HLTS
MCID: HYP139
MIFTS: 43

Hypotrichosis-Lymphedema-Telangiectasia Syndrome (HLTS)

Categories: Genetic diseases, Immune diseases, Nephrological diseases, Rare diseases
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Aliases & Classifications for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

MalaCards integrated aliases for Hypotrichosis-Lymphedema-Telangiectasia Syndrome:

Name: Hypotrichosis-Lymphedema-Telangiectasia Syndrome 57 11 19 73 28 12 5 43 14 38 71 75
Hlts 57 11 19 73
Hypotrichosis-Lymphedema-Telangiectasia-Membranoproliferative Glomerulonephritis Syndrome 19
Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome 19
Hypotrichosis Lymphedema Telangiectasia Syndrome 19

Characteristics:


Inheritance:

Autosomal recessive 57

OMIM®:

57 (Updated 08-Dec-2022)
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)


Classifications:



Summaries for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

GARD: 19 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 in the SOX18 gene. It can follow both an autosomal dominant or an autosomal recessive pattern of inheritance, depending on the affected family.

MalaCards based summary: Hypotrichosis-Lymphedema-Telangiectasia Syndrome, also known as hlts, is related to hypotrichosis and hypotrichosis-lymphedema-telangiectasia-renal defect syndrome. An important gene associated with Hypotrichosis-Lymphedema-Telangiectasia Syndrome is SOX18 (SRY-Box Transcription Factor 18), and among its related pathways/superpathways are Embryonic and Induced Pluripotent Stem Cells and Lineage-specific Markers and Deactivation of the beta-catenin transactivating complex. Affiliated tissues include skin, testis and heart, and related phenotypes are abnormality of the dentition and alopecia

Disease Ontology: 11 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 08-Dec-2022)

UniProtKB/Swiss-Prot: 73 A syndrome characterized by absent eyebrows and eyelashes, lymphatic edemas of the inferior members or eyelids, and peripheral vein anomalies.

Wikipedia: 75 Hypotrichosis-lymphedema-telangiectasia syndrome is a congenital syndrome characterized by lymphedema... more...

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 34)
# Related Disease Score Top Affiliating Genes
1 hypotrichosis 30.7 SOX18 FOXC2 FLT4
2 hypotrichosis-lymphedema-telangiectasia-renal defect syndrome 30.4 SOX7 SOX18
3 lymphatic malformation 1 30.2 GJC2 FLT4
4 hereditary lymphedema i 29.3 SOX18 PROX1 NR2F2 ITGA9 GJC2 FOXC2
5 hereditary lymphedema 28.9 SOX18 PROX1 ITGA9 GJC2 FOXC2 FLT4
6 hypotrichosis 7 10.6
7 telangiectasis 10.6
8 contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a 10.2
9 pulmonary hypertension 10.2
10 alopecia 10.2
11 hydrocele 10.2
12 alopecia totalis 10.2
13 lutembacher's syndrome 10.1 SOX18 CALCRL
14 ceroid lipofuscinosis, neuronal, 4 10.0 SOX18 ARFGAP3 ARFGAP1
15 noonan syndrome 5 10.0 SOX18 GJC2
16 generalized lymphatic anomaly 10.0 PROX1 FLT4
17 lymphangiosarcoma 10.0 PROX1 FLT4
18 gorham's disease 10.0 PROX1 FLT4
19 capillary lymphangioma 10.0 PROX1 FLT4
20 congenital lymphedema 10.0 FOXC2 FLT4
21 hereditary lymphedema ii 9.9 SOX18 GJC2 FOXC2
22 yellow nail syndrome 9.9 SOX18 ITGA9 FOXC2
23 capillary hemangioma 9.9 PROX1 FLT4
24 leopard syndrome 2 9.9 SOX18 GJC2 CALCRL
25 lymphatic malformation 5 9.9 SOX18 FOXC2 FLT4
26 hypersensitivity reaction type iv disease 9.8 ARFGAP3 ARFGAP1
27 cystic lymphangioma 9.8 PROX1 FOXC2 FLT4
28 hereditary lymphedema ia 9.8 ITGA9 GJC2 FLT4
29 klippel-trenaunay-weber syndrome 9.7 SOX18 PROX1 FOXC2 FLT4
30 diaphragm disease 9.7 SOX7 NR2F2
31 chylothorax, congenital 9.5 SOX18 ITGA9 GJC2 FOXC2 FLT4
32 primary lymphedema 9.4 SOX18 GJC2 FOXC2 FLT4 CALCRL
33 lymphedema-distichiasis syndrome 9.3 SOX18 PROX1 ITGA9 GJC2 FOXC2 FLT4
34 hennekam syndrome 9.3 SOX18 PROX1 ITGA9 GJC2 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:

30 (show all 12)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of the dentition 30 HP:0000164
2 alopecia 30 HP:0001596
3 palpebral edema 30 HP:0100540
4 absent eyelashes 30 HP:0000561
5 sparse hair 30 HP:0008070
6 thin skin 30 HP:0000963
7 absent eyebrow 30 HP:0002223
8 toenail dysplasia 30 HP:0100797
9 predominantly lower limb lymphedema 30 HP:0003550
10 palmar telangiectasia 30 HP:0100869
11 hydrocele testis 30 HP:0000034
12 nonimmune hydrops fetalis 30 HP:0001790

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
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 08-Dec-2022)

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

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.02 CALCRL CHRNA4 FLT4 FOXC2 ITGA9 NR2F2
2 normal MP:0002873 9.98 FLT4 FOXC2 GJC2 ITGA9 PROX1 SOX17
3 no phenotypic analysis MP:0003012 9.95 CHRNA4 FLT4 FOXC2 ITGA9 NR2F2 SOX17
4 muscle MP:0005369 9.91 CALCRL FLT4 FOXC2 NR2F2 PROX1 SOX17
5 cardiovascular system MP:0005385 9.81 CALCRL FLT4 FOXC2 ITGA9 NR2F2 PROX1
6 digestive/alimentary MP:0005381 9.8 CALCRL FLT4 FOXC2 NR2F2 PROX1 SOX17
7 immune system MP:0005387 9.65 CALCRL CHRNA4 FLT4 FOXC2 GJC2 ITGA9
8 mortality/aging MP:0010768 9.36 CALCRL CHRNA4 FLT4 FOXC2 GJC2 ITGA9

Drugs & Therapeutics for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

Search Clinical Trials, NIH Clinical Center for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

Cochrane evidence based reviews: 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 28 SOX18

Anatomical Context for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

Organs/tissues related to Hypotrichosis-Lymphedema-Telangiectasia Syndrome:

MalaCards : Skin, Testis, Heart, Lung, Liver

Publications for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

Articles related to Hypotrichosis-Lymphedema-Telangiectasia Syndrome:

(show all 50)
# 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. 62 57 5
26148450 2016
2
Hypotrichosis, lymphedema of the legs and acral telangiectasias--new syndrome? 62 57 5
11701398 2001
3
Mutations in the transcription factor gene SOX18 underlie recessive and dominant forms of hypotrichosis-lymphedema-telangiectasia. 57 5
12740761 2003
4
Hypotrichosis-lymphedema-telangiectasia-renal defect associated with a truncating mutation in the SOX18 gene. 62 5
24697860 2015
5
Vascular defects in a mouse model of hypotrichosis-lymphedema-telangiectasia syndrome indicate a role for SOX18 in blood vessel maturation. 62 57
19429912 2009
6
Expanding the clinical spectrum of SOX18-related Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome. 62
36096470 2022
7
A Case with Hypotrichosis-Lymphedema-Telangiectasia Syndrome with Hair Shaft Fragility. 62
36407647 2022
8
Evaluation of tibial eminence morphology using magnetic resonance imaging (MRI) in juvenile patients with complete discoid lateral meniscus. 62
36443796 2022
9
Evolving Indications for Heart-Lung Transplant in Spain. 62
36319494 2022
10
A dominant-negative SOX18 mutant disrupts multiple regulatory layers essential to transcription factor activity. 62
34570228 2021
11
Immunomodulatory regulation by heat-labile enterotoxins and potential therapeutic applications. 62
34148503 2021
12
Hypotrichosis-lymphedema-telangiectasia syndrome: Report of ileal atresia associated with a SOX18 de novo pathogenic variant and review of the phenotypic spectrum. 62
33851505 2021
13
Simultaneous Heart-Liver Transplantation for Congenital Heart Disease in the United States: Rapidly Increasing With Acceptable Outcomes. 62
32559317 2021
14
Aspartame and cancer - new evidence for causation. 62
33845854 2021
15
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. 62
32565271 2020
16
Identification of aspartame-induced haematopoietic and lymphoid tumours in rats after lifetime treatment. 62
32622430 2020
17
Pediatric heart-lung transplantation: A contemporary analysis of outcomes. 62
32067330 2020
18
A novel autosomal dominant mutation in SOX18 resulting in a fatal case of hypotrichosis-lymphedema-telangiectasia syndrome. 62
30549413 2018
19
Further delineation of the SOX18-related Hypotrichosis, Lymphedema, Telangiectasia syndrome (HTLS). 62
29307792 2018
20
Examining Mortality and Rejection in Combined Heart-Lung Transplantations. 62
28110488 2017
21
Building Language Resources for Exploring Autism Spectrum Disorders. 62
30167575 2016
22
A new method to diagnose discoid lateral menisci on radiographs. 62
26811036 2016
23
A novel SOX18 mutation uncovered in Jordanian patient with hypotrichosis-lymphedema-telangiectasia syndrome by Whole Exome Sequencing. 62
26631803 2016
24
Manual lateralization in macaques: handedness, target laterality and task complexity. 62
26292019 2016
25
Alteration of serum N-glycan profile in patients with autoimmune pancreatitis. 62
26723536 2016
26
Adverse events associated with incretin-based drugs in Japanese spontaneous reports: a mixed effects logistic regression model. 62
26989609 2016
27
Comparative Adjuvant Effects of Type II Heat-Labile Enterotoxins in Combination with Two Different Candidate Ricin Toxin Vaccine Antigens. 62
26491037 2015
28
Mismatch negativity in tobacco-naïve cannabis users and its alteration with acute nicotine administration. 62
26188167 2015
29
The Quest for an HIV-1 Vaccine Adjuvant: Bacterial Toxins as New Potential Platforms. 62
27375924 2014
30
Impact of congenital heart disease on outcomes of pediatric heart-lung transplantation. 62
24373099 2014
31
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. 62
25536061 2014
32
Type II heat-labile enterotoxins: structure, function, and immunomodulatory properties. 62
23137790 2013
33
Efficient SIVcpz replication in human lymphoid tissue requires viral matrix protein adaptation. 62
22505456 2012
34
Development and validation of a general health literacy test in Singapore. 62
21467097 2012
35
TLR2-dependent modulation of dendritic cells by LT-IIa-B5, a novel mucosal adjuvant derived from a type II heat-labile enterotoxin. 62
21791597 2011
36
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. 62
21206492 2011
37
LT-IIc, a new member of the type II heat-labile enterotoxin family encoded by an Escherichia coli strain obtained from a nonmammalian host. 62
20713622 2010
38
Influence of the MedDRA hierarchy on pharmacovigilance data mining results. 62
19230751 2009
39
A novel 9-amino-acid transactivation domain in the C-terminal part of Sox18. 62
17603017 2007
40
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'. 62
17290276 2007
41
Outcome of heart-lung and bilateral sequential lung transplantation for cystic fibrosis: a UK national study. 62
15929949 2005
42
Heterotopic vs. orthotopic liver transplantation for chronic liver disease: a case-control comparison of short-term and long-term outcomes. 62
15776459 2005
43
Appraisal of the MedDRA conceptual structure for describing and grouping adverse drug reactions. 62
15649103 2005
44
A rabbit model for evaluation of surgical anesthesia and analgesia: characterization and validation with isoflurane anesthesia and fentanyl analgesia. 62
15549471 2004
45
An animal model for surgical anesthesia and analgesia: characterization with isoflurane anesthesia and remifentanil analgesia. 62
14570649 2003
46
Effects of coding dictionary on signal generation: a consideration of use of MedDRA compared with WHO-ART. 62
12071782 2002
47
Intravascular coagulation in liver transplantation--is it present or not? A comparison between orthotopic and heterotopic liver transplantation. 62
8446934 1993
48
New aspects of heterotopic liver transplantation. 62
1580985 1992
49
The perioperative use of blood components during heart and heart-lung transplantation. 62
1731437 1992
50
The pathology of combined heart-lung transplantation: an autopsy study. 62
3142814 1988

Variations for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

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

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SOX18 NM_018419.3(SOX18):c.310G>C (p.Ala104Pro) SNV Pathogenic
8000 rs28936692 GRCh37: 20:62680560-62680560
GRCh38: 20:64049207-64049207
2 SOX18 NM_018419.3(SOX18):c.283T>A (p.Trp95Arg) SNV Pathogenic
8001 rs28936693 GRCh37: 20:62680587-62680587
GRCh38: 20:64049234-64049234
3 SOX18 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:

73
# 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
2 10.78 SOX7 SOX17
3 10.19 SOX17 FOXC2

GO Terms for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

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

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 regulation of DNA-templated transcription GO:0006355 10.2 SOX7 SOX18 SOX17 PROX1 NR2F2 FOXC2
2 angiogenesis GO:0001525 10.13 CALCRL FLT4 SOX17 SOX18
3 heart development GO:0007507 10.04 SOX18 SOX17 FOXC2 CALCRL
4 anatomical structure morphogenesis GO:0009653 10.01 SOX7 SOX18 SOX17 FOXC2
5 positive regulation of endothelial cell migration GO:0010595 9.95 PROX1 FOXC2 FLT4
6 ventricular cardiac muscle tissue morphogenesis GO:0055010 9.88 PROX1 FOXC2
7 blood vessel morphogenesis GO:0048514 9.87 NR2F2 FLT4
8 vasculature development GO:0001944 9.86 SOX18 FLT4
9 endoderm formation GO:0001706 9.84 SOX7 SOX17
10 regulation of stem cell proliferation GO:0072091 9.81 SOX18 SOX17
11 lymphatic endothelial cell differentiation GO:0060836 9.76 PROX1 SOX18
12 endocardial cell differentiation GO:0060956 9.73 SOX18 SOX17
13 embryonic heart tube development GO:0035050 9.73 FOXC2 SOX17 SOX18
14 stem cell fate specification GO:0048866 9.67 SOX18 SOX17
15 endocardium formation GO:0060214 9.63 SOX18 SOX17 PROX1
16 lymphatic endothelial cell fate commitment GO:0060838 9.62 PROX1 NR2F2
17 lymphangiogenesis GO:0001946 9.56 SOX18 PROX1 FOXC2 FLT4
18 lymph vessel development GO:0001945 9.1 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 DNA-binding transcription factor activity GO:0003700 9.81 SOX7 SOX18 SOX17 PROX1 NR2F2 FOXC2
2 transcription cis-regulatory region binding GO:0000976 9.65 SOX7 SOX18 SOX17 PROX1 FOXC2
3 sequence-specific DNA binding GO:0043565 9.23 SOX7 SOX18 SOX17 PROX1 NR2F2 FOXC2

Sources for Hypotrichosis-Lymphedema-Telangiectasia Syndrome

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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