EDSCLL
MCID: EHL081
MIFTS: 40

Ehlers-Danlos Syndrome, Classic-Like (EDSCLL)

Categories: Bone diseases, Endocrine diseases, Fetal diseases, Genetic diseases, Oral diseases, Rare diseases, Skin diseases

Aliases & Classifications for Ehlers-Danlos Syndrome, Classic-Like

MalaCards integrated aliases for Ehlers-Danlos Syndrome, Classic-Like:

Name: Ehlers-Danlos Syndrome, Classic-Like 57 72
Ehlers-Danlos Syndrome Due to Tenascin-X Deficiency 57 20 58 29 6
Tnx Deficiency 57 20 72 54
Ehlers-Danlos Syndrome, Classic-Like, 1 57 29 6
Eds Due to Tnx Deficiency 57 20 72
Ehlers-Danlos Syndrome, Autosomal Recessive, Due to Tenascin X Deficiency 72 13
Classical-Like Ehlers-Danlos Syndrome Type 1 20 58
Classical-Like Eds Type 1 20 58
Cleds Type 1 20 58
Edscll 57 72
Ehlers-Danlos Syndrome Caused by Tenascin-X Deficiency 70
Ehlers-Danlos Syndrome Due to Tenascin X Deficiency 72
Ehlers-Danlos Syndrome, Classic-Like Type 20
Ehlers-Danlos Syndrome Classic-Like 1 12
Classical-Like Ehlers-Danlos Syndrome 20
Eds, Classic-Like Type 20
Tenascin-X Deficiency 72
Classical-Like Eds 20
Cleds 20

Characteristics:

Orphanet epidemiological data:

58
classical-like ehlers-danlos syndrome type 1
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

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

Miscellaneous:
some patients may present with myopathic features
some patients have a contiguous gene defect involving both the cyp21a2 and the tnxb genes


HPO:

31
ehlers-danlos syndrome, classic-like:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare systemic and rhumatological diseases
Rare skin diseases
Developmental anomalies during embryogenesis
Rare odontological diseases


Summaries for Ehlers-Danlos Syndrome, Classic-Like

GARD : 20 Classical-like Ehlers-Danlos syndrome (EDS due to tenascin-X (TNX) deficiency) is a form of Ehlers Danlos Syndrome (EDS) characterized by an unusually large range of joint movement (hypermobility), skin that is soft, stretchy, and fragile and easy bruising. Other signs and symptoms might include: muscle weakness and wasting (atrophy), and protrusion of part of the stomach through the diaphragm in the chest cavity ( hiatal hernia ). Classical-like EDS is caused by mutations in both copies of the TNXB gene and is inherited in an autosomal recessive manner; however, some individuals with a mutation in only one copy of the TNXB gene can have symptoms similar to EDS hypermobility type including joint hypermobility and soft skin. These individuals do not typically have easy bruising and stretchy skin. Some individuals with classical-like EDS can have larger deletions of genetic material including other genes. These individuals may have additional symptoms. For example, sometimes deletions include both the TNXB gene and the CYP21A2 gene. Mutations within this gene are associated with one type of congenital adrenal hyperplasia (CAH), a group of genetic conditions that affect the glands that sit on top of the kidneys (adrenal glands). There is no cure for classical-like EDS. The treatment and management is focused on preventing serious complications and relieving associated signs and symptoms.

MalaCards based summary : Ehlers-Danlos Syndrome, Classic-Like, also known as ehlers-danlos syndrome due to tenascin-x deficiency, is related to ehlers-danlos syndrome and ehlers-danlos syndrome, classic-like, 2, and has symptoms including arthralgia An important gene associated with Ehlers-Danlos Syndrome, Classic-Like is TNXB (Tenascin XB). The drug Strawberry has been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, uterus and kidney, and related phenotypes are joint hyperflexibility and fatigue

Disease Ontology : 12 An Ehlers-Danlos syndrome that is characterized by hyperextensible skin, hypermobile joints, and tissue fragility and that has material basis in omozygous or heterozygous mutation in the tenascin-XB gene (TNXB) on chromosome 6p21.

OMIM® : 57 Classic-like Ehlers-Danlos syndrome is a connective tissue disorder characterized by hyperextensible skin, hypermobile joints, and tissue fragility (Burch et al., 1996). For a phenotypic description of classic-type EDS, see 130000. (606408) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Ehlers-Danlos syndrome, classic-like: A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSCLL patients lack atrophic scars, a major diagnostic criteria for classic Ehlers-Danlos syndrome. Delayed wound healing is only present in a subset of patients. EDSCLL inheritance is autosomal recessive.

Related Diseases for Ehlers-Danlos Syndrome, Classic-Like

Graphical network of the top 20 diseases related to Ehlers-Danlos Syndrome, Classic-Like:



Diseases related to Ehlers-Danlos Syndrome, Classic-Like

Symptoms & Phenotypes for Ehlers-Danlos Syndrome, Classic-Like

Human phenotypes related to Ehlers-Danlos Syndrome, Classic-Like:

58 31 (show all 33)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint hyperflexibility 58 31 hallmark (90%) Very frequent (99-80%) HP:0005692
2 fatigue 58 31 frequent (33%) Frequent (79-30%) HP:0012378
3 skeletal muscle atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003202
4 arthralgia 58 31 frequent (33%) Frequent (79-30%) HP:0002829
5 myalgia 58 31 frequent (33%) Frequent (79-30%) HP:0003326
6 sensory neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0000763
7 bruising susceptibility 58 31 frequent (33%) Frequent (79-30%) HP:0000978
8 hyperextensible skin 58 31 frequent (33%) Frequent (79-30%) HP:0000974
9 proximal muscle weakness 58 31 occasional (7.5%) Frequent (79-30%) HP:0003701
10 thin skin 58 31 frequent (33%) Frequent (79-30%) HP:0000963
11 hypotonia 31 frequent (33%) HP:0001252
12 mitral valve prolapse 58 31 occasional (7.5%) Occasional (29-5%) HP:0001634
13 arrhythmia 58 31 occasional (7.5%) Occasional (29-5%) HP:0011675
14 gastrointestinal hemorrhage 58 31 occasional (7.5%) Occasional (29-5%) HP:0002239
15 stroke 58 31 occasional (7.5%) Occasional (29-5%) HP:0001297
16 spina bifida occulta 58 31 occasional (7.5%) Occasional (29-5%) HP:0003298
17 adrenal hypoplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000835
18 precocious atherosclerosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0004416
19 proximal amyotrophy 31 occasional (7.5%) HP:0007126
20 muscle fiber splitting 31 occasional (7.5%) HP:0003555
21 increased connective tissue 31 occasional (7.5%) HP:0009025
22 joint hypermobility 58 31 Frequent (79-30%) HP:0001382
23 muscular hypotonia 58 Frequent (79-30%)
24 muscle weakness 58 Frequent (79-30%)
25 vesicoureteral reflux 31 HP:0000076
26 peripheral neuropathy 58 Frequent (79-30%)
27 hiatus hernia 31 HP:0002036
28 unilateral renal agenesis 31 HP:0000122
29 bicornuate uterus 31 HP:0000813
30 joint subluxation 31 HP:0032153
31 soft skin 31 HP:0000977
32 ambiguous genitalia, female 31 HP:0000061
33 quadricuspid aortic valve 31 HP:0031655

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal Limbs:
arthralgia
joint hypermobility
joint subluxation

Abdomen Gastrointestinal:
hiatus hernia

Genitourinary External Genitalia Female:
ambiguous genitalia (seen in patients with contiguous gene defect)

Genitourinary Kidneys:
single kidney (seen in patients with contiguous gene defect)

Muscle Soft Tissue:
proximal muscle weakness (in some patients)
proximal muscle atrophy (in some patients)
myopathic pattern seen on emg (in some patients)
internal nuclei seen on biopsy (in some patients)
muscle fiber splitting (in some patients)
more
Laboratory Abnormalities:
tenascin x deficiency (serum and fibroblasts)

Skin Nails Hair Skin:
hyperextensible skin
normal wound healing
easy bruisability
velvety skin
no scarring

Cardiovascular Heart:
quadricuspid aortic valve (seen in patients with contiguous gene defect)
mitral valve prolapse (seen in patients with contiguous gene defect)

Genitourinary Internal Genitalia Female:
bicornuate uterus (seen in patients with contiguous gene defect)

Genitourinary Bladder:
vesicoureteral reflux (seen in patients with contiguous gene defect)
urethral prolapse (seen in patients with contiguous gene defect)

Endocrine Features:
elevated serum 17-hydroxyprogesterone level (seen in patients with contiguous gene defect)

Clinical features from OMIM®:

606408 (Updated 05-Apr-2021)

UMLS symptoms related to Ehlers-Danlos Syndrome, Classic-Like:


arthralgia

Drugs & Therapeutics for Ehlers-Danlos Syndrome, Classic-Like

Drugs for Ehlers-Danlos Syndrome, Classic-Like (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Strawberry Approved

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Randomised Feasibility Trial of an Intermittent Low Energy Diet (ILED) and Continuous Low Energy Diet (CLED) in Patients With Type 1 Diabetes and Obesity Not yet recruiting NCT04674384

Search NIH Clinical Center for Ehlers-Danlos Syndrome, Classic-Like

Genetic Tests for Ehlers-Danlos Syndrome, Classic-Like

Genetic tests related to Ehlers-Danlos Syndrome, Classic-Like:

# Genetic test Affiliating Genes
1 Ehlers-Danlos Syndrome Due to Tenascin-X Deficiency 29 TNXB
2 Ehlers-Danlos Syndrome, Classic-Like, 1 29

Anatomical Context for Ehlers-Danlos Syndrome, Classic-Like

MalaCards organs/tissues related to Ehlers-Danlos Syndrome, Classic-Like:

40
Skeletal Muscle, Uterus, Kidney, Skin

Publications for Ehlers-Danlos Syndrome, Classic-Like

Articles related to Ehlers-Danlos Syndrome, Classic-Like:

(show all 16)
# Title Authors PMID Year
1
Tenascin-X deficiency is associated with Ehlers-Danlos syndrome. 57 6 54
9288108 1997
2
Compound heterozygous mutations of the TNXB gene cause primary myopathy. 6 57
23768946 2013
3
Elastic fiber abnormalities in hypermobility type Ehlers-Danlos syndrome patients with tenascin-X mutations. 6 57
15733269 2005
4
Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers-Danlos syndrome. 6 57
12865992 2003
5
A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency. 57 6
11642233 2001
6
The phenotypic spectrum of contiguous deletion of CYP21A2 and tenascin XB: quadricuspid aortic valve and other midline defects. 57 54
19921645 2009
7
Ehlers-Danlos syndrome due to tenascin-X deficiency: muscle weakness and contractures support overlap with collagen VI myopathies. 57 61
17702048 2007
8
Compound heterozygous mutations of the TNXB gene cause primary myopathy. 57
24300784 2014
9
Neuromuscular involvement in various types of Ehlers-Danlos syndrome. 57
19557868 2009
10
Tenascin-X deficiency in autosomal recessive Ehlers-Danlos syndrome. 57
15793839 2005
11
Ullrich congenital muscular dystrophy: connective tissue abnormalities in the skin support overlap with Ehlers-Danlos syndromes. 57
15690374 2005
12
Hypermobility in two Dutch school populations. 57
9228503 1997
13
Mechanism and consequences of the duplication of the human C4/P450c21/gene X locus. 6
1620134 1992
14
Hypermobility: features and differential incidence between the sexes. 57
3435571 1987
15
Recurrent gastrointestinal perforation in a patient with Ehlers-Danlos syndrome due to tenascin-X deficiency. 61
25772043 2015
16
Interactions of human tenascin-X domains with dermal extracellular matrix molecules. 54
17033827 2007

Variations for Ehlers-Danlos Syndrome, Classic-Like

ClinVar genetic disease variations for Ehlers-Danlos Syndrome, Classic-Like:

6 (show all 40)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TNXB TNXB, 30-KB DEL Deletion Pathogenic 8549 GRCh37:
GRCh38:
2 TNXB NM_001365276.2(TNXB):c.3290_3291del (p.Lys1097fs) Deletion Pathogenic 8550 rs764070148 GRCh37: 6:32052344-32052345
GRCh38: 6:32084567-32084568
3 TNXB NM_001365276.2(TNXB):c.2106_2107GT[7] (p.Val706_Glu707insTer) Microsatellite Pathogenic 8551 rs144556766 GRCh37: 6:32063512-32063513
GRCh38: 6:32095735-32095736
4 LOC106780803 , TNXB NM_001365276.2(TNXB):c.12220C>T (p.Arg4074Cys) SNV Pathogenic 144112 rs587777682 GRCh37: 6:32010130-32010130
GRCh38: 6:32042353-32042353
5 TNXB NM_001365276.2(TNXB):c.5362del (p.Thr1788fs) Deletion Pathogenic 996104 GRCh37: 6:32037555-32037555
GRCh38: 6:32069778-32069778
6 TNXB NM_001365276.2(TNXB):c.3322G>A (p.Val1108Met) SNV Pathogenic 8552 rs121912575 GRCh37: 6:32052313-32052313
GRCh38: 6:32084536-32084536
7 TNXB NM_001365276.2(TNXB):c.6521_6522del (p.Pro2174fs) Deletion Pathogenic 1032819 GRCh37: 6:32035460-32035461
GRCh38: 6:32067683-32067684
8 TNXB NM_001365276.2(TNXB):c.8613del (p.Phe2871fs) Deletion Pathogenic 1032821 GRCh37: 6:32021343-32021343
GRCh38: 6:32053566-32053566
9 LOC106780803 , TNXB NM_001365276.2(TNXB):c.12224G>A (p.Arg4075His) SNV Conflicting interpretations of pathogenicity 190375 rs201510617 GRCh37: 6:32010126-32010126
GRCh38: 6:32042349-32042349
10 LOC106780803 , TNXB NM_001365276.2(TNXB):c.12520G>A (p.Asp4174Asn) SNV Uncertain significance 190376 rs200523717 GRCh37: 6:32009661-32009661
GRCh38: 6:32041884-32041884
11 LOC106780803 , TNXB NM_001365276.2(TNXB):c.12530G>A (p.Ser4177Asn) SNV Uncertain significance 190377 rs199953230 GRCh37: 6:32009651-32009651
GRCh38: 6:32041874-32041874
12 TNXB NM_001365276.2(TNXB):c.4996C>T (p.Arg1666Ter) SNV Uncertain significance 208621 rs746016355 GRCh37: 6:32038186-32038186
GRCh38: 6:32070409-32070409
13 TNXB NM_001365276.2(TNXB):c.9661G>A (p.Val3221Met) SNV Uncertain significance 209196 rs367685759 GRCh37: 6:32017143-32017143
GRCh38: 6:32049366-32049366
14 TNXB NM_001365276.2(TNXB):c.9637A>G (p.Arg3213Gly) SNV Uncertain significance 209197 rs377386505 GRCh37: 6:32017167-32017167
GRCh38: 6:32049390-32049390
15 LOC106780803 , TNXB NM_001365276.2(TNXB):c.10633G>A (p.Glu3545Lys) SNV Uncertain significance 626034 rs1379154957 GRCh37: 6:32013077-32013077
GRCh38: 6:32045300-32045300
16 TNXB NM_001365276.2(TNXB):c.6177C>G (p.His2059Gln) SNV Uncertain significance 626035 rs551447544 GRCh37: 6:32036210-32036210
GRCh38: 6:32068433-32068433
17 TNXB NM_001365276.2(TNXB):c.5416T>C (p.Phe1806Leu) SNV Uncertain significance 626036 rs184813324 GRCh37: 6:32037501-32037501
GRCh38: 6:32069724-32069724
18 TNXB NM_001365276.2(TNXB):c.3212C>G (p.Thr1071Arg) SNV Uncertain significance 626037 rs573740606 GRCh37: 6:32052423-32052423
GRCh38: 6:32084646-32084646
19 TNXB NM_001365276.2(TNXB):c.861G>A (p.Arg287=) SNV Uncertain significance 626191 rs1406340228 GRCh37: 6:32064769-32064769
GRCh38: 6:32096992-32096992
20 TNXB NM_001365276.2(TNXB):c.2170C>T (p.Arg724Cys) SNV Uncertain significance 634508 rs138771398 GRCh37: 6:32063460-32063460
GRCh38: 6:32095683-32095683
21 TNXB NM_001365276.2(TNXB):c.7126G>T (p.Gly2376Cys) SNV Uncertain significance 634509 rs764295837 GRCh37: 6:32029976-32029976
GRCh38: 6:32062199-32062199
22 TNXB NM_001365276.2(TNXB):c.3002C>T (p.Pro1001Leu) SNV Uncertain significance 801017 rs768607753 GRCh37: 6:32053673-32053673
GRCh38: 6:32085896-32085896
23 LOC106780803 , TNXB NM_001365276.2(TNXB):c.10789C>T (p.Pro3597Ser) SNV Uncertain significance 689442 rs764559504 GRCh37: 6:32012921-32012921
GRCh38: 6:32045144-32045144
24 TNXB NM_001365276.2(TNXB):c.6544+8T>A SNV Uncertain significance 261149 rs150379644 GRCh37: 6:32035430-32035430
GRCh38: 6:32067653-32067653
25 TNXB NM_001365276.2(TNXB):c.7856C>T (p.Pro2619Leu) SNV Uncertain significance 521772 rs183760368 GRCh37: 6:32024650-32024650
GRCh38: 6:32056873-32056873
26 TNXB NM_001365276.2(TNXB):c.2030A>G (p.Asp677Gly) SNV Uncertain significance 426989 rs141190850 GRCh37: 6:32063600-32063600
GRCh38: 6:32095823-32095823
27 TNXB NM_001365276.2(TNXB):c.8761G>A (p.Val2921Met) SNV Uncertain significance 827991 rs529485424 GRCh37: 6:32021195-32021195
GRCh38: 6:32053418-32053418
28 TNXB NM_001365276.2(TNXB):c.2030A>G (p.Asp677Gly) SNV Uncertain significance 426989 rs141190850 GRCh37: 6:32063600-32063600
GRCh38: 6:32095823-32095823
29 TNXB NM_001365276.2(TNXB):c.4861G>A (p.Val1621Met) SNV Uncertain significance 1032816 GRCh37: 6:32039896-32039896
GRCh38: 6:32072119-32072119
30 TNXB NM_001365276.2(TNXB):c.5869C>T (p.His1957Tyr) SNV Uncertain significance 1032818 GRCh37: 6:32036632-32036632
GRCh38: 6:32068855-32068855
31 LOC106780803 , TNXB NM_001365276.2(TNXB):c.12180C>G (p.Cys4060Trp) SNV Uncertain significance 190374 rs56345590 GRCh37: 6:32010262-32010262
GRCh38: 6:32042485-32042485
32 LOC106780803 , TNXB NM_001365276.2(TNXB):c.11227G>A (p.Asp3743Asn) SNV Uncertain significance 989243 GRCh37: 6:32012194-32012194
GRCh38: 6:32044417-32044417
33 TNXB NM_001365276.2(TNXB):c.7546G>A (p.Ala2516Thr) SNV Uncertain significance 989281 GRCh37: 6:32026114-32026114
GRCh38: 6:32058337-32058337
34 TNXB NM_001365276.2(TNXB):c.6320C>G (p.Ser2107Cys) SNV Uncertain significance 989282 GRCh37: 6:32035662-32035662
GRCh38: 6:32067885-32067885
35 TNXB NM_001365276.2(TNXB):c.287T>A (p.Leu96His) SNV Uncertain significance 992504 GRCh37: 6:32065689-32065689
GRCh38: 6:32097912-32097912
36 TNXB NM_001365276.2(TNXB):c.562C>T (p.Pro188Ser) SNV Uncertain significance 992505 GRCh37: 6:32065068-32065068
GRCh38: 6:32097291-32097291
37 TNXB NM_001365276.2(TNXB):c.9072C>A (p.His3024Gln) SNV Uncertain significance 1032822 GRCh37: 6:32020490-32020490
GRCh38: 6:32052713-32052713
38 TNXB NM_001365276.2(TNXB):c.788G>A (p.Arg263His) SNV Uncertain significance 1032820 GRCh37: 6:32064842-32064842
GRCh38: 6:32097065-32097065
39 LOC106780803 , TNXB NM_001365276.2(TNXB):c.12170A>T (p.Asn4057Ile) SNV Benign 261120 rs17421133 GRCh37: 6:32010272-32010272
GRCh38: 6:32042495-32042495
40 TNXB NM_001365276.2(TNXB):c.7553G>A (p.Gly2518Glu) SNV Benign 261162 rs1009382 GRCh37: 6:32026107-32026107
GRCh38: 6:32058330-32058330

UniProtKB/Swiss-Prot genetic disease variations for Ehlers-Danlos Syndrome, Classic-Like:

72
# Symbol AA change Variation ID SNP ID
1 TNXB p.Arg29Trp VAR_046499 rs368512272
2 TNXB p.Val1108Met VAR_046500 rs121912575
3 TNXB p.Arg4074Cys VAR_072582 rs587777682

Expression for Ehlers-Danlos Syndrome, Classic-Like

Search GEO for disease gene expression data for Ehlers-Danlos Syndrome, Classic-Like.

Pathways for Ehlers-Danlos Syndrome, Classic-Like

GO Terms for Ehlers-Danlos Syndrome, Classic-Like

Cellular components related to Ehlers-Danlos Syndrome, Classic-Like according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 collagen-containing extracellular matrix GO:0062023 8.62 TNXB AEBP1

Molecular functions related to Ehlers-Danlos Syndrome, Classic-Like according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix structural constituent GO:0005201 8.96 TNXB AEBP1
2 collagen binding GO:0005518 8.62 TNXB AEBP1

Sources for Ehlers-Danlos Syndrome, Classic-Like

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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