MCID: EHL054
MIFTS: 47

Ehlers-Danlos Syndrome, Type Vi

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

Aliases & Classifications for Ehlers-Danlos Syndrome, Type Vi

MalaCards integrated aliases for Ehlers-Danlos Syndrome, Type Vi:

Name: Ehlers-Danlos Syndrome, Type Vi 54 13
Nevo Syndrome 50 24 71 69
Eds Via 50 24 71
Ehlers-Danlos Syndrome Oculoscoliotic Type 50 71
Eds Vi 71 52
Ehlers-Danlos Syndrome, Kyphoscoliosis Type 50
Ehlers-Danlos Syndrome, Kyphoscoliotic Type 50
Ehlers-Danlos Syndrome, Oculoscoliotic Type 50
Ehlers-Danlos Syndrome Kyphoscoliotic Type 71
Kyphoscoliotic Ehlers-Danlos Syndrome 50
Ehlers-Danlos Syndrome Type Via 24
Ehlers-Danlos Syndrome Type 6a 50
Ehlers-Danlos Syndrome Type 6 69
Eds, Kyphoscoliotic Type 50
Eds, Oculoscoliotic Type 50
Ehlers-Danlos Syndrome 6 71
Kyphoscoliotic Eds 50
Eds6a 71
Keds 50
Eds6 71

Characteristics:

OMIM:

54
Inheritance:
autosomal recessive


HPO:

32
ehlers-danlos syndrome, type vi:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Ehlers-Danlos Syndrome, Type Vi

OMIM : 54
The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders that share the common features of skin hyperextensibility, articular hypermobility, and tissue fragility (Beighton et al., 1998). Beighton et al. (1998) reported on a revised nosology of the Ehlers-Danlos syndromes, designated the Villefranche classification. Major and minor diagnostic criteria were defined for each type and complemented whenever possible with laboratory findings. Six main descriptive types were substituted for earlier types numbered with Roman numerals: classic type (EDS I and II), hypermobility type (EDS III), vascular type (EDS IV), kyphoscoliosis type (EDS VI), arthrochalasia type (EDS VIIA and VIIB), and dermatosparaxis type (EDS VIIC). Six other forms were listed, including a category of 'unspecified forms.' The major characteristics of EDS type VI are severe muscle hypotonia at birth, generalized joint laxity, scoliosis at birth, and scleral fragility and rupture of the ocular globe (Beighton et al., 1998). Nevo syndrome, previously thought to be a distinct entity, is identical to EDS type VI (Voermans et al., 2009). (225400)

MalaCards based summary : Ehlers-Danlos Syndrome, Type Vi, also known as nevo syndrome, is related to ehlers-danlos syndrome, kyphoscoliotic form and ehlers-danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss, and has symptoms including scoliosis, visual impairment and myopia. An important gene associated with Ehlers-Danlos Syndrome, Type Vi is PLOD1 (Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 1), and among its related pathways/superpathways are Collagen chain trimerization and Degradation of the extracellular matrix. The drugs Folic Acid and Riboflavin have been mentioned in the context of this disorder. Affiliated tissues include skin, bone and heart, and related phenotype is Increased shRNA abundance (Z-score > 2).

NIH Rare Diseases : 50 kyphoscoliotic ehlers-danlos syndrome is an inheritedconnective tissue disorder that is caused by defects in a protein called collagen. common signs and symptoms include hyperextensible skin that is fragile and bruises easily; joint hypermobility; severe hypotonia at birth; progressive kyphoscoliosis (kyphosis and scoliosis); and fragility of the sclera. kyphoscoliosis eds is caused by changes (mutations) in the plod1 gene or the fkbp14 gene  and it is inherited in an autosomal recessive manner. treatment is focused on preventing serious complications and relieving associated signs and symptoms. last updated: 4/20/2017

UniProtKB/Swiss-Prot : 71 Ehlers-Danlos syndrome 6: A connective tissue disorder characterized by generalized joint hypermobility, hyperextensible skin, atrophic cutaneous scars due to tissue fragility, progressive kyphoscoliosis already present at birth, ocular manifestations, arterial rupture, easy bruising, severe neonatal muscle hypotonia and delayed motor development.

Related Diseases for Ehlers-Danlos Syndrome, Type Vi

Graphical network of the top 20 diseases related to Ehlers-Danlos Syndrome, Type Vi:



Diseases related to Ehlers-Danlos Syndrome, Type Vi

Symptoms & Phenotypes for Ehlers-Danlos Syndrome, Type Vi

Symptoms via clinical synopsis from OMIM:

54

Muscle Soft Tissue:
hypotonia

Head And Neck- Eyes:
myopia
retinal detachment
epicanthal folds
glaucoma
microcornea
more
Skeletal:
joint laxity
osteoporosis
recurrent joint dislocations

Prenatal Manifestations- Delivery:
premature rupture of membranes

Genitourinary- External Genitalia Male:
inguinal hernia

Prenatal Manifestations- Movement:
decreased fetal movement

Genitourinary- Bladder:
bladder diverticula

Growth- Height:
normal to tall stature

Cardiovascular- Vascular:
arterial rupture

Cardiovascular- Heart:
cardiac failure (secondary to chest deformity)

Respiratory- Lung:
recurrent episodes of pneumonia

Neurologic- Central Nervous System:
delayed motor development

Head And Neck- Nose:
depressed nasal bridge

Skeletal- Spine:
kyphosis
congenital scoliosis, progressive

Skeletal- Feet:
talipes equinovarus
pes planus

Skeletal- Hands:
arachnodactyly

Skin Nails & Hair- Skin:
easy bruisability
molluscoid pseudotumors
hyperextensible skin
excessive wrinkled skin (palms and soles)
soft thin skin
more
Growth- Other:
marfanoid habitus

Abdomen- Gastroin testinal:
gastrointestinal hemorrhage

Head And Neck- Teeth:
tooth crowding

Respiratory:
decreased pulmonary function (secondary to chest deformity)
respiratory insufficiency (secondary to chest deformity)

Laboratory- Abnormalities:
lysyl hydroxylase deficiency
decreased dermal hydroxylysine content


Clinical features from OMIM:

225400

Human phenotypes related to Ehlers-Danlos Syndrome, Type Vi:

32 (show top 50) (show all 53)
id Description HPO Frequency HPO Source Accession
1 scoliosis 32 hallmark (90%) HP:0002650
2 visual impairment 32 frequent (33%) HP:0000505
3 myopia 32 hallmark (90%) HP:0000545
4 retinal detachment 32 frequent (33%) HP:0000541
5 depressed nasal bridge 32 HP:0005280
6 joint laxity 32 HP:0001388
7 kyphosis 32 hallmark (90%) HP:0002808
8 premature rupture of membranes 32 HP:0001788
9 glaucoma 32 frequent (33%) HP:0000501
10 osteoporosis 32 HP:0000939
11 neonatal hypotonia 32 hallmark (90%) HP:0001319
12 microcornea 32 frequent (33%) HP:0000482
13 aortic dissection 32 hallmark (90%) HP:0002647
14 talipes equinovarus 32 occasional (7.5%) HP:0001762
15 thin skin 32 HP:0000963
16 inguinal hernia 32 frequent (33%) HP:0000023
17 blindness 32 HP:0000618
18 keratoconus 32 frequent (33%) HP:0000563
19 motor delay 32 HP:0001270
20 congestive heart failure 32 HP:0001635
21 respiratory insufficiency 32 HP:0002093
22 pes planus 32 HP:0001763
23 mitral valve prolapse 32 hallmark (90%) HP:0001634
24 tall stature 32 HP:0000098
25 joint hyperflexibility 32 hallmark (90%) HP:0005692
26 arachnodactyly 32 HP:0001166
27 decreased fetal movement 32 HP:0001558
28 epicanthus 32 HP:0000286
29 muscular hypotonia 32 HP:0001252
30 recurrent pneumonia 32 HP:0006532
31 molluscoid pseudotumors 32 HP:0000993
32 blue sclerae 32 HP:0000592
33 retinopathy 32 frequent (33%) HP:0000488
34 gait disturbance 32 hallmark (90%) HP:0001288
35 dental crowding 32 HP:0000678
36 generalized joint laxity 32 hallmark (90%) HP:0002761
37 soft skin 32 HP:0000977
38 hyperextensible skin 32 frequent (33%) HP:0000974
39 joint dislocation 32 HP:0001373
40 gastrointestinal hemorrhage 32 HP:0002239
41 corneal dystrophy 32 occasional (7.5%) HP:0001131
42 arterial dissection 32 hallmark (90%) HP:0005294
43 abnormality of metabolism/homeostasis 32 hallmark (90%) HP:0001939
44 abnormality of the hip bone 32 frequent (33%) HP:0003272
45 atypical scarring of skin 32 hallmark (90%) HP:0000987
46 disproportionate tall stature 32 HP:0001519
47 bruising susceptibility 32 HP:0000978
48 bladder diverticulum 32 HP:0000015
49 subcutaneous hemorrhage 32 frequent (33%) HP:0001933
50 palmoplantar cutis laxa 32 HP:0007517

UMLS symptoms related to Ehlers-Danlos Syndrome, Type Vi:


joint laxity

GenomeRNAi Phenotypes related to Ehlers-Danlos Syndrome, Type Vi according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-107 9.55 PLOD2
2 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.55 PLOD2
3 Increased shRNA abundance (Z-score > 2) GR00366-A-129 9.55 PLOD2
4 Increased shRNA abundance (Z-score > 2) GR00366-A-137 9.55 PLOD2
5 Increased shRNA abundance (Z-score > 2) GR00366-A-157 9.55 PLOD2
6 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.55 PLOD2
7 Increased shRNA abundance (Z-score > 2) GR00366-A-189 9.55 PLOD2
8 Increased shRNA abundance (Z-score > 2) GR00366-A-19 9.55 PLOD2
9 Increased shRNA abundance (Z-score > 2) GR00366-A-197 9.55 PLOD1
10 Increased shRNA abundance (Z-score > 2) GR00366-A-201 9.55 PLOD1
11 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.55 PLOD1
12 Increased shRNA abundance (Z-score > 2) GR00366-A-32 9.55 PLOD1 PLOD2
13 Increased shRNA abundance (Z-score > 2) GR00366-A-42 9.55 PLOD2
14 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.55 PLOD1
15 Increased shRNA abundance (Z-score > 2) GR00366-A-82 9.55 PLOD2
16 Increased shRNA abundance (Z-score > 2) GR00366-A-88 9.55 PLOD1

Drugs & Therapeutics for Ehlers-Danlos Syndrome, Type Vi

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

(show all 11)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Folic Acid Approved, Nutraceutical, Vet_approved 59-30-3 6037
2
Riboflavin Approved, Nutraceutical, Vet_approved 83-88-5 493570
3 Dermatologic Agents
4 Micronutrients
5 Photosensitizing Agents
6 Trace Elements
7 Vitamin B Complex
8 Vitamins
9 Folate Nutraceutical
10 Vitamin B2 Nutraceutical
11 Vitamin B9 Nutraceutical

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Riboflavin Corneal Crosslinking for Brittle Cornea Syndrome and Ehlers-Danlos Syndrome Type VI Unknown status NCT01307527 Riboflavin
2 The Impact of Exercise Training on Living Quality in Multiple Sclerosis Individuals Completed NCT03222596

Search NIH Clinical Center for Ehlers-Danlos Syndrome, Type Vi

Genetic Tests for Ehlers-Danlos Syndrome, Type Vi

Genetic tests related to Ehlers-Danlos Syndrome, Type Vi:

id Genetic test Affiliating Genes
1 Ehlers-Danlos Syndrome Type Via 24 PLOD1
2 Nevo Syndrome 24

Anatomical Context for Ehlers-Danlos Syndrome, Type Vi

MalaCards organs/tissues related to Ehlers-Danlos Syndrome, Type Vi:

39
Skin, Bone, Heart, Eye

Publications for Ehlers-Danlos Syndrome, Type Vi

Articles related to Ehlers-Danlos Syndrome, Type Vi:

(show all 24)
id Title Authors Year
1
Blunt aortic trauma in a patient with the Ehlers-Danlos syndrome type VI. ( 26956239 )
2016
2
Ehlers-Danlos Syndrome Type VI in a 17-Year-Old Iranian Boy with Severe Muscular Weakness - A Diagnostic Challenge? ( 23056730 )
2010
3
Abnormal retinal blood vessels in Ehlers-Danlos syndrome type VI. ( 18158597 )
2007
4
Orthodontic treatment protocol of Ehlers-Danlos syndrome type VI. ( 16448289 )
2006
5
A case of Ehlers Danlos syndrome type VI. ( 17100196 )
2006
6
Successful mitral valve replacement in a patient with Ehlers-Danlos syndrome type VI. ( 15975394 )
2005
7
Corneal perforation with minor trauma: Ehlers-Danlos syndrome type VI. ( 16156158 )
2005
8
Ehlers-Danlos syndrome type VI with cystic malformations of the meninges in a 7-year-old girl. ( 14872341 )
2004
9
Mutational analysis of the lysyl hydroxylase 1 gene (PLOD) in six unrelated patients with Ehlers-Danlos syndrome type VI: prenatal exclusion of this disorder in one family. ( 10874315 )
2000
10
Deletion of cysteine 369 in lysyl hydroxylase 1 eliminates enzyme activity and causes Ehlers-Danlos syndrome type VI. ( 10686424 )
2000
11
A nonsense codon of exon 14 reduces lysyl hydroxylase mRNA and leads to aberrant RNA splicing in a patient with Ehlers-Danlos syndrome type VI. ( 10729709 )
2000
12
Mutations in the lysyl hydroxylase 1 gene that result in enzyme deficiency and the clinical phenotype of Ehlers-Danlos syndrome type VI. ( 11001813 )
2000
13
Prenatal exclusion of Ehlers-Danlos syndrome type VI by mutational analysis. ( 9893157 )
1999
14
A patient with Ehlers-Danlos syndrome type VI is homozygous for a premature termination codon in exon 14 of the lysyl hydroxylase 1 gene. ( 10329027 )
1999
15
Ehlers-Danlos syndrome type VI: lysyl hydroxylase deficiency due to a novel point mutation (W612C). ( 9617436 )
1998
16
A splice-site mutation that induces exon skipping and reduction in lysyl hydroxylase mRNA levels but does not create a nonsense codon in Ehlers-Danlos syndrome type VI. ( 9502428 )
1998
17
A common duplication in the lysyl hydroxylase gene of patients with Ehlers Danlos syndrome type VI results in preferential stimulation of lysyl hydroxylase activity and mRNA by hydralazine. ( 9344473 )
1997
18
Ehlers-Danlos syndrome type VI results from a nonsense mutation and a splice site-mediated exon-skipping mutation in the lysyl hydroxylase gene. ( 9220536 )
1997
19
The mRNA and the activity of lysyl hydroxylase are up-regulated by the administration of ascorbate and hydralazine to human skin fibroblasts from a patient with Ehlers-Danlos syndrome type VI. ( 7646078 )
1995
20
Structure and expression of the human lysyl hydroxylase gene (PLOD): introns 9 and 16 contain Alu sequences at the sites of recombination in Ehlers-Danlos syndrome type VI patients. ( 7713497 )
1994
21
A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote for mutations in the lysyl hydroxylase gene. ( 8163671 )
1994
22
A homozygous stop codon in the lysyl hydroxylase gene in two siblings with Ehlers-Danlos syndrome type VI. ( 1345174 )
1992
23
Brittle cornea syndrome: an heritable connective tissue disorder distinct from Ehlers-Danlos syndrome type VI and fragilitas oculi, with spontaneous perforations of the eye, blue sclerae, red hair, and normal collagen lysyl hydroxylation. ( 2112090 )
1990
24
Ascorbate regulation of collagen biosynthesis in Ehlers-Danlos syndrome, type VI. ( 3110540 )
1987

Variations for Ehlers-Danlos Syndrome, Type Vi

UniProtKB/Swiss-Prot genetic disease variations for Ehlers-Danlos Syndrome, Type Vi:

71
id Symbol AA change Variation ID SNP ID
1 PLOD1 p.Trp612Cys VAR_006355 rs121913553
2 PLOD1 p.Gly678Arg VAR_006356 rs121913551
3 PLOD1 p.Trp446Gly VAR_023466
4 PLOD1 p.Ala667Thr VAR_023467 rs199730384
5 PLOD1 p.His706Arg VAR_023468

ClinVar genetic disease variations for Ehlers-Danlos Syndrome, Type Vi:

6 (show all 13)
id Gene Variation Type Significance SNP ID Assembly Location
1 PLOD1 NM_000302.3(PLOD1): c.955C> T (p.Arg319Ter) single nucleotide variant Pathogenic rs121913550 GRCh37 Chromosome 1, 12018684: 12018684
2 PLOD1 NG_008159.1: g.(30134_30285)_(38781_39030)dup duplication Pathogenic GRCh38 Chromosome 1, 11959822: 11968718
3 PLOD1 NM_000302.3(PLOD1): c.2032G> A (p.Gly678Arg) single nucleotide variant Pathogenic rs121913551 GRCh37 Chromosome 1, 12034713: 12034713
4 PLOD1 NM_000302.3(PLOD1): c.1594_1596delGAG (p.Glu532del) deletion Pathogenic rs797044446 GRCh37 Chromosome 1, 12026317: 12026319
5 PLOD1 NM_000302.3(PLOD1): c.1651-2delA deletion Pathogenic rs797044447 GRCh37 Chromosome 1, 12027042: 12027042
6 PLOD1 NM_000302.3(PLOD1): c.1756_1902del deletion Pathogenic GRCh38 Chromosome 1, 11968235: 11971660
7 PLOD1 NM_000302.3(PLOD1): c.1533C> G (p.Tyr511Ter) single nucleotide variant Pathogenic rs121913552 GRCh37 Chromosome 1, 12025599: 12025599
8 PLOD1 NM_000302.3(PLOD1): c.579+1G> A single nucleotide variant Pathogenic rs797044448 GRCh37 Chromosome 1, 12012793: 12012793
9 PLOD1 NM_000302.3(PLOD1): c.1836G> C (p.Trp612Cys) single nucleotide variant Pathogenic rs121913553 GRCh37 Chromosome 1, 12030807: 12030807
10 PLOD1 NM_000302.3(PLOD1): c.2008C> T (p.Arg670Ter) single nucleotide variant Pathogenic rs121913554 GRCh37 Chromosome 1, 12033034: 12033034
11 PLOD1 NM_000302.3(PLOD1): c.327delG (p.Arg111Glyfs) deletion Pathogenic rs886042976 GRCh37 Chromosome 1, 12010438: 12010438
12 PLOD1 NM_000302.3(PLOD1): c.402delA (p.Asp135Thrfs) deletion Pathogenic rs886043926 GRCh37 Chromosome 1, 12010513: 12010513
13 PLOD1 NM_000302.3(PLOD1): c.1470+2T> C single nucleotide variant Pathogenic rs886043927 GRCh37 Chromosome 1, 12024844: 12024844

Expression for Ehlers-Danlos Syndrome, Type Vi

Search GEO for disease gene expression data for Ehlers-Danlos Syndrome, Type Vi.

Pathways for Ehlers-Danlos Syndrome, Type Vi

GO Terms for Ehlers-Danlos Syndrome, Type Vi

Cellular components related to Ehlers-Danlos Syndrome, Type Vi according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.13 COL1A1 PLOD1 PLOD2
2 rough endoplasmic reticulum membrane GO:0030867 8.62 PLOD1 PLOD2

Biological processes related to Ehlers-Danlos Syndrome, Type Vi according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 response to hypoxia GO:0001666 9.32 PLOD1 PLOD2
2 cellular protein modification process GO:0006464 9.26 PLOD1 PLOD2
3 protein O-linked glycosylation GO:0006493 9.16 PLOD1 PLOD2
4 peptidyl-lysine hydroxylation GO:0017185 8.96 PLOD1 PLOD2
5 hydroxylysine biosynthetic process GO:0046947 8.62 PLOD1 PLOD2

Molecular functions related to Ehlers-Danlos Syndrome, Type Vi according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 iron ion binding GO:0005506 9.37 PLOD1 PLOD2
2 dioxygenase activity GO:0051213 9.32 PLOD1 PLOD2
3 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen GO:0016705 9.26 PLOD1 PLOD2
4 L-ascorbic acid binding GO:0031418 9.16 PLOD1 PLOD2
5 procollagen glucosyltransferase activity GO:0033823 8.96 PLOD1 PLOD2
6 procollagen-lysine 5-dioxygenase activity GO:0008475 8.62 PLOD1 PLOD2

Sources for Ehlers-Danlos Syndrome, Type Vi

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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