Details of Disease

General Information of Disease (ID: DISSVBRR)

• Disease Name: Ehlers-Danlos syndrome
• Synonyms: ED syndrome; Danlos disease; skin elastic; Ehlers Danlos Syndrome; Ehlers Danlos syndrome; Ehler Danlos Syndrome; Ehlers Danlos Disease; Hereditary collagen dysplasia; EDS; Disease, Ehlers-Danlos; Ehlers-Danlos Disease; Fibrodysplasia elastica generalisata; elastic skin; Meekeren-Ehlers-Danlos syndrome; Disease, Ehlers Danlos; danlos ehlers syndrome; Danlos Disease, Ehlers; Dystrophia mesodermalis congenita; Syndrome, Ehlers-Danlos; Ehlers-Danlos syndromes
• Disease Class: LD28: Connective tissue syndrome
• Definition: The EhlersDanlos syndromes (EDS) are a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISYKSRF: Genetic disease
  DIS7GG31: Developmental defect during embryogenesis
  DISSVBRR: Ehlers-Danlos syndrome
• ICD Code:
  ICD-11: ICD-11: LD28.1
  Expand ICD-11: 'LD28.1
  Expand ICD-10: 'M35; 'M35.7; 'Q79.6
• Disease Identifiers:
  MONDO ID: MONDO_0020066
  MESH ID: D004535
  UMLS CUI: C0013720
  MedGen ID: 41720
  Orphanet ID: 98249
  SNOMED CT ID: 398114001

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
ACER-002	DMVW5LN	Phase 3	NA	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 11 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
PLOD1	TTEKJP3	moderate	Genetic Variation	[2]
ADAMTS4	TTYG6BU	Strong	Altered Expression	[3]
CIT	TT3BKTU	Strong	Biomarker	[4]
COL1A2	TTUABC1	Strong	Genetic Variation	[5]
CYP21A2	TTP4GLG	Strong	Genetic Variation	[6]
DMPK	TTZQTY2	Strong	Biomarker	[7]
IL1R2	TT51DEV	Strong	Biomarker	[8]
NPPC	TTRK0B9	Strong	Biomarker	[8]
NPR2	TTNB7IF	Strong	Altered Expression	[8]
PLOD2	TT8MEUD	Strong	Altered Expression	[9]
HCRT	TTU5HJP	Definitive	Altered Expression	[10]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC39A13	DTOTKBS	moderate	Biomarker	[11]

This Disease Is Related to 26 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ADAMTSL2	OTAXNV2U	Limited	Autosomal dominant	[12]
ATP6V0D2	OTMOZJO0	Limited	Autosomal recessive	[12]
ADAMTS2	OTTK22NO	Strong	Genetic Variation	[13]
AEBP1	OTBI1RZ6	Strong	Biomarker	[14]
ATP6V0A2	OTJBDX0Y	Strong	Biomarker	[15]
B3GALT4	OTLKSMQE	Strong	Genetic Variation	[16]
B3GALT6	OTF4HBAT	Strong	Biomarker	[17]
C1R	OTA0ZNIU	Strong	Genetic Variation	[18]
CENPJ	OTZCQZN5	Strong	Genetic Variation	[19]
CHST14	OT3FLH7U	Strong	Biomarker	[20]
COL12A1	OTHLTV53	Strong	Genetic Variation	[21]
COL1A1	OTI31178	Strong	Genetic Variation	[22]
COL3A1	OTT1EMLM	Strong	Genetic Variation	[22]
COL5A1	OT24078H	Strong	Genetic Variation	[23]
COL5A2	OT5VOSQE	Strong	Genetic Variation	[24]
COL5A3	OTCGC4DM	Strong	Biomarker	[25]
DSE	OTQ108VJ	Strong	Genetic Variation	[26]
EDA	OTAKS5WS	Strong	Biomarker	[27]
FAM20B	OTOA0UYT	Strong	Genetic Variation	[16]
FKBP14	OT55W5WC	Strong	Genetic Variation	[28]
MED18	OT6M6CQ8	Strong	Genetic Variation	[29]
PDSS2	OTEOQBMX	Strong	Biomarker	[30]
REM1	OTUXL0HC	Strong	Genetic Variation	[31]
SEMA6A	OTDQ7QAW	Strong	Genetic Variation	[32]
SP140	OTQZHFMT	Strong	Biomarker	[8]
TAB2	OTPZK76F	Strong	Genetic Variation	[33]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Arterial fragility in kyphoscoliotic Ehlers-Danlos syndrome.BMJ Case Rep. 2018 Jul 6;2018:bcr2018224423. doi: 10.1136/bcr-2018-224423.
• [3] Expanding the clinical and mutational spectrum of the Ehlers-Danlos syndrome, dermatosparaxis type.Genet Med. 2016 Sep;18(9):882-91. doi: 10.1038/gim.2015.188. Epub 2016 Jan 14.
• [4] Excessive daytime sleepiness may be associated with caudate denervation in Parkinson disease.J Neurol Sci. 2018 Apr 15;387:220-227. doi: 10.1016/j.jns.2018.02.032. Epub 2018 Feb 21.
• [5] COL1-related overlap disorder: A novel connective tissue disorder incorporating the osteogenesis imperfecta/Ehlers-Danlos syndrome overlap.Clin Genet. 2020 Mar;97(3):396-406. doi: 10.1111/cge.13683. Epub 2019 Dec 12.
• [6] Tenascin-X, Congenital Adrenal Hyperplasia, and the CAH-X Syndrome.Horm Res Paediatr. 2018;89(5):352-361. doi: 10.1159/000481911. Epub 2018 May 7.
• [7] Daytime sleepiness and myotonic dystrophy.Curr Neurol Neurosci Rep. 2013 Apr;13(4):340. doi: 10.1007/s11910-013-0340-9.
• [8] Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype.Sleep. 2016 Apr 1;39(4):743-55. doi: 10.5665/sleep.5620.
• [9] Decreased expression of lysyl hydroxylase 2 (LH2) in skin fibroblasts from three Ehlers-Danlos patients does not result from mutations in either the coding or proximal promoter region of the LH2 gene.Mol Genet Metab. 2004 Dec;83(4):312-21. doi: 10.1016/j.ymgme.2004.07.013.
• [10] Orexin/hypocretin levels in the cerebrospinal fluid and characteristics of patients with myotonic dystrophy type 1 with excessive daytime sleepiness.Neuropsychiatr Dis Treat. 2018 Feb 8;14:451-457. doi: 10.2147/NDT.S158651. eCollection 2018.
• [11] Morphometric analysis of thoracic aorta in Slc39a13/Zip13-KO mice.Cell Tissue Res. 2019 Apr;376(1):137-141. doi: 10.1007/s00441-018-2977-9. Epub 2019 Jan 4.
• [12] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [13] A homozygous ADAMTS2 nonsense mutation in a Doberman Pinscher dog with Ehlers Danlos syndrome and extreme skin fragility.Anim Genet. 2019 Oct;50(5):543-545. doi: 10.1111/age.12825. Epub 2019 Jul 11.
• [14] Bi-allelic AEBP1 mutations in two patients with Ehlers-Danlos syndrome.Hum Mol Genet. 2019 Jun 1;28(11):1853-1864. doi: 10.1093/hmg/ddz024.
• [15] Autosomal recessive cutis laxa type 2A (ARCL2A) mimicking Ehlers-Danlos syndrome by its dermatological manifestations: report of three affected patients.Am J Med Genet A. 2014 May;164A(5):1245-53. doi: 10.1002/ajmg.a.36411. Epub 2014 Jan 29.
• [16] Xylose phosphorylation functions as a molecular switch to regulate proteoglycan biosynthesis.Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):15723-8. doi: 10.1073/pnas.1417993111. Epub 2014 Oct 20.
• [17] A B3GALT6 variant in patient originally described as Al-Gazali syndrome and implicating the endoplasmic reticulum quality control in the mechanism of some 3GalT6-pathy mutations.Clin Genet. 2018 Jun;93(6):1148-1158. doi: 10.1111/cge.13236. Epub 2018 Mar 15.
• [18] A Chinese family with periodontal Ehlers-Danlos syndrome associated with missense mutation in the C1R gene.J Clin Periodontol. 2018 Nov;45(11):1311-1318. doi: 10.1111/jcpe.12988.
• [19] Women with symptoms of sleep-disordered breathing are less likely to be diagnosed and treated for sleep apnea than men.Sleep Med. 2017 Jul;35:17-22. doi: 10.1016/j.sleep.2017.02.032. Epub 2017 Apr 23.
• [20] Vascular abnormalities in the placenta of Chst14-/- fetuses: implications in the pathophysiology of perinatal lethality of the murine model and vascular lesions in human CHST14/D4ST1 deficiency.Glycobiology. 2018 Feb 1;28(2):80-89. doi: 10.1093/glycob/cwx099.
• [21] Novel defects in collagen XII and VI expand the mixed myopathy/Ehlers-Danlos syndrome spectrum and lead to variant-specific alterations in the extracellular matrix.Genet Med. 2020 Jan;22(1):112-123. doi: 10.1038/s41436-019-0599-6. Epub 2019 Jul 5.
• [22] Classical Ehlers-Danlos syndrome with a propensity to arterial events: A new report on a French family with a COL1A1 p.(Arg312Cys) variant.Clin Genet. 2020 Feb;97(2):357-361. doi: 10.1111/cge.13643. Epub 2019 Oct 1.
• [23] Compound phenotype of osteogenesis imperfecta and Ehlers-Danlos syndrome caused by combined mutations in COL1A1 and COL5A1.Biosci Rep. 2019 Jul 25;39(7):BSR20181409. doi: 10.1042/BSR20181409. Print 2019 Jul 31.
• [24] A case of Ehlers-Danlos syndrome presenting with widened atrophic scars of forehead, elbow, knee, and pretibial area: A case report.Medicine (Baltimore). 2019 Sep;98(37):e17138. doi: 10.1097/MD.0000000000017138.
• [25] The pro-alpha3(V) collagen chain. Complete primary structure, expression domains in adult and developing tissues, and comparison to the structures and expression domains of the other types V and XI procollagen chains.J Biol Chem. 2000 Mar 24;275(12):8749-59. doi: 10.1074/jbc.275.12.8749.
• [26] DSE associated musculocontractural EDS, a milder phenotype or phenotypic variability.Eur J Med Genet. 2020 Apr;63(4):103798. doi: 10.1016/j.ejmg.2019.103798. Epub 2019 Oct 23.
• [27] Altered fibronectin mRNA splicing in skin fibroblasts from Ehlers-Danlos syndrome patients: in situ hybridization analysis.Cell Biol Int Rep. 1991 Dec;15(12):1195-206. doi: 10.1016/0309-1651(91)90091-v.
• [28] Primary muscle involvement in a 15-year-old girl with the recurrent homozygous c.362dupC variant in FKBP14.Am J Med Genet A. 2019 Feb;179(2):317-321. doi: 10.1002/ajmg.a.61006. Epub 2018 Dec 18.
• [29] Targeted next-generation sequencing makes new molecular diagnoses and expands genotype-phenotype relationship in Ehlers-Danlos syndrome.Genet Med. 2016 Nov;18(11):1119-1127. doi: 10.1038/gim.2016.14. Epub 2016 Mar 24.
• [30] Association between Sleep Disturbances and Daytime Somnolence in Parkinson's Disease.Eur Neurol. 2018;80(5-6):268-276. doi: 10.1159/000496937. Epub 2019 Feb 7.
• [31] Excessive daytime sleepiness and fatigue in neurological disorders.Sleep Breath. 2020 Jun;24(2):413-424. doi: 10.1007/s11325-019-01921-4. Epub 2019 Aug 23.
• [32] Kyphoscoliotic type of Ehlers-Danlos Syndrome (EDS VIA) in six Egyptian patients presenting with a homogeneous clinical phenotype.Eur J Pediatr. 2015 Jan;174(1):105-12. doi: 10.1007/s00431-014-2429-9. Epub 2014 Oct 3.
• [33] A recognizable systemic connective tissue disorder with polyvalvular heart dystrophy and dysmorphism associated with TAB2 mutations. Clin Genet. 2018 Jan;93(1):126-133. doi: 10.1111/cge.13032. Epub 2017 Aug 21.