tissues related to Hypotrichosis-Lymphedema-Telangiectasia Syndrome:

40
Skin, Heart, Testis, Liver, Lung

Publications for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

Articles related to Hypotrichosis-Lymphedema-Telangiectasia Syndrome:

(show all 42)
# Title Authors PMID Year
1
Aortic Dilatation Associated With a De Novo Mutation in the SOX18 Gene: Expanding the Clinical Spectrum of Hypotrichosis-Lymphedema-Telangiectasia Syndrome. 57 61 6
26148450 2016
2
Hypotrichosis, lymphedema of the legs and acral telangiectasias--new syndrome? 6 57 61
11701398 2001
3
Mutations in the transcription factor gene SOX18 underlie recessive and dominant forms of hypotrichosis-lymphedema-telangiectasia. 6 57
12740761 2003
4
Hypotrichosis-lymphedema-telangiectasia-renal defect associated with a truncating mutation in the SOX18 gene. 6 61
24697860 2015
5
Vascular defects in a mouse model of hypotrichosis-lymphedema-telangiectasia syndrome indicate a role for SOX18 in blood vessel maturation. 61 57
19429912 2009
6
Not All Septal Defects Are Equal: Outcomes of Bilateral Lung Transplant With Cardiac Defect Repair vs Combined Heart-Lung Transplant in Patients With Eisenmenger Syndrome in the United States. 61
32565271 2020
7
Identification of aspartame-induced haematopoietic and lymphoid tumours in rats after lifetime treatment. 61
32622430 2020
8
Simultaneous Heart-Liver Transplantation for Congenital Heart Disease in the USA: Rapidly Increasing with Acceptable Outcomes. 61
32559317 2020
9
Pediatric heart-lung transplantation: A contemporary analysis of outcomes. 61
32067330 2020
10
A novel autosomal dominant mutation in SOX18 resulting in a fatal case of hypotrichosis-lymphedema-telangiectasia syndrome. 61
30549413 2018
11
Further delineation of the SOX18-related Hypotrichosis, Lymphedema, Telangiectasia syndrome (HTLS). 61
29307792 2018
12
Examining Mortality and Rejection in Combined Heart-Lung Transplantations. 61
28110488 2017
13
Building Language Resources for Exploring Autism Spectrum Disorders. 61
30167575 2016
14
A new method to diagnose discoid lateral menisci on radiographs. 61
26811036 2016
15
A novel SOX18 mutation uncovered in Jordanian patient with hypotrichosis-lymphedema-telangiectasia syndrome by Whole Exome Sequencing. 61
26631803 2016
16
Manual lateralization in macaques: handedness, target laterality and task complexity. 61
26292019 2016
17
Adverse events associated with incretin-based drugs in Japanese spontaneous reports: a mixed effects logistic regression model. 61
26989609 2016
18
Alteration of serum N-glycan profile in patients with autoimmune pancreatitis. 61
26723536 2016
19
Comparative Adjuvant Effects of Type II Heat-Labile Enterotoxins in Combination with Two Different Candidate Ricin Toxin Vaccine Antigens. 61
26491037 2015
20
Mismatch negativity in tobacco-naïve cannabis users and its alteration with acute nicotine administration. 61
26188167 2015
21
The Quest for an HIV-1 Vaccine Adjuvant: Bacterial Toxins as New Potential Platforms. 61
27375924 2014
22
Impact of congenital heart disease on outcomes of pediatric heart-lung transplantation. 61
24373099 2014
23
Intradermal administration of the Type II heat-labile enterotoxins LT-IIb and LT-IIc of enterotoxigenic Escherichia coli enhances humoral and CD8+ T cell immunity to a co-administered antigen. 61
25536061 2014
24
Type II heat-labile enterotoxins: structure, function, and immunomodulatory properties. 61
23137790 2013
25
Efficient SIVcpz replication in human lymphoid tissue requires viral matrix protein adaptation. 61
22505456 2012
26
Development and validation of a general health literacy test in Singapore. 61
21467097 2012
27
TLR2-dependent modulation of dendritic cells by LT-IIa-B5, a novel mucosal adjuvant derived from a type II heat-labile enterotoxin. 61
21791597 2011
28
CD9P-1 expression correlates with the metastatic status of lung cancer, and a truncated form of CD9P-1, GS-168AT2, inhibits in vivo tumour growth. 61
21206492 2011
29
LT-IIc, a new member of the type II heat-labile enterotoxin family encoded by an Escherichia coli strain obtained from a nonmammalian host. 61
20713622 2010
30
Influence of the MedDRA hierarchy on pharmacovigilance data mining results. 61
19230751 2009
31
A novel 9-amino-acid transactivation domain in the C-terminal part of Sox18. 61
17603017 2007
32
Genotype-phenotype correlations to aid in the prognosis of individuals with uncommon 20q13.33 subtelomere deletions: a collaborative study on behalf of the 'association des Cytogénéticiens de langue Française'. 61
17290276 2007
33
Outcome of heart-lung and bilateral sequential lung transplantation for cystic fibrosis: a UK national study. 61
15929949 2005
34
Heterotopic vs. orthotopic liver transplantation for chronic liver disease: a case-control comparison of short-term and long-term outcomes. 61
15776459 2005
35
Appraisal of the MedDRA conceptual structure for describing and grouping adverse drug reactions. 61
15649103 2005
36
A rabbit model for evaluation of surgical anesthesia and analgesia: characterization and validation with isoflurane anesthesia and fentanyl analgesia. 61
15549471 2004
37
An animal model for surgical anesthesia and analgesia: characterization with isoflurane anesthesia and remifentanil analgesia. 61
14570649 2003
38
Effects of coding dictionary on signal generation: a consideration of use of MedDRA compared with WHO-ART. 61
12071782 2002
39
Intravascular coagulation in liver transplantation--is it present or not? A comparison between orthotopic and heterotopic liver transplantation. 61
8446934 1993
40
New aspects of heterotopic liver transplantation. 61
1580985 1992
41
The perioperative use of blood components during heart and heart-lung transplantation. 61
1731437 1992
42
The pathology of combined heart-lung transplantation: an autopsy study. 61
3142814 1988

Variations for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

ClinVar genetic disease variations for Hypotrichosis-Lymphedema-Telangiectasia Syndrome:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SOX18 , TCEA2 NM_018419.3(SOX18):c.310G>C (p.Ala104Pro) SNV Pathogenic 8000 rs28936692 GRCh37: 20:62680560-62680560
GRCh38: 20:64049207-64049207
2 SOX18 , TCEA2 NM_018419.3(SOX18):c.283T>A (p.Trp95Arg) SNV Pathogenic 8001 rs28936693 GRCh37: 20:62680587-62680587
GRCh38: 20:64049234-64049234
3 SOX18 , TCEA2 NM_018419.3(SOX18):c.481C>T (p.Gln161Ter) SNV Pathogenic 162093 rs794728015 GRCh37: 20:62680193-62680193
GRCh38: 20:64048840-64048840

UniProtKB/Swiss-Prot genetic disease variations for Hypotrichosis-Lymphedema-Telangiectasia Syndrome:

72
# Symbol AA change Variation ID SNP ID
1 SOX18 p.Trp95Arg VAR_016210 rs28936693
2 SOX18 p.Ala104Pro VAR_016211 rs28936692

Expression for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

Search GEO for disease gene expression data for Hypotrichosis-Lymphedema-Telangiectasia Syndrome.

Pathways for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

Pathways related to Hypotrichosis-Lymphedema-Telangiectasia Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.92 SOX7 SOX17 PROX1

GO Terms for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

Cellular components related to Hypotrichosis-Lymphedema-Telangiectasia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin GO:0000785 9.1 SOX7 SOX18 SOX17 PROX1 NR2F2 FOXC2

Biological processes related to Hypotrichosis-Lymphedema-Telangiectasia Syndrome according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 10.07 TCEA2 SOX7 SOX18 SOX17 PROX1 NR2F2
2 positive regulation of transcription by RNA polymerase II GO:0045944 10 TCEA2 SOX18 SOX17 PRPF6 PROX1 NR2F2
3 positive regulation of transcription, DNA-templated GO:0045893 9.95 SOX7 SOX18 SOX17 NR2F2 FOXC2
4 positive regulation of endothelial cell migration GO:0010595 9.69 PROX1 FOXC2 FLT4
5 anatomical structure morphogenesis GO:0009653 9.65 SOX7 SOX18 SOX17 LYVE1 FOXC2
6 metanephros development GO:0001656 9.58 SOX17 FOXC2
7 blood vessel morphogenesis GO:0048514 9.58 NR2F2 FLT4
8 vasculature development GO:0001944 9.57 SOX18 FLT4
9 ventricular cardiac muscle tissue morphogenesis GO:0055010 9.56 PROX1 FOXC2
10 endoderm formation GO:0001706 9.54 SOX7 SOX17
11 embryonic heart tube development GO:0035050 9.5 SOX18 SOX17 FOXC2
12 regulation of stem cell proliferation GO:0072091 9.49 SOX18 SOX17
13 lymphatic endothelial cell differentiation GO:0060836 9.48 SOX18 PROX1
14 endocardial cell differentiation GO:0060956 9.43 SOX18 SOX17
15 lymphatic endothelial cell fate commitment GO:0060838 9.4 PROX1 NR2F2
16 stem cell fate specification GO:0048866 9.37 SOX18 SOX17
17 endocardium formation GO:0060214 9.33 SOX18 SOX17 PROX1
18 lymphangiogenesis GO:0001946 9.26 SOX18 PROX1 FOXC2 FLT4
19 lymph vessel development GO:0001945 9.02 SOX18 PROX1 NR2F2 FOXC2 FLT4

Molecular functions related to Hypotrichosis-Lymphedema-Telangiectasia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.73 SOX7 SOX18 SOX17 PROX1 NR2F2 FOXC2
2 DNA-binding transcription factor activity GO:0003700 9.63 SOX7 SOX18 SOX17 PROX1 NR2F2 FOXC2
3 transcription regulatory region sequence-specific DNA binding GO:0000976 9.35 SOX7 SOX18 SOX17 PROX1 FOXC2
4 sequence-specific DNA binding GO:0043565 9.1 SOX7 SOX18 SOX17 PROX1 NR2F2 FOXC2

Sources for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
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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