Genetics of Ehlers-Danlos Syndrome Workup

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

Laboratory Studies

The following laboratory studies may be indicated in patients with Ehlers-Danlos syndrome (EDS):

  • To confirm the diagnosis of the vascular form (type IV) of Ehlers-Danlos syndrome and for arthrochalasia (Ehlers-Danlos syndrome type VIIA and VIIB) and dermatosparaxis (Ehlers-Danlos syndrome VIIC), biochemical studies can detect alterations in collagen molecules in cultured skin fibroblasts.
  • Molecular (DNA-based) testing is available for Ehlers-Danlos syndrome types IV and VII as well.
  • With the exception of kyphoscoliotic type (Ehlers-Danlos syndrome type VI), which can be identified by urinary analyte assay, the most common and remaining forms of Ehlers-Danlos syndrome are identified by clinical examination.
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Imaging Studies

Zilocchi et al reviewed imaging findings in vascular Ehlers-Danlos syndrome.[15] Using CT scanning, MRI, ultrasonography, and angiography, the most common findings were arterial aneurysms and arterial dissections, followed by arterial ectasias and arterial occlusions.

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Other Tests

Ultrastructural examination of collagen fibrils may be a useful additional diagnostic tool, for supporting the diagnosis of the classical form of Ehlers-Danlos syndrome but also for Ehlers-Danlos syndrome type VII and the differentiation into Ehlers-Danlos syndrome type VIIA and Ehlers-Danlos syndrome type VIIB.[16]

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Procedures

Skin biopsy findings (performed for histopathologic analysis) are nondiagnostic.

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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

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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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