Ehlers-Danlos Syndrome

1. Pathophysiology
   1. Conective tissue disorder
2. Types
   1. Classic Ehlers-Danlos Syndrome (COL5A1, COL5A2, COL1A1; Autosomal Dominant)
      1. Skin Hyperextensibility
      2. Atrophic Scarring
      3. Generalized joint hypermobility
   2. Classic-Like Ehlers-Danlos Syndrome (TNXB, Autosomal Recessive)
      1. Atrophic Scarring absent
   3. Cardiac-Valvular Ehlers-Danlos Syndrome (COL1A2, Autosomal Recessive)
      1. Severe progressive cardiac valvular disorders
   4. Hypermobile Ehlers-Danlos Syndrome (Autosomal Dominant)
      1. Scarring is mild (and no hemosiderotic scars)
      2. Skin is not as fragile
   5. Arthrochalasia Ehlers-Danlos Syndrome (COL1A1, COL1A2; Autosomal Dominant)
      1. Bilateral Congenital Hip Dislocation
   6. Dermatosparaxis Ehlers-Danlos Syndrome (ADAMTS2, Autosomal Recessive)
      1. Significant skin fragility
      2. Redundant lax skin
      3. Craniofacial anomalies
      4. Postnatal growth restriction
   7. Kyphoscoliotic Ehlers-Danlos Syndrome (PLOD1, Autosomal Recessive)
      1. Congenital muscle hypotonia
   8. Kyphoscoliotic Ehlers-Danlos Syndrome with Myopathy and neurosensory Hearing Loss (FKBP14, Autosomal Recessive)
      1. Congenital muscle hypotonia
      2. Muscle Atrophy
      3. Congenital Hearing Deficit
3. Exam: Classic Ehlers-Danlos Syndrome
   1. Skin
      1. Soft dough-like feel
      2. Hyperextensible
      3. Fragile (splits easily with minor Trauma)
         1. Joint surfaces (e.g. knees, elbows)
         2. Trauma prone regions (e.g. chin, shins)
      4. Poor Wound Healing (with scar Stretching)
      5. Easy Bruising
   2. Joints
      1. Hypermobile
      2. Dislocations are common (e.g. Shoulder, Patella, fingers, hip, radius, clavicle)
         1. Often relocated by the patient without medical assistance
   3. Neurologic
      1. Hypotonia
      2. Delayed motor development
      3. Muscle Fatigue
      4. Myalgias
   4. Cardiovascular
      1. Mitral Valve Prolapse (uncommon, and typically benign)
      2. Aortic root dilation (uncommon, and typically static)
4. Diagnosis: Classic Ehlers-Danlos Syndrome
   1. Major Criteria
      1. Skin hyperextensibility AND
      2. Atrophic Scarring AND
      3. Generalized joint hypermobility OR 3 minor criteria
   2. Minor Criteria (3 required if absence of Generalized joint hypermobility)
      1. Easy Bruising
      2. Soft doughy skin
      3. Skin fragility or Traumatic splitting
      4. Molluscoid pseudotumors
         1. Elevated lesions over scarred pressure points (e.g. elbows, knees)
      5. Subcutaneous spheroids
         1. Small round hard densities mobile and palpable within the skin of the forarm or shin
      6. Hernia
      7. Epicanthal Folds
      8. Joint hypermobility complications (sprains, dislocations, flexible flat foot)
      9. First degree relative with Ehlers-Danlos Syndrome diagnostic criteria met
   3. Genetic Confirmation (panel)
      1. COL5A1
      2. COL5A2
      3. COL1A1 (less common)
5. Differential Diagnosis
   1. See Hypermobility syndrome
   2. See types as above
6. Imaging
   1. Echocardiogram
      1. Indicated for aortic dilation or Mitral Valve Prolapse
      2. Repeat yearly, if anomaly present
7. Management
   1. General
      1. Avoid Aspirin
      2. Avoid Contact Sports
   2. Hypotonia or delayed motor development
      1. Physiotherapy
      2. Pool Exercise and other non-weight bearing activities
   3. Joint Pain
      1. NSAIDs
   4. Skin Wounds
      1. Close with two layers, and generous deep Sutures to reduce skin tension
      2. Skin protection (knee pads, shin pads or stockings)
   5. Bruising
      1. Vitamin C supplementation may reduce Bruising
   6. Bleeding complications
      1. Consider DDAVP
8. Prevention: Genetic Counseling
   1. At least 50% of Ehlers-Danlos Syndrome patients have an affected parent (remainder are de novo)
      1. Known parent with Classic Ehlers-Danlos Syndrome (EDS) has a 50% chance of a child with EDS
9. References
   1. Malfait in Adam (2018) Classic Ehlers Danlos Syndrome, GeneReviews
      1. https://www.ncbi.nlm.nih.gov/books/NBK1244/