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Ehlers-Danlos syndrome, classic type, 2(EDSCL2)

MedGen UID:
120628
Concept ID:
C0268336
Disease or Syndrome
Synonyms: EDSCL2; Ehlers-Danlos syndrome type 2 (formerly); Ehlers-Danlos syndrome, type 2
SNOMED CT: Ehlers-Danlos syndrome classic type 2 (1287094005)
 
Gene (location): COL5A2 (2q32.2)
 
Monarch Initiative: MONDO:0019568
OMIM®: 130010

Disease characteristics

Excerpted from the GeneReview: Classic Ehlers-Danlos Syndrome
Classic Ehlers-Danlos syndrome (cEDS) is a heritable connective tissue disorder characterized by skin hyperextensibility, atrophic scarring, and generalized joint hypermobility (GJH). The skin is soft, velvety, or doughy to the touch. In addition, the skin is hyperextensible, meaning that it extends easily and snaps back after release. The skin is fragile, as manifested by splitting of the dermis following relatively minor trauma, especially over pressure points (knees, elbows) and areas prone to trauma (shins, forehead, chin). Wound healing is poor, and stretching, thinning, and pigmentation of scars is characteristic, leading to the presence of atrophic and/or hemosiderotic scars. Easy bruising is also a hallmark of cEDS. GJH is present in most but not all affected individuals, evidenced by the presence of a Beighton score of five or greater, either on examination or historically. Joint instability complications may comprise sprains and dislocations/subluxations. Mild muscle hypotonia with delayed motor development, fatigue and muscle cramps, and some skeletal morphologic alterations (scoliosis, pectus deformities, genus/hallux valgus, pes planus) are regularly observed. While aortic root dilatation and mitral valve prolapse are seen in cEDS, they are rarely clinically significant. Arterial aneurysm and rupture have been reported in a few individuals with cEDS. [from GeneReviews]
Authors:
Fransiska Malfait  |  Sofie Symoens  |  Delfien Syx   view full author information

Additional description

From OMIM
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. The main features of classic Ehlers-Danlos syndrome are loose-jointedness and fragile, bruisable skin that heals with peculiar 'cigarette-paper' scars (Beighton, 1993). There are both severe and mild forms of classic EDS, previously designated EDS I and EDS II, respectively. For a general phenotypic description and a discussion of genetic heterogeneity of classic EDS, see 130000.  http://www.omim.org/entry/130010

Clinical features

From HPO
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Hernia
MedGen UID:
6816
Concept ID:
C0019270
Finding
The protrusion of part of an organ or fibroadipose tissue through an abnormal opening.
Congenital hip dislocation
MedGen UID:
9258
Concept ID:
C0019555
Disease or Syndrome
Recurrent joint dislocation
MedGen UID:
102356
Concept ID:
C0158100
Injury or Poisoning
Dislocation of a given joint repeated times.
Generalized joint hypermobility
MedGen UID:
322888
Concept ID:
C1836308
Finding
Joint hypermobility (ability of a joint to move beyond its normal range of motion) affecting many or all joints of the body. In individuals with Joint hypermobility at multiple sites (usually five or more), the term generalized joint hypermobility is preferred.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Hemoptysis
MedGen UID:
5502
Concept ID:
C0019079
Sign or Symptom
Coughing up (expectoration) of blood or blood-streaked sputum from the larynx, trachea, bronchi, or lungs.
Recurrent sinusitis
MedGen UID:
107919
Concept ID:
C0581354
Disease or Syndrome
A recurrent form of sinusitis.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Atrophic scars
MedGen UID:
57875
Concept ID:
C0162154
Pathologic Function
Scars that form a depression compared to the level of the surrounding skin because of damage to the collagen, fat or other tissues below the skin.
Hyperextensible skin
MedGen UID:
66023
Concept ID:
C0241074
Finding
A condition in which the skin can be stretched beyond normal, and then returns to its initial position.
Fragile skin
MedGen UID:
66826
Concept ID:
C0241181
Finding
Skin that splits easily with minimal injury.
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.
Soft skin
MedGen UID:
336730
Concept ID:
C1844592
Finding
Subjective impression of increased softness upon palpation of the skin.
Molluscoid pseudotumors
MedGen UID:
375465
Concept ID:
C1844597
Disease or Syndrome
Bluish-grey, spongy nodules associated with scars over pressure points and easily traumatized areas like the elbows and knees.
Soft, doughy skin
MedGen UID:
341366
Concept ID:
C1849043
Finding
A skin texture that is unusually soft (and may feel silky), and has a malleable consistency resembling that of dough.
Cigarette-paper scars
MedGen UID:
342099
Concept ID:
C1851828
Finding
Thin (atrophic) and wide scars.
Subcutaneous spheroids
MedGen UID:
927609
Concept ID:
C4293700
Pathologic Function
Small, hard cyst-like nodules, freely moveable in the subcutis over the bony prominences of the legs and arms, which have an outer calcified layer with a translucent core on x-ray.

Professional guidelines

PubMed

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

Curated

Mayer K, Kennerknecht I, Steinmann B
Eur J Hum Genet 2010 Sep;18(9) Epub 2010 Feb 10 doi: 10.1038/ejhg.2009.227. PMID: 20145674Free PMC Article

Recent clinical studies

Etiology

Basalom S, Rauch F
Curr Osteoporos Rep 2020 Apr;18(2):95-102. doi: 10.1007/s11914-020-00568-5. PMID: 32162201
Rolfes MC, Deyle DR, King KS, Hand JL, Graff AH, Derauf C
Child Abuse Negl 2019 May;91:95-101. Epub 2019 Mar 8 doi: 10.1016/j.chiabu.2019.03.008. PMID: 30856599Free PMC Article
Malfait F
Matrix Biol 2018 Oct;71-72:380-395. Epub 2018 Apr 27 doi: 10.1016/j.matbio.2018.04.013. PMID: 29709596
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
Mantle D, Wilkins RM, Preedy V
Med Hypotheses 2005;64(2):279-83. doi: 10.1016/j.mehy.2004.07.023. PMID: 15607555

Diagnosis

Venable E, Knight DRT, Thoreson EK, Baudhuin LM
Am J Med Genet C Semin Med Genet 2023 Jun;193(2):147-159. Epub 2023 Mar 9 doi: 10.1002/ajmg.c.32038. PMID: 36896471
Ghoraba HH, Moshfeghi DM
Eye (Lond) 2023 Jun;37(9):1936-1941. Epub 2022 Oct 14 doi: 10.1038/s41433-022-02278-x. PMID: 36241846Free PMC Article
Kempers MJ, Wessels M, Van Berendoncks A, van de Laar IM, de Leeuw N, Loeys B
Eur J Med Genet 2022 Oct;65(10):104593. Epub 2022 Aug 11 doi: 10.1016/j.ejmg.2022.104593. PMID: 35964930
Basalom S, Rauch F
Curr Osteoporos Rep 2020 Apr;18(2):95-102. doi: 10.1007/s11914-020-00568-5. PMID: 32162201
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

Therapy

Gaisl T, Giunta C, Bratton DJ, Sutherland K, Schlatzer C, Sievi N, Franzen D, Cistulli PA, Rohrbach M, Kohler M
Thorax 2017 Aug;72(8):729-735. Epub 2017 Jan 10 doi: 10.1136/thoraxjnl-2016-209560. PMID: 28073822
Chen W, Perritt AF, Morissette R, Dreiling JL, Bohn MF, Mallappa A, Xu Z, Quezado M, Merke DP
Hum Mutat 2016 Sep;37(9):893-7. Epub 2016 Jul 8 doi: 10.1002/humu.23028. PMID: 27297501Free PMC Article
Remvig L, Duhn P, Ullman S, Arokoski J, Jurvelin J, Safi A, Jensen F, Farholt S, Hove H, Juul-Kristensen B
Scand J Rheumatol 2010 Nov;39(6):511-7. Epub 2010 Aug 5 doi: 10.3109/03009741003781977. PMID: 20684735
Voermans NC, Knoop H, Bleijenberg G, van Engelen BG
J Pain Symptom Manage 2010 Sep;40(3):370-8. Epub 2010 Jun 25 doi: 10.1016/j.jpainsymman.2009.12.026. PMID: 20579833
Mantle D, Wilkins RM, Preedy V
Med Hypotheses 2005;64(2):279-83. doi: 10.1016/j.mehy.2004.07.023. PMID: 15607555

Prognosis

Rolfes MC, Deyle DR, King KS, Hand JL, Graff AH, Derauf C
Child Abuse Negl 2019 May;91:95-101. Epub 2019 Mar 8 doi: 10.1016/j.chiabu.2019.03.008. PMID: 30856599Free PMC Article
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
Gaisl T, Giunta C, Bratton DJ, Sutherland K, Schlatzer C, Sievi N, Franzen D, Cistulli PA, Rohrbach M, Kohler M
Thorax 2017 Aug;72(8):729-735. Epub 2017 Jan 10 doi: 10.1136/thoraxjnl-2016-209560. PMID: 28073822
Abayazeed A, Hayman E, Moghadamfalahi M, Cain D
J Radiol Case Rep 2014 Feb;8(2):63-9. Epub 2014 Feb 1 doi: 10.3941/jrcr.v8i2.1568. PMID: 24967021Free PMC Article
Mitchell AL, Schwarze U, Jennings JF, Byers PH
Hum Mutat 2009 Jun;30(6):995-1002. doi: 10.1002/humu.21000. PMID: 19370768Free PMC Article

Clinical prediction guides

Neshatian M, Mittal N, Huang S, Ali A, Khattignavong E, Bozec L
PLoS One 2024;19(8):e0307442. Epub 2024 Aug 22 doi: 10.1371/journal.pone.0307442. PMID: 39172992Free PMC Article
Venable E, Knight DRT, Thoreson EK, Baudhuin LM
Am J Med Genet C Semin Med Genet 2023 Jun;193(2):147-159. Epub 2023 Mar 9 doi: 10.1002/ajmg.c.32038. PMID: 36896471
Basalom S, Rauch F
Curr Osteoporos Rep 2020 Apr;18(2):95-102. doi: 10.1007/s11914-020-00568-5. PMID: 32162201
Malfait F
Matrix Biol 2018 Oct;71-72:380-395. Epub 2018 Apr 27 doi: 10.1016/j.matbio.2018.04.013. PMID: 29709596
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

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