Benign joint hypermobility syndrome (BJHS)

Hypermobily type Ehlers-Danlos syndrome (hEDS) is the most common subtype of the Ehlers-Danlos syndromes (EDS) and possibly the most common of all hereditary disorders of connective tissue (HDCT) (1)

• new EDS classification system replaces the diagnosis of Ehlers-Danlos syndrome Type III/ Ehlers-Danlos syndrome Hypermobility Type (EDS-III / EDS-HT) and joint hypermobility syndrome (JHS)
  
  
• many people who were previously assigned a diagnosis of EDS-III, EDS-HT, or JHS will meet the criteria for hEDS
  • others will instead be classed as having Hypermobility Spectrum Disorders (HSD)

Prevalence of hEDS:

• EDS occurs in at least 1 in 5000 of the population, 80-90% of which could be cases of hEDS (1)

Genetics:

• no single gene mutation causing hEDS has been identified
  • likely to be caused by many different genetic changes
• considered to be inherited in a autosomal dominant pattern - however the pattern of inheritance may vary within families and there may be variable penetrance
  • "best way to describe hEDS is as an autosomal dominant disorder influenced by age and gender, with symptoms more common in females" (1)

Diagnostic criteria:

• clinical diagnosis of hEDS needs the simultaneous presence of criteria of:
  
  
  • Generalized joint hypermobility (GJH); and
    
    
  • Two or more of the following features must be present (A & B, A & C, B & C, or A & B & C):
    • Feature A - systemic manifestations of a more generalized connective tissue disorder (a total of five out of twelve must be present)
    • Feature B - positive family history, with one or more first degree relatives independently meeting the current diagnostic criteria for hEDS
    • Feature C - musculoskeletal complications (must have at least one of three); and
      
      
  • also all these prerequisites must be met:
    
    
    • 1) absence of unusual skin fragility, which should prompt consideration of other types of EDS
      
      
    • 2) exclusion of other heritable and acquired connective tissue disorders, including autoimmune rheumatologic conditions. In patients with an acquired CTD (e.g. Lupus, Rheumatoid Arthritis, etc.), additional diagnosis of hEDS requires meeting both Features A and B of Criterion 2. Feature C of Criterion 2 (chronic pain and/or instability) cannot be counted toward a diagnosis of hEDS in this situation
      
      
    • 3) exclusion of alternative diagnoses that may also include joint hypermobility by means of hypotonia and/or connective tissue laxity. Alternative diagnoses and diagnostic categories include, but are not limited to, neuromuscular disorders (e.g. Bethlem myopathy), other hereditary disorders of the connective tissue (e.g. other types of EDS, Loeys-Dietz syndrome, Marfan syndrome), and skeletal dysplasias (e.g. osteogenesis imperfecta). Exclusion of these considerations may be based upon history, physical examination, and/or molecular genetic testing, as indicated.
      

Associated conditions:

• a range of conditions which can accompany hEDS
  • not specific enough to be criteria for diagnosis - include sleep disturbance, fatigue, postural orthostatic tachycardia, functional gastrointestinal disorders, dysautonomia, anxiety, and depression (1)

Detailed notes:

• Criterion 1: Generalized joint hypermobility (GJH)
  • The Beighton score:
    • >= 6 for pre - pubertal children and adolescents,
    • >= 5 for pubertal men and women up to the age of 50, and
    • >= 4 for those >50 years of age for hEDS
      
      
• Criterion 2:
  • Two or more among the following features A, B and C MUST be present (for example: A and B; A and C; B and C; A and B and C)
    
    
    • Feature A: systemic manifestations of a more generalized connective tissue disorder (a total of five must be present)
      • 1. Unusually soft or velvety skin
      • 2. Mild skin hyperextensibility
      • 3. Unexplained striae such as striae distensae or rubrae at the back, groins, thighs, breasts and/or abdomen in adolescents, men or prepubertal women without a history of significant gain or loss of body fat or weight
      • 4. Bilateral piezogenic papules of the heel
      • 5. Recurrent or multiple abdominal hernia(s) (e.g., umbilical, inguinal, crural)
      • 6. Atrophic scarring involving at least two sites and without the formation of truly papyraceous and/or hemosideric scars as seen in classical EDS
      • 7. Pelvic floor, rectal, and/or uterine prolapse in children, men or nulliparous women without a history of morbid obesity or other known predisposing medical condition
      • 8. Dental crowding and high or narrow palate
      • 9. Arachnodactyly, as defined in one or more of the following:
        • a. positive wrist sign (Steinberg sign) on both sides;
        • b. positive thumb sign (Walker sign) on both sides
      • 10. Arm span-to-height >=1.05
      • 11. Mitral valve prolapse (MVP) mild or greater based on strict echocardiographic criteria
      • 12. Aortic root dilatation with Z-score >+2
        
        
    • Feature B: positive family history, with one or more first degree relatives (biological mother, father, brother, sister) independently meeting the current diagnostic criteria for hEDS
      
      
    • Feature C: musculoskeletal complications (must have at least one)
      • 1. Musculoskeletal pain in two or more limbs, recurring daily for at least 3 months
      • 2. Chronic, widespread pain for >=3 months
      • 3. Recurrent joint dislocations or frank joint instability, in the absence of trauma (a or b)
        • a. Three or more atraumatic dislocations in the same joint or two or more atraumatic dislocations in two different joints occurring at different times
        • b. Medical confirmation of joint instability at 2 or more sites not related to trauma
          
          
• Criterion 3: all the following prerequisites MUST be met
  • 1. Absence of unusual skin fragility, which should prompt consideration of other types of EDS
  • 2. Exclusion of other heritable and acquired connective tissue disorders, including autoimmune rheumatologic conditions. In patients with an acquired connective tissue disorder (e.g., lupus, rheumatoid arthritis, etc.), additional diagnosis of hEDS requires meeting both Features A and B of Criterion 2. Feature C of Criterion 2 (chronic pain and/or instability) cannot be counted

Reference:

• The Ehlers-Danlos Society. EDS Types (Accessed June 11th 2018)
• The Ehlers-Danlos Society. Hypermobile Ehlers-Danlos Syndrome: Clinical Description and Natural History (for Non-experts) (Accessed June 11th 2018)