Genetics of Ehlers-Danlos Syndrome Medication

  • Author: Robert D Steiner, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Aug 17, 2011
 
 

Medication Summary

High-dose ascorbic acid has been used, although it is not considered the standard of care (see Treatment).

Desmopressin may normalize bleeding time in Ehlers-Danlos syndrome (EDS), but further studies are needed to establish safety and efficacy of this medication in treatment and/or prevention of bleeding in patients.[18]

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Contributor Information and Disclosures
Author

Robert D Steiner, MD  Credit Unions for Kids Professor of Pediatric Research; Faculty, Pediatrics, Molecular and Medical Genetics, and Program in Molecular and Cellular Biosciences; Vice Chair for Research in Pediatrics, Doernbecher Children's Hospital, Oregon Health and Science University; Director and Consulting Staff, Metabolic Bone Disease Clinic, Shriner's Hospital

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research

Disclosure: Amicus Honoraria Consulting; Actelion Honoraria Consulting; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Consulting; Genzyme Honoraria Consulting; Shire Honoraria Consulting

Specialty Editor Board

Michael Fasullo, PhD  Senior Scientist, Ordway Research Institute; Associate Professor, State University of New York at Albany; Adjunct Associate Professor, Center for Immunology and Microbial Disease, Albany Medical College

Michael Fasullo, PhD is a member of the following medical societies: American Society for Biochemistry and Molecular Biology, Environmental Mutagen Society, Genetics Society of America, and Radiation Research Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David Flannery, MD, FAAP, FACMG  Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics and American College of Medical Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthors G Bradley Schaefer, MD, and Melanie G Pepin, MS, CGC, to the original writing and development of this article.

References

  1. Beighton P. The Ehlers-Danlos syndromes. In: McKusick VA, Beighton P, eds. McKusick's Heritable Disorders of Connective Tissue. 5th ed. Mosby-Year Book; 1993:189-93.

  2. Tschernogobow A. Ein fall von cutis laxa. Jahresber Ges Med. 1892;27:562.

  3. Gawthrop F, Mould R, Sperritt A, et al. Ehlers-Danlos syndrome. BMJ. Sep 1 2007;335(7617):448-50. [Medline].

  4. Childs SG. Musculoskeletal manifestations of Ehlers-Danlos syndrome. Orthop Nurs. Mar-Apr 2010;29(2):133-9; quiz 140-1. [Medline].

  5. Rombaut L, Malfait F, Cools A, de Paepe A, Calders P. Musculoskeletal complaints, physical activity and health-related quality of life among patients with the Ehlers-Danlos syndrome hypermobility type. Disabil Rehabil. Feb 15 2010;[Medline].

  6. Chen CW, Jao SW. Images in clinical medicine. Ehlers-Danlos syndrome. N Engl J Med. Sep 13 2007;357(11):e12. [Medline].

  7. Beighton P, De Paepe A, Steinmann B, et al. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers- Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Am J Med Genet. Apr 28 1998;77(1):31-7. [Medline].

  8. Voermans NC, van Engelen BG. Differential diagnosis of muscular hypotonia in infants: the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VI). Neuromuscul Disord. Nov 2008;18(11):906; author reply 907. [Medline].

  9. Bar-Yosef O, Polak-Charcon S, Hoffman C, Feldman ZP, Frydman M, Kuint J. Multiple congenital skull fractures as a presentation of Ehlers-Danlos syndrome type VIIC. Am J Med Genet A. Dec 1 2008;146A(23):3054-7. [Medline].

  10. Giunta C, Elcioglu NH, Albrecht B, et al. Spondylocheiro dysplastic form of the Ehlers-Danlos syndrome--an autosomal-recessive entity caused by mutations in the zinc transporter gene SLC39A13. Am J Hum Genet. Jun 2008;82(6):1290-305. [Medline].

  11. Mataix J, Banuls J, Munoz C, et al. Periodontal Ehlers-Danlos syndrome associated with type III and I collagen deficiencies. Br J Dermatol. Apr 2008;158(4):825-30. [Medline].

  12. Juul-Kristensen B, Rogind H, Jensen DV, et al. Inter-examiner reproducibility of tests and criteria for generalized joint hypermobility and benign joint hypermobility syndrome. Rheumatology (Oxford). Dec 2007;46(12):1835-41. [Medline].

  13. Gotte M, Spillmann D, Yip GW, et al. Changes in heparan sulfate are associated with delayed wound repair, altered cell migration, adhesion and contractility in the galactosyltransferase I (beta4GalT-7) deficient form of Ehlers-Danlos syndrome. Hum Mol Genet. Apr 1 2008;17(7):996-1009. [Medline].

  14. Molloy ES, Langford CA. Vasculitis mimics. Curr Opin Rheumatol. Jan 2008;20(1):29-34. [Medline].

  15. Zilocchi M, Macedo TA, Oderich GS, et al. Vascular Ehlers-Danlos syndrome: imaging findings. AJR Am J Roentgenol. Sep 2007;189(3):712-9. [Medline].

  16. Giunta C, Chambaz C, Pedemonte M, Scapolan S, Steinmann B. The arthrochalasia type of Ehlers-Danlos syndrome (EDS VIIA and VIIB): the diagnostic value of collagen fibril ultrastructure. Am J Med Genet A. May 15 2008;146A(10):1341-6. [Medline].

  17. Faber P, Craig WL, Duncan JL, et al. The successful use of recombinant factor VIIa in a patient with vascular-type Ehlers-Danlos syndrome. Acta Anaesthesiol Scand. Oct 2007;51(9):1277-9. [Medline].

  18. Mast KJ, Nunes ME, Ruymann FB, Kerlin BA. Desmopressin responsiveness in children with Ehlers-Danlos syndrome associated bleeding symptoms. Br J Haematol. Jan 2009;144(2):230-3. [Medline].

  19. [Guideline] Rice SG. Medical conditions affecting sports participation. Pediatrics. Apr 2008;121(4):841-8. [Medline].

  20. Leistritz DF, Pepin MG, Schwarze U, Byers PH. COL3A1 haploinsufficiency results in a variety of Ehlers-Danlos syndrome type IV with delayed onset of complications and longer life expectancy. Genet Med. Aug 2011;13(8):717-22. [Medline].

  21. Yis U, Dirik E, Chambaz C, et al. Differential diagnosis of muscular hypotonia in infants: the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VI). Neuromuscul Disord. Mar 2008;18(3):210-4. [Medline].

  22. Esaka EJ, Golde SH, Stever MR, Thomas RL. A maternal and perinatal mortality in pregnancy complicated by the kyphoscoliotic form of Ehlers-Danlos syndrome. Obstet Gynecol. Feb 2009;113(2 Pt 2):515-8. [Medline].

  23. Agnew P. Evaluation of the child with ligamentous laxity. Clin Podiatr Med Surg. Jan 1997;14(1):117-30. [Medline].

  24. Bristow J, Carey W, Egging D, et al. Tenascin-X, collagen, elastin, and the Ehlers-Danlos syndrome. Am J Med Genet C Semin Med Genet. Nov 15 2005;139C(1):24-30. [Medline].

  25. Burrows NP. The molecular genetics of the Ehlers-Danlos syndrome. Clin Exp Dermatol. Mar 1999;24(2):99-106. [Medline].

  26. Egging DF, van Vlijmen-Willems I, Choi J, et al. Analysis of obstetric complications and uterine connective tissue in tenascin-X-deficient humans and mice. Cell Tissue Res. Jun 2008;332(3):523-32. [Medline].

  27. Freeman RK, Swegle J, Sise MJ. The surgical complications of Ehlers-Danlos syndrome. Am Surg. Oct 1996;62(10):869-73. [Medline].

  28. Golfier F, Peyrol S, Attia-Sobol J, et al. Hypermobility type of Ehlers-Danlos syndrome: influence of pregnancies. Clin Genet. Sep 2001;60(3):240-1. [Medline].

  29. Grahame R. Joint hypermobility and genetic collagen disorders: are they related?. Arch Dis Child. Feb 1999;80(2):188-91. [Medline].

  30. Hermanns-Le T, Pierard GE. Multifaceted dermal ultrastructural clues for Ehlers-Danlos syndrome with arterial rupture and type I collagen R-to-C substitution. Am J Dermatopathol. Oct 2007;29(5):449-51. [Medline].

  31. Loeys BL, Chen J, Neptune ER, et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. Mar 2005;37(3):275-81. [Medline].

  32. Malfait F, Symoens S, De Backer J, et al. Three arginine to cysteine substitutions in the pro-alpha (I)-collagen chain cause Ehlers-Danlos syndrome with a propensity to arterial rupture in early adulthood. Hum Mutat. Apr 2007;28(4):387-95. [Medline].

  33. Maltz SB, Fantus RJ, Mellett MM, et al. Surgical complications of Ehlers-Danlos syndrome type IV: case report and review of the literature. J Trauma. Aug 2001;51(2):387-90. [Medline].

  34. Mao JR, Bristow J. The Ehlers-Danlos syndrome: on beyond collagens. J Clin Invest. May 2001;107(9):1063-9. [Medline].

  35. McDowell G, Gahl WA. Inherited disorders of glycoprotein synthesis: cell biological insights. Proc Soc Exp Biol Med. Jun 1997;215(2):145-57. [Medline].

  36. Pepin M, Schwarze U, Superti-Furga A, et al. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med. Mar 9 2000;342(10):673-80. [Medline].

  37. Ploeckinger B, Ulm MR, Chalubinski K. Ehlers-Danlos syndrome type II in pregnancy. Am J Perinatol. Feb 1997;14(2):99-101. [Medline].

  38. Pope FM, Burrows NP. Ehlers-Danlos syndrome has varied molecular mechanisms. J Med Genet. May 1997;34(5):400-10. [Medline].

  39. Raff ML, Byers PH. Joint hypermobility syndromes. Curr Opin Rheumatol. Sep 1996;8(5):459-66. [Medline].

  40. Sareli AE, Janssen WJ, Sterman D, et al. Clinical problem-solving. What's the connection? - A 26-year-old white man presented to our referral hospital with a 1-month history of persistent cough productive of white sputum, which was occasionally tinged with blood. N Engl J Med. Feb 7 2008;358(6):626-32. [Medline].

  41. Schievink WI. Genetics and aneurysm formation. Neurosurg Clin N Am. Jul 1998;9(3):485-95. [Medline].

  42. Schmitz R, Dufty JW, De P. Absence of a sharp glass transition in mode coupling theory. Phys Rev Lett. Sep 27 1993;71(13):2066-2069. [Medline].

  43. Solomon JA, Abrams L, Lichtenstein GR. GI manifestations of Ehlers-Danlos syndrome. Am J Gastroenterol. Nov 1996;91(11):2282-8. [Medline].

  44. Thomas DM, Wright JL, Soucek S, et al. Ehlers-Danlos syndrome: aural manifestations and treatment. Am J Otolaryngol. Nov-Dec 1996;17(6):432-3. [Medline].

  45. Wenstrup RJ, Meyer RA, Lyle JS, et al. Prevalence of aortic root dilation in the Ehlers-Danlos syndrome. Genet Med. May-Jun 2002;4(3):112-7. [Medline].

 
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Patient with Ehlers-Danlos syndrome. Note the abnormal ability to elevate the right toe. Courtesy of Enrico Ceccolini, MD.
Girl with Ehlers-Danlos syndrome. Dorsiflexion of all the fingers is easy and absolutely painless. Courtesy of Enrico Ceccolini, MD.
Patient with Ehlers-Danlos syndrome mitis. Joint hypermobility is less intense than with other conditions. Courtesy of Enrico Ceccolini, MD.
Table 1. Types of Ehlers-Danlos Syndromes[7]
TypeInheritancePrevious NomenclatureMajor Diagnostic CriteriaMinor Diagnostic Criteria
ClassicAutosomal dominantTypes I and IISkin hyperextensibility,



wide atrophic scars, joint hypermobility



Smooth, velvety skin; easy bruising; molluscoid pseudotumors; subcutaneous spheroids; joint hypermobility; muscle hypotonia; postoperative complication (eg, hernia); positive family history; manifestations of tissue fragility (eg, hernia, prolapse)
HypermobilityAutosomal dominantType IIISkin involvement (soft, smooth and velvety), joint hypermobilityRecurrent joint dislocation; chronic joint pain, limb pain, or both; positive family history
VascularAutosomal dominantType IVThin, translucent skin; arterial/intestinal fragility or rupture; extensive bruising; characteristic facial appearanceAcrogeria,



hypermobile small joints; tendon/muscle rupture; clubfoot; early onset varicose veins; arteriovenous, carotid-cavernous sinus fistula;



pneumothorax;



gingival recession; positive family history; sudden death in close relative



KyphoscoliosisAutosomal recessive Type VI – lysyl hydroxylase deficiencyJoint laxity, severe hypotonia at birth, scoliosis, progressive scleral fragility or rupture of globeTissue fragility,



easy bruising, arterial rupture,



marfanoid,



microcornea,



osteopenia,



positive family



history (affected sibling)



ArthrochalasiaAutosomal dominantType VII A, BCongenital bilateral dislocated hips,



severe joint hypermobility,



recurrent subluxations



Skin hyperextensibility,



tissue fragility with atrophic scars, muscle hypotonia,



easy bruising,



kyphoscoliosis, mild osteopenia



DermatosparaxisAutosomal recessiveType VII CSevere skin fragility; saggy, redundant skinSoft, doughy skin;



easy bruising; premature rupture of membranes; hernias (umbilical and inguinal)



Table 2. Molecular Basis of Ehlers-Danlos Syndrome
TypeOld NomenclatureProtein AbnormalityGene AbnormalityChromosome Locus
ClassicType I/IIType V collagenCOL5A1,COL5A29q34.2-34.3



2q31



HypermobilityType IIIUnknownUnknownUnknown
VascularType IVType III collagenCOL3A12q31
KyphoscoliosisType VILysyl hydroxylase deficiency (some)PLOD11p36.3-36.2
ArthrochalasiaType VII A/BType I collagenCOL1A1



COL1A2



17q31-22.5



7q22.1



DermatosparaxisType VIICN-proteinaseADAMST25q23-24
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