Handbook of Genetic Counseling/Ehlers-Danlos Syndrome

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Ehlers-Danlos Syndrome


  • Introductions, acknowledge any prior contact
  • Assess main concerns of patient
    • Why are they visiting Genetics today?
    • What do they hope to gain from the session?
    • Assess knowledge of diagnosis -- any questions?
  • Overview of today's session
    • Restate patient's concerns
    • Medical history, family history, physical exam, genetics, recurrence risk, testing options and limitations

Pediatric Intake[edit]

  • Pregnancy and Medical History
    • umbilical/unguinal hernia? prematurity? cervical incompetence?
  • Developmental History
    • learning disabilities?
  • Family History
    • heart problems? joint hypermobility? stretchy skin? fragile skin? easy to scar? scoliosis? easy bruising? congenital hip dislocations? stroke? umbilical/inguinal hernias? early loss of teeth?

Incidence and Carrier Frequency[edit]

  • no well-founded figures for prevalence
  • for all forms, estimates of 1/5000 have been made

Clinical Features[edit]

    • a group of clinically diverse inherited connective tissue disorders that

have joint laxity and dermal features in common **

  • Classical (Type I and Type II)
    • Major diagnostic criteria
      • Hyperextensibility of the skin
      • Widened atrophic scars
      • Joint hypermobility
        • Can lead to osteoarthritis in the 3rd or 4th decade
    • Other features
      • Poor wound healing
      • ½ of affected individuals are delivered up to 1 month premature due to premature rupture of fetal membranes
      • Some have cardiac abnormalities
        • Mitral valve prolapse
        • Aortic root dilation with occasional rupture
      • Scoliosis
      • Pes planus (flatfoot)
      • Molluscoid pseudotumors (calcified hematomas) may be associated with scars
    • Inheritance
      • Autosomal dominant single-gene disorder
    • Etiology
      • A major cause is mutations in type V collagen
      • At least 3 loci are involved
    • Biochemical Defects
      • Thickened collagen fibrils in skin as well as "cauliflower" deformities of collagen fibrils
      • Mutations in COL5A1 and COL5A2 have been seen in some families
    • Testing
      • No biochemical or molecular based testing methods have been devised to provide reliable results
  • Hypermobility Type (Type III)
    • Primary characteristics
      • Hyperextensibility of large and small joints
      • Soft, velvety skin
    • Other features
      • May have normal scarring but stretchy skin
      • Dilatation and/or rupture of the ascending aorta
      • Scoliosis
      • Pes planus
    • Inheritance
      • Autosomal dominant single-gene disorder
    • Diagnosis is clinical
  • Vascular Type (Type IV)
    • Major diagnostic criteria
      • Characteristic facial appearance
      • Thin, delicate, "pinched" nose
      • Thick lips
      • Hollow cheeks
      • Some have staring appearance due to decreased adipose tissue below the eyes
      • Thin, translucent skin
        • In fair-skinned individuals, subcutaneous vasculature is easily visible beneath the skin
      • Arterial/intestinal/uterine fragility or rupture which can be life threatening
      • Extensive bruising
    • Other characteristics
      • Normal scar formation
      • May be increased incidence of stroke
      • Acrogeria (aged appearance to extremities, particularly hands)
      • ¼ of affected individuals experience a significant medical problem by age 20
      • Median age of death is 48 years old
    • Inheritance
      • Autosomal dominant as demonstrated by linkage analysis
    • Etiology (COL3A1 gene)
      • Dominant mutations in the gene for the pro-alpha 1 chain of type II collagen
      • Caused by abnormal synthesis, structure, or secretion of type II collagen
      • 50% have new disease-causing mutations
      • Over 250 COL3A1 disease-causing mutations have been found
    • Testing
      • Can be reliably accomplished by analysis of type III procollagen and collagen chains harvested from cultured dermal fibroblasts
  • Kyphoscoliosis type (type VI)
    • Key features
      • Neonatal onset of joint laxity
      • Kyphoscoliosis (lateral curvature of the spine accompanying an anteroposterior hump)
      • Muscle hypotonia
    • Other features
      • Ocular fragility
      • Skin fragility
      • Easy bruisability
      • Dermal hyperextensibility
      • Risk for arterial rupture
      • Most have radiologically detectable osteopenia (decreased bone density), but pathological fractures are rare
      • Intelligence is normal
      • Lifespan may be normal
    • Etiology
      • Caused by deficient activity of the enzyme procollagen lysine hydroxylase
    • Inheritance
      • Autosomal recessive
    • Testing
      • Diagnosis depends on demonstration of increased ratio of deoxypyridinoline to pyridinoline crosslinks in urine measured by HPLC
      • Mutation analysis of the PLOD gene that encodes the enzyme procollagen lysine hydroxylase is available on a research basis
      • Carrier testing is not available
  • Arthrochalasia type (types VIIA, VIIB)
    • Major criteria
      • Severe generalized joint hypermobility
      • Congenital bilateral hip dislocations that are difficult to repair surgically
    • Other features
      • Tissue fragility including atrophic scars
      • Kyphoscoliosis
      • Skin hyperextensibility
    • Etiology
      • Caused by a failure to accomplish normal cleavage of the amino-terminal propeptide of type I collagen in all tissues
      • Mutations that remove exon 6 in COL1A1 and COL1A2 are seen
    • Inheritance
      • Autosomal dominant
    • Testing
      • Demonstration of exon 6 skipping in cDNAs of COL1A1 or COL1A2 followed by mutational analysis
  • Dermatosporaxis type (type VIIC)
    • Very rare form of EDS
    • Diagnostic Features
      • Dermal fragility: the skin is lax but not stretchy
    • Other features
      • Joint dislocation is usually not a feature
      • Infants have been reported with premature rupture of membranes and umbilical/inguinal hernias
    • Etiology
      • Caused by failure to cleave off the amino-terminal propeptide of type I collagen due to deficiency of the procolagen I N-peptidase gene
    • Inheritance
      • Autosomal recessive
  • Other variants (VIII, V X-linked, X)
    • Type VIII
      • Rare autosomal dominant condition
      • Characterized by soft, hyperextensible skin, abnormal scarring, easy bruising, hyperextensible joints and generalized periodontitis
      • Resembles type I, but is distinguished by early loss of teeth and characteristic purplish discoloration of scars on the shins
      • Molecular basis is unknown
      • Not clear if it is truly distinct from classical form
    • Type V X-linked
      • Similar to mild classical type
      • X-linked recessive inheritance
      • Unknown molecular defect
    • Type X
      • Joint hyperextensibility, mitral valve prolapse, easy bruising, poor wound healing, clotting disorder
      • Clotting studies showed a defect in the platelet adhesion that is normally observed in response to exposure of platelets to collagen
      • May be caused by a defect in fibronectin

Management and Treatment[edit]

  • Pregnancy
    • All cases should be referred to high-risk obstetric practice
    • Prematurity is a concern
    • Cervical incompetence can be treated with bed rest and the Trendelenburg position
  • Musculoskeletal
    • P/T can improve strength of muscles surrounding lax joints
    • Surgical procedures can correct dislocation
    • Intervention for pain management is necessary
    • An exercise program can strengthen muscles and stabilize joints
  • Cardiovascular
    • Enlarged aortic root can be treated with beta blockers but the efficacy or length of treatment is currently unknown
    • Exercise limitation may be necessary, especially competitive sports
    • Surgical complications and intraoperative problems are common
  • Dermatologic
    • Plastic surgery can be done to close facial wounds or other aesthetically significant areas
    • Retention sutures tied at a distance from the incision may help support the skin during scar formation

Psychosocial Issues[edit]

  • Self esteem
    • scars, bruising, scoliosis
  • Financial concerns?
  • Guilt at passing on mutation
  • Pain management issues
  • support network?
    • family? friends? church?

Support Groups and Resources[edit]

  • Ehlers-Danlos National Foundation
  • Ehlers-Danlos Support Group
  • Family Village


  • www.geneclinics.org
  • Management of Genetic Syndromes (Allanson and Cassidy)
  • OMIM #130000, #130010, #130020, #130050, #305200, #225400, #130060, #130080


The information in this outline was last updated in 2002.