Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/ehlers-danlos syndrome hypermobility type compared to other heritable connective tissue disorders

Am J Med Genet C Semin Med Genet. 2015 Mar;169C(1):6-22. doi: 10.1002/ajmg.c.31429.

Abstract

Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is an evolving and protean disorder mostly recognized by generalized joint hypermobility and without a defined molecular basis. JHS/EDS-HT also presents with other connective tissue features affecting a variety of structures and organs, such as skin, eye, bone, and internal organs. However, most of these signs are present in variable combinations and severity in many other heritable connective tissue disorders. Accordingly, JHS/EDS-HT is an "exclusion" diagnosis which needs the absence of any consistent feature indicative of other partially overlapping connective tissue disorders. While both Villefranche and Brighton criteria include such an exclusion as a mandatory item, a systematic approach for reaching a stringent clinical diagnosis of JHS/EDS-HT is still lacking. The absence of a consensus on the diagnostic approach to JHS/EDS-HT concerning its clinical boundaries with similar conditions contribute to limit our actual understanding of the pathologic and molecular bases of this disorder. In this review, we revise the differential diagnosis of JHS/EDS-HT with those heritable connective tissue disorders which show a significant overlap with the former and mostly include EDS classic, vascular and kyphoscoliotic types, osteogenesis imperfecta, Marfan syndrome, Loeys-Dietz syndrome, arterial tortuosity syndrome, and lateral meningocele syndrome. A diagnostic flow chart is also offered with the attempt to support the less experienced clinician in stringently recognizing JHS/EDS-HT and stimulate the debate in the scientific community for both management and research purposes.

Keywords: Ehlers-Danlos syndrome hypermobility type; diagnostic flow chart; differential diagnosis; heritable connective tissue disorders; joint hypermobility syndrome.

Publication types

  • Review

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / physiopathology
  • Arteries / abnormalities*
  • Arteries / physiopathology
  • Connective Tissue Diseases / diagnosis*
  • Connective Tissue Diseases / physiopathology
  • Diagnosis, Differential*
  • Ehlers-Danlos Syndrome / diagnosis*
  • Ehlers-Danlos Syndrome / physiopathology
  • Humans
  • Joint Instability / diagnosis*
  • Joint Instability / physiopathology
  • Loeys-Dietz Syndrome / diagnosis
  • Loeys-Dietz Syndrome / physiopathology
  • Marfan Syndrome / diagnosis
  • Marfan Syndrome / physiopathology
  • Meningocele / diagnosis
  • Meningocele / physiopathology
  • Osteogenesis Imperfecta / diagnosis
  • Osteogenesis Imperfecta / physiopathology
  • Skin Abnormalities / diagnosis
  • Skin Abnormalities / physiopathology
  • Skin Diseases, Genetic / diagnosis*
  • Skin Diseases, Genetic / physiopathology
  • Surveys and Questionnaires
  • Vascular Malformations / diagnosis*
  • Vascular Malformations / physiopathology

Supplementary concepts

  • Arterial Tortuosity Syndrome
  • Ehlers-Danlos syndrome type 3
  • Lateral meningocele syndrome