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Ehlers-Danlos syndrome(EDS)

MedGen UID:
41720
Concept ID:
C0013720
Disease or Syndrome
Synonyms: ED syndrome; EDS
SNOMED CT: Ehlers-Danlos syndrome (398114001); Cutis hyperelastica dermatorrhexis (398114001); Dystrophia mesodermalis congenita (398114001); India rubber skin (398114001); Hereditary collagen dysplasia (398114001); Meekeren-Ehlers-Danlos syndrome (398114001); Cutis elastica (398114001); Cutis hyperelastica (398114001); Danlos disease (398114001); Fibrodysplasia elastica generalisata (398114001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Related genes: B3GALT6, SLC39A13, B4GALT7, ADAMTS2, COL5A2, COL5A1, COL3A1, COL1A1
 
Monarch Initiative: MONDO:0020066
OMIM® Phenotypic series: PS130000
Orphanet: ORPHA98249

Definition

Ehlers-Danlos syndrome is a group of disorders that affect connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. Defects in connective tissues cause the signs and symptoms of these conditions, which range from mildly loose joints to life-threatening complications.

The various forms of Ehlers-Danlos syndrome have been classified in several different ways. Originally, 11 forms of Ehlers-Danlos syndrome were named using Roman numerals to indicate the types (type I, type II, and so on). In 1997, researchers proposed a simpler classification (the Villefranche nomenclature) that reduced the number of types to six and gave them descriptive names based on their major features. In 2017, the classification was updated to include rare forms of Ehlers-Danlos syndrome that were identified more recently. The 2017 classification describes 13 types of Ehlers-Danlos syndrome.

An unusually large range of joint movement (hypermobility) occurs in most forms of Ehlers-Danlos syndrome, and it is a hallmark feature of the hypermobile type. Infants and children with hypermobility often have weak muscle tone (hypotonia), which can delay the development of motor skills such as sitting, standing, and walking. The loose joints are unstable and prone to dislocation and chronic pain. In the arthrochalasia type of Ehlers-Danlos syndrome, infants have hypermobility and dislocations of both hips at birth.

Many people with the Ehlers-Danlos syndromes have soft, velvety skin that is highly stretchy (elastic) and fragile. Affected individuals tend to bruise easily, and some types of the condition also cause abnormal scarring. People with the classical form of Ehlers-Danlos syndrome experience wounds that split open with little bleeding and leave scars that widen over time to create characteristic "cigarette paper" scars. The dermatosparaxis type of the disorder is characterized by loose skin that sags and wrinkles, and extra (redundant) folds of skin may be present.

Bleeding problems are common in the vascular type of Ehlers-Danlos syndrome and are caused by unpredictable tearing (rupture) of blood vessels and organs. These complications can lead to easy bruising, internal bleeding, a hole in the wall of the intestine (intestinal perforation), or stroke. During pregnancy, women with vascular Ehlers-Danlos syndrome may experience rupture of the uterus. Additional forms of Ehlers-Danlos syndrome that involve rupture of the blood vessels include the kyphoscoliotic, classical, and classical-like types.

Other types of Ehlers-Danlos syndrome have additional signs and symptoms. The cardiac-valvular type causes severe problems with the valves that control the movement of blood through the heart. People with the kyphoscoliotic type experience severe curvature of the spine that worsens over time and can interfere with breathing by restricting lung expansion. A type of Ehlers-Danlos syndrome called brittle cornea syndrome is characterized by thinness of the clear covering of the eye (the cornea) and other eye abnormalities. The spondylodysplastic type features short stature and skeletal abnormalities such as abnormally curved (bowed) limbs. Abnormalities of muscles, including hypotonia and permanently bent joints (contractures), are among the characteristic signs of the musculocontractural and myopathic forms of Ehlers-Danlos syndrome. The periodontal type causes abnormalities of the teeth and gums. [from MedlinePlus Genetics]

Term Hierarchy

Follow this link to review classifications for Ehlers-Danlos syndrome in Orphanet.

Professional guidelines

PubMed

Keser Z, Chiang CC, Benson JC, Pezzini A, Lanzino G
Vasc Health Risk Manag 2022;18:685-700. Epub 2022 Sep 2 doi: 10.2147/VHRM.S362844. PMID: 36082197Free PMC Article
Reychler G, De Backer MM, Piraux E, Poncin W, Caty G
Am J Med Genet A 2021 Oct;185(10):2986-2994. Epub 2021 Jun 19 doi: 10.1002/ajmg.a.62393. PMID: 34145717
Chopra P, Tinkle B, Hamonet C, Brock I, Gompel A, Bulbena A, Francomano C
Am J Med Genet C Semin Med Genet 2017 Mar;175(1):212-219. Epub 2017 Feb 10 doi: 10.1002/ajmg.c.31554. PMID: 28186390

Recent clinical studies

Etiology

Gensemer C, Burks R, Kautz S, Judge DP, Lavallee M, Norris RA
Dev Dyn 2021 Mar;250(3):318-344. Epub 2020 Aug 17 doi: 10.1002/dvdy.220. PMID: 32629534Free PMC Article
Kang J, Hanif M, Mirza E, Jaleel S
Eur J Obstet Gynecol Reprod Biol 2020 Dec;255:118-123. Epub 2020 Oct 17 doi: 10.1016/j.ejogrb.2020.10.033. PMID: 33113401
Malfait F, Castori M, Francomano CA, Giunta C, Kosho T, Byers PH
Nat Rev Dis Primers 2020 Jul 30;6(1):64. doi: 10.1038/s41572-020-0194-9. PMID: 32732924
Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, Bloom L, Bowen JM, Brady AF, Burrows NP, Castori M, Cohen H, Colombi M, Demirdas S, De Backer J, De Paepe A, Fournel-Gigleux S, Frank M, Ghali N, Giunta C, Grahame R, Hakim A, Jeunemaitre X, Johnson D, Juul-Kristensen B, Kapferer-Seebacher I, Kazkaz H, Kosho T, Lavallee ME, Levy H, Mendoza-Londono R, Pepin M, Pope FM, Reinstein E, Robert L, Rohrbach M, Sanders L, Sobey GJ, Van Damme T, Vandersteen A, van Mourik C, Voermans N, Wheeldon N, Zschocke J, Tinkle B
Am J Med Genet C Semin Med Genet 2017 Mar;175(1):8-26. doi: 10.1002/ajmg.c.31552. PMID: 28306229
Henderson FC Sr, Austin C, Benzel E, Bolognese P, Ellenbogen R, Francomano CA, Ireton C, Klinge P, Koby M, Long D, Patel S, Singman EL, Voermans NC
Am J Med Genet C Semin Med Genet 2017 Mar;175(1):195-211. Epub 2017 Feb 21 doi: 10.1002/ajmg.c.31549. PMID: 28220607

Diagnosis

Patel M, Khullar V
Am J Med Genet C Semin Med Genet 2021 Dec;187(4):579-585. Epub 2021 Nov 20 doi: 10.1002/ajmg.c.31959. PMID: 34799982
Kang J, Hanif M, Mirza E, Jaleel S
Eur J Obstet Gynecol Reprod Biol 2020 Dec;255:118-123. Epub 2020 Oct 17 doi: 10.1016/j.ejogrb.2020.10.033. PMID: 33113401
Riley B
J Am Osteopath Assoc 2020 Jan 1;120(1):30-32. doi: 10.7556/jaoa.2020.012. PMID: 31904772
Bowen JM, Sobey GJ, Burrows NP, Colombi M, Lavallee ME, Malfait F, Francomano CA
Am J Med Genet C Semin Med Genet 2017 Mar;175(1):27-39. Epub 2017 Feb 13 doi: 10.1002/ajmg.c.31548. PMID: 28192633
Tinkle B, Castori M, Berglund B, Cohen H, Grahame R, Kazkaz H, Levy H
Am J Med Genet C Semin Med Genet 2017 Mar;175(1):48-69. Epub 2017 Feb 1 doi: 10.1002/ajmg.c.31538. PMID: 28145611

Therapy

Reychler G, De Backer MM, Piraux E, Poncin W, Caty G
Am J Med Genet A 2021 Oct;185(10):2986-2994. Epub 2021 Jun 19 doi: 10.1002/ajmg.a.62393. PMID: 34145717
Song B, Yeh P, Nguyen D, Ikpeama U, Epstein M, Harrell J
Pain Physician 2020 Jul;23(4):429-438. PMID: 32709178
O'Shea KM, Aceves SS, Dellon ES, Gupta SK, Spergel JM, Furuta GT, Rothenberg ME
Gastroenterology 2018 Jan;154(2):333-345. Epub 2017 Jul 27 doi: 10.1053/j.gastro.2017.06.065. PMID: 28757265Free PMC Article
Engelbert RH, Juul-Kristensen B, Pacey V, de Wandele I, Smeenk S, Woinarosky N, Sabo S, Scheper MC, Russek L, Simmonds JV
Am J Med Genet C Semin Med Genet 2017 Mar;175(1):158-167. doi: 10.1002/ajmg.c.31545. PMID: 28306230
Mantle D, Wilkins RM, Preedy V
Med Hypotheses 2005;64(2):279-83. doi: 10.1016/j.mehy.2004.07.023. PMID: 15607555

Prognosis

Anderson LK, Lane KR
J Am Assoc Nurse Pract 2023 Oct 1;35(10):605-612. doi: 10.1097/JXX.0000000000000900. PMID: 37261967
Senser EM, Misra S, Henkin S
Cardiol Clin 2021 Nov;39(4):505-515. doi: 10.1016/j.ccl.2021.06.003. PMID: 34686263
Skeik N, Hyde JR, Olson SL, Thaler CM, Abuatiyeh W, Ahmed AK, Lyon DR, Witt DR, Garberich R, Sullivan T
Ann Vasc Surg 2019 Oct;60:128-146. Epub 2019 Jun 12 doi: 10.1016/j.avsg.2019.04.004. PMID: 31200053
Joseph AW, Joseph SS, Francomano CA, Kontis TC
JAMA Facial Plast Surg 2018 Jan 1;20(1):70-75. doi: 10.1001/jamafacial.2017.0793. PMID: 29121166
Frank M, Albuisson J, Ranque B, Golmard L, Mazzella JM, Bal-Theoleyre L, Fauret AL, Mirault T, Denarié N, Mousseaux E, Boutouyrie P, Fiessinger JN, Emmerich J, Messas E, Jeunemaitre X
Eur J Hum Genet 2015 Dec;23(12):1657-64. Epub 2015 Mar 11 doi: 10.1038/ejhg.2015.32. PMID: 25758994Free PMC Article

Clinical prediction guides

Tofts LJ, Simmonds J, Schwartz SB, Richheimer RM, O'Connor C, Elias E, Engelbert R, Cleary K, Tinkle BT, Kline AD, Hakim AJ, van Rossum MAJ, Pacey V
Orphanet J Rare Dis 2023 May 4;18(1):104. doi: 10.1186/s13023-023-02717-2. PMID: 37143135Free PMC Article
Senser EM, Misra S, Henkin S
Cardiol Clin 2021 Nov;39(4):505-515. doi: 10.1016/j.ccl.2021.06.003. PMID: 34686263
Reychler G, De Backer MM, Piraux E, Poncin W, Caty G
Am J Med Genet A 2021 Oct;185(10):2986-2994. Epub 2021 Jun 19 doi: 10.1002/ajmg.a.62393. PMID: 34145717
Song B, Yeh P, Nguyen D, Ikpeama U, Epstein M, Harrell J
Pain Physician 2020 Jul;23(4):429-438. PMID: 32709178
Malfait F, Wenstrup RJ, De Paepe A
Genet Med 2010 Oct;12(10):597-605. doi: 10.1097/GIM.0b013e3181eed412. PMID: 20847697

Recent systematic reviews

Shabani M, Abdollahi A, Brar BK, MacCarrick GL, Ambale Venkatesh B, Lima JAC, Bodurtha JN
Clin Genet 2023 Mar;103(3):261-267. Epub 2022 Oct 24 doi: 10.1111/cge.14245. PMID: 36210598
Thwaites PA, Gibson PR, Burgell RE
J Gastroenterol Hepatol 2022 Sep;37(9):1693-1709. Epub 2022 Jul 20 doi: 10.1111/jgh.15927. PMID: 35750466Free PMC Article
Martín-Martín M, Cortés-Martín J, Tovar-Gálvez MI, Sánchez-García JC, Díaz-Rodríguez L, Rodríguez-Blanque R
Int J Environ Res Public Health 2022 Feb 7;19(3) doi: 10.3390/ijerph19031870. PMID: 35162892Free PMC Article
Reychler G, De Backer MM, Piraux E, Poncin W, Caty G
Am J Med Genet A 2021 Oct;185(10):2986-2994. Epub 2021 Jun 19 doi: 10.1002/ajmg.a.62393. PMID: 34145717
El Masri H, Loong TH, Meurette G, Podevin J, Zinzindohoue F, Lehur PA
Tech Coloproctol 2018 May;22(5):333-341. Epub 2018 Apr 26 doi: 10.1007/s10151-018-1783-4. PMID: 29700641

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